Sexual differentiation
Encyclopedia
Sexual differentiation is the process of development of the differences between male
s and female
s from an undifferentiated zygote
(fertilized egg
). As male and female individuals develop from zygotes into fetus
es, into infants, children, adolescents, and eventually into adults, sex
and gender
differences at many levels develop: gene
s, chromosome
s, gonad
s, hormone
s, anatomy
, and psyche.
Sex differences range from nearly absolute to simply statistical. Sex-dichotomous differences are developments which are wholly characteristic of one sex only. Examples of sex-dichotomous differences include aspects of the sex-specific genital organs such as ovaries
, a uterus
or a phallic urethra
. In contrast, sex-dimorphic
differences are matters of degree (e.g., size of phallus). Some of these (e.g., stature
, behaviors) are mainly statistical, with much overlap between male and female populations.
Nevertheless, even the sex-dichotomous differences are not absolute in the human population, and there are individuals who are exceptions (e.g., males with a uterus, or females with an XY
karyotype
), or who exhibit biological and/or behavioral characteristics of both sexes.
Sex differences may be induced by specific genes
, by hormones, by anatomy
, or by social learning
. Some of the differences are entirely physical (e.g., presence of a uterus) and some differences are just as obviously purely a matter of social learning and custom (e.g., relative hair length). Many differences, though, such as gender identity
, appear to be influenced by both biological and social factors ("nature" and "nurture"
).
The early stages of human differentiation appear to be quite similar to the same biological processes in other mammals and the interaction of genes, hormones and body structures is fairly well understood. In the first weeks of life, a fetus
has no anatomic or hormonal sex
, and only a karyotype
distinguishes male from female. Specific genes induce gonad
al differences, which produce hormonal differences, which cause anatomic differences, leading to psychological and behavioral differences, some of which are innate and some induced by the social environment
.
The various ways that genes, hormones, and upbringing affect different human behaviors and mental traits are difficult to test experimentally and charged with political conflict.
in females and XY
in males. It is obvious that the Y chromosome
must carry at least one essential gene which determines testicular formation (originally termed TDF). A gene in the sex-determining region of the short arm of the Y, now referred to as SRY
, has been found to direct production of a protein which binds to DNA, inducing differentiation of cells derived from the genital ridges into testes. In transgenic XX mice (and some human XX male
s), SRY alone is sufficient to induce male differentiation.
Investigation of other cases of human sex reversal (XX male
s, XY female
s) has led to discovery of other genes crucial to testicular differentiation on autosome
s (e.g., WT-1, SOX9, SF-1), and the short arm of X (DSS).
s migrate from structures known as yolk sacs to the genital ridge
. By week 6, undifferentiated gonad
s consist of germ cell
s, supporting cells, and steroidogenic cells.
In a male, SRY and other genes induce differentiation of supporting cells into Sertoli cell
s and (indirectly) steroidogenic cells into Leydig cell
s to form testes, which become microscopically identifiable and begin to produce hormones by week 8. Germ cells become spermatogonia
.
Without SRY, ovaries
form during months 2-6. Failure of ovarian development in 45,X girls (Turner syndrome
) implies that two functional copies of several Xp
and Xq
genes are needed. Germ cells become ovarian follicle
s. Supporting and steroidogenic cells become theca cells and granulosa cell
s, respectively.
and protein hormones essential for internal and external anatomic differentiation. Leydig cell
s begin to make testosterone
by the end of month 2 of gestation. From then on, male fetuses have higher levels of androgen
s in their systemic blood than females. The difference is even greater in pelvic and genital tissues. Antimullerian hormone (AMH) is a protein hormone produced by Sertoli cell
s from the 8th week on. AMH suppresses development of müllerian ducts in males, preventing development of a uterus
.
Fetal ovaries produce estradiol
, which supports follicular maturation but plays little part in other aspects of prenatal sexual differentiation, as maternal estrogen floods fetuses of both sexes.
can be seen. However, this is only the external genital differentiation. There is also an internal genital differentiation.
s are histologically distinguishable by 6–8 weeks of gestation. A fetus of that age has both mesonephric (wolffian) and paramesonephric (mullerian) ducts. Subsequent development of one set and degeneration of the other depends on the presence or absence of two testicular hormones: testosterone
and AMH. Disruption of typical development may result in the development of both, or neither, duct system, which may produce morphologically intersexual individuals.
Local testosterone causes each wolffian duct to develop into epididymis
, vas deferens
, and seminal vesicles. Without male testosterone levels, wolffian ducts degenerate and disappear. Müllerian ducts develop into a uterus
, fallopian tube
s, and upper vagina
unless AMH induces degeneration. The presence of a uterus is stronger evidence of absence of testes than the state of the external genitalia.
, urogenital groove and sinus, and labioscrotal folds
. In females, without excess androgens, these become the clitoris
, urethra
and vagina
, and labia.
Males become externally distinct between 8 and 12 weeks, as androgens enlarge the phallus and cause the urogenital groove and sinus to fuse in the midline, producing an unambiguous penis
with a phallic urethra, and a thinned, rugated scrotum
.
A sufficient amount of any androgen can cause external masculinization
. The most potent is dihydrotestosterone
(DHT), generated from testosterone in skin and genital tissue by the action of 5α-reductase. A male fetus may be incompletely masculinized if this enzyme is deficient
. In some disease
s and circumstances, other androgens may be present in high enough concentrations to cause partial or (rarely) complete masculinization of the external genitalia of a genetically female fetus.
Further sex differentiation of the external genitalia occurs at puberty
, when androgen levels again become disparate. Male levels of testosterone directly induce growth of the penis, and indirectly (via DHT) the prostate
.
, when estradiol
and other hormones cause breast
s to develop in girls. However, fetal or neonatal androgens may modulate later breast development by reducing the capacity of breast tissue to respond to later estrogen
.
differs between the sexes. Males have more terminal hair
, especially on the face
, chest
, abdomen
and back, and females have more vellus hair, which is less visible. This may also be linked to neoteny
in humans, as vellus hair is a juvenile characteristic.
creates the secondary sex characteristic
s.
General habitus and shape of body and face, as well as sex hormone levels, are similar in prepubertal boys and girls. As puberty progresses and sex hormone levels rise, obvious differences appear.
In males, testosterone directly increases size and mass of muscles, vocal cords, and bone
s, enhancing strength, deepening the voice, and changing the shape of the face and skeleton. Converted into DHT in the skin, it accelerates growth of androgen-responsive facial and body hair. Taller stature is largely a result of later puberty and slower epiphyseal fusion.
In females, in addition to breast differentiation, estrogen also widens the pelvis
and increases the amount of body fat
in hips, thighs, buttocks, and breasts. Estrogen also induces growth of the uterus, proliferation of the endometrium
, and menses
.
The difference in adult masculine and feminine faces is largely a result of a more prominent chin, heavier jaw and jaw muscle development and thicker orbital eyebrow bossing. Masculine features on average are slightly thicker and coarser. Androgen-induced recession of the male hairline accentuates these differences by middle adult life.
Sexual dimorphism of skeletal structure develops during childhood, and becomes more pronounced at adolescence. Sexual orientation has been demonstrated to correlate with skeletal characters that become dimorphic during early childhood (such as arm length to stature ratio) but not with characters that become dimorphic during puberty (such as shoulder width) (Martin & Nguyen, 2004).
to sex hormones produce significant differences of brain structure and function which correlate with adult reproductive behavior.
This seems to be the case in humans as well; sex hormone levels in male and female fetuses and infants differ, and both androgen receptors and estrogen receptors have been identified in brains. Several sex-specific genes not dependent on sex steroids are expressed differently in male and female human brains. Structural sex differences begin to be recognizable by 2 years of age, and in adult men and women include size and shape of corpus callosum
and certain hypothalamic
nuclei, and the gonadotropin
feedback response to estradiol
.
of biological factors and learning to human psychological and behavioral sex differences (especially gender identity, role, and orientation
) remain unsettled and controversial.
Current theories of mechanisms of sexual differentiation of brain and behaviors in humans are based primarily on three sources of evidence: animal research involving manipulation of hormones in early life, observation of outcomes of small numbers of individuals with disorders of sexual development (intersex
conditions or cases of early sex reassignment
), and statistical distribution of traits in populations (e.g., rates of homosexuality in twins). Many of these cases suggest some genetic or hormonal effect on sex differentiation of behavior and mental traits; others do not.
In addition to affecting development, changing hormone levels affect certain behaviors or traits that are gender dimorphic, such as superior verbal fluency among women.
In most mammal
ian species females are more oriented toward child rearing and males toward competition with other males.
, gender roles and sexual orientation
.
and masculinization are the differentiating processes that a fetus goes through to become male. From this perspective, the female is the default path for a developing human being in that gene actions that are eliminated and that are necessary for formation of male genitalia lead to the development of external female genitalia.
Biologically, this perspective is supported by the fact that there are neither female genes nor female hormones that correspond to the hormones active in males only. Estrogen, for instance, is present in both the male and female fetus.
Male
Male refers to the biological sex of an organism, or part of an organism, which produces small mobile gametes, called spermatozoa. Each spermatozoon can fuse with a larger female gamete or ovum, in the process of fertilization...
s and female
Female
Female is the sex of an organism, or a part of an organism, which produces non-mobile ova .- Defining characteristics :The ova are defined as the larger gametes in a heterogamous reproduction system, while the smaller, usually motile gamete, the spermatozoon, is produced by the male...
s from an undifferentiated zygote
Zygote
A zygote , or zygocyte, is the initial cell formed when two gamete cells are joined by means of sexual reproduction. In multicellular organisms, it is the earliest developmental stage of the embryo...
(fertilized egg
Ovum
An ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...
). As male and female individuals develop from zygotes into fetus
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
es, into infants, children, adolescents, and eventually into adults, sex
Sex
In biology, sex is a process of combining and mixing genetic traits, often resulting in the specialization of organisms into a male or female variety . Sexual reproduction involves combining specialized cells to form offspring that inherit traits from both parents...
and gender
Gender
Gender is a range of characteristics used to distinguish between males and females, particularly in the cases of men and women and the masculine and feminine attributes assigned to them. Depending on the context, the discriminating characteristics vary from sex to social role to gender identity...
differences at many levels develop: gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s, chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s, gonad
Gonad
The gonad is the organ that makes gametes. The gonads in males are the testes and the gonads in females are the ovaries. The product, gametes, are haploid germ cells. For example, spermatozoon and egg cells are gametes...
s, hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s, anatomy
Anatomy
Anatomy is a branch of biology and medicine that is the consideration of the structure of living things. It is a general term that includes human anatomy, animal anatomy , and plant anatomy...
, and psyche.
Sex differences range from nearly absolute to simply statistical. Sex-dichotomous differences are developments which are wholly characteristic of one sex only. Examples of sex-dichotomous differences include aspects of the sex-specific genital organs such as ovaries
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...
, a uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
or a phallic urethra
Urethra
In anatomy, the urethra is a tube that connects the urinary bladder to the genitals for the removal of fluids out of the body. In males, the urethra travels through the penis, and carries semen as well as urine...
. In contrast, sex-dimorphic
Sexual dimorphism
Sexual dimorphism is a phenotypic difference between males and females of the same species. Examples of such differences include differences in morphology, ornamentation, and behavior.-Examples:-Ornamentation / coloration:...
differences are matters of degree (e.g., size of phallus). Some of these (e.g., stature
Height
Height is the measurement of vertical distance, but has two meanings in common use. It can either indicate how "tall" something is, or how "high up" it is. For example "The height of the building is 50 m" or "The height of the airplane is 10,000 m"...
, behaviors) are mainly statistical, with much overlap between male and female populations.
Nevertheless, even the sex-dichotomous differences are not absolute in the human population, and there are individuals who are exceptions (e.g., males with a uterus, or females with an XY
XY sex-determination system
The XY sex-determination system is the sex-determination system found in humans, most other mammals, some insects and some plants . In this system, females have two of the same kind of sex chromosome , and are called the homogametic sex. Males have two distinct sex chromosomes , and are called...
karyotype
Karyotype
A karyotype is the number and appearance of chromosomes in the nucleus of an eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism.p28...
), or who exhibit biological and/or behavioral characteristics of both sexes.
Sex differences may be induced by specific genes
Gênes
Gênes is the name of a département of the First French Empire in present Italy, named after the city of Genoa. It was formed in 1805, when Napoleon Bonaparte occupied the Republic of Genoa. Its capital was Genoa, and it was divided in the arrondissements of Genoa, Bobbio, Novi Ligure, Tortona and...
, by hormones, by anatomy
Anatomy
Anatomy is a branch of biology and medicine that is the consideration of the structure of living things. It is a general term that includes human anatomy, animal anatomy , and plant anatomy...
, or by social learning
Social learning
Social learning may refer to:* Observational learning , learning that occurs as a function of observing, retaining and replicating behavior observed in ones environment or other people....
. Some of the differences are entirely physical (e.g., presence of a uterus) and some differences are just as obviously purely a matter of social learning and custom (e.g., relative hair length). Many differences, though, such as gender identity
Gender identity
A gender identity is the way in which an individual self-identifies with a gender category, for example, as being either a man or a woman, or in some cases being neither, which can be distinct from biological sex. Basic gender identity is usually formed by age three and is extremely difficult to...
, appear to be influenced by both biological and social factors ("nature" and "nurture"
Nature versus nurture
The nature versus nurture debate concerns the relative importance of an individual's innate qualities versus personal experiences The nature versus nurture debate concerns the relative importance of an individual's innate qualities ("nature," i.e. nativism, or innatism) versus personal experiences...
).
The early stages of human differentiation appear to be quite similar to the same biological processes in other mammals and the interaction of genes, hormones and body structures is fairly well understood. In the first weeks of life, a fetus
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
has no anatomic or hormonal sex
Sex
In biology, sex is a process of combining and mixing genetic traits, often resulting in the specialization of organisms into a male or female variety . Sexual reproduction involves combining specialized cells to form offspring that inherit traits from both parents...
, and only a karyotype
Karyotype
A karyotype is the number and appearance of chromosomes in the nucleus of an eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism.p28...
distinguishes male from female. Specific genes induce gonad
Gonad
The gonad is the organ that makes gametes. The gonads in males are the testes and the gonads in females are the ovaries. The product, gametes, are haploid germ cells. For example, spermatozoon and egg cells are gametes...
al differences, which produce hormonal differences, which cause anatomic differences, leading to psychological and behavioral differences, some of which are innate and some induced by the social environment
Society
A society, or a human society, is a group of people related to each other through persistent relations, or a large social grouping sharing the same geographical or virtual territory, subject to the same political authority and dominant cultural expectations...
.
The various ways that genes, hormones, and upbringing affect different human behaviors and mental traits are difficult to test experimentally and charged with political conflict.
Chromosomal sex differences
Humans have forty-six chromosomes, including two sex chromosomes, XXXY sex-determination system
The XY sex-determination system is the sex-determination system found in humans, most other mammals, some insects and some plants . In this system, females have two of the same kind of sex chromosome , and are called the homogametic sex. Males have two distinct sex chromosomes , and are called...
in females and XY
XY sex-determination system
The XY sex-determination system is the sex-determination system found in humans, most other mammals, some insects and some plants . In this system, females have two of the same kind of sex chromosome , and are called the homogametic sex. Males have two distinct sex chromosomes , and are called...
in males. It is obvious that the Y chromosome
Y chromosome
The Y chromosome is one of the two sex-determining chromosomes in most mammals, including humans. In mammals, it contains the gene SRY, which triggers testis development if present. The human Y chromosome is composed of about 60 million base pairs...
must carry at least one essential gene which determines testicular formation (originally termed TDF). A gene in the sex-determining region of the short arm of the Y, now referred to as SRY
SRY
SRY is a sex-determining gene on the Y chromosome in the therians .This intronless gene encodes a transcription factor that is a member of the SOX gene family of DNA-binding proteins...
, has been found to direct production of a protein which binds to DNA, inducing differentiation of cells derived from the genital ridges into testes. In transgenic XX mice (and some human XX male
XX male syndrome
XX male syndrome is a rare sex chromosomal disorder. Usually it is caused by unequal crossing over between X and Y chromosomes during meiosis in the father, which results in the X chromosome containing the normally-male SRY gene...
s), SRY alone is sufficient to induce male differentiation.
Investigation of other cases of human sex reversal (XX male
XX male syndrome
XX male syndrome is a rare sex chromosomal disorder. Usually it is caused by unequal crossing over between X and Y chromosomes during meiosis in the father, which results in the X chromosome containing the normally-male SRY gene...
s, XY female
Swyer syndrome
Swyer syndrome, or XY gonadal dysgenesis, is a type of hypogonadism in a person whose karyotype is 46,XY. The person is externally female with streak gonads, and left untreated, will not experience puberty...
s) has led to discovery of other genes crucial to testicular differentiation on autosome
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
s (e.g., WT-1, SOX9, SF-1), and the short arm of X (DSS).
Timeline
| Fetal age (weeks) |
Crown-rump length (mm) |
Sex differentiating events |
| 0 | blastocyst Blastocyst The blastocyst is a structure formed in the early embryogenesis of mammals, after the formation of the morula. It is a specifically mammalian example of a blastula. It possesses an inner cell mass , or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast,... |
Inactivation of one X chromosome X chromosome The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system... |
| 4 | 2-3 | Development of wolffian duct Wolffian duct The mesonephric duct is a paired organ found in mammals including humans during embryogenesis.... s |
| 5 | 7 | Migration of primordial germ cell Germ cell A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate near the gut of an embryo and migrate to the developing gonads. There, they undergo cell division of two types, mitosis and meiosis, followed by... s in the undifferentiated gonad Gonad The gonad is the organ that makes gametes. The gonads in males are the testes and the gonads in females are the ovaries. The product, gametes, are haploid germ cells. For example, spermatozoon and egg cells are gametes... |
| 6 | 10-15 | Development of müllerian duct Müllerian duct Müllerian ducts are paired ducts of the embryo that run down the lateral sides of the urogenital ridge and terminate at the Müllerian eminence in the primitive urogenital sinus. In the female, they will develop to form the Fallopian tubes, uterus, cervix, and the upper two-third of the vagina; in... s |
| 7 | 13-20 | Differentiation of seminiferous tubules Seminiferous tubules Seminiferous tubules are located in the testes, and are the specific location of meiosis, and the subsequent creation of gametes, namely spermatozoa.... |
| 8 | 30 | Regression of müllerian ducts in male fetus Fetus A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The... |
| 8 | 32-35 | Appearance of Leydig cells. First synthesis of testosterone Testosterone Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands... |
| 9 | 43 | Total regression of müllerian ducts. Loss of sensitivity of müllerian ducts in the female fetus |
| 9 | 43 | First meiotic prophase Prophase Prophase, from the ancient Greek πρό and φάσις , is a stage of mitosis in which the chromatin condenses into a highly ordered structure called a chromosome in which the chromatin becomes visible. This process, called chromatin condensation, is mediated by the condensin complex... in oogonia Oogonium "Oogonium" may refer to either a primordial oocyte in a female fetus or the female gametangium of certain thallophytes.-in the fetus:Oogonia are formed in large numbers by mitosis early in fetal development from primordial germ cells... |
| 10 | 43-45 | Beginning of masculinization Virilization In biology and medicine, virilization refers to the biological development of sex differences, changes that make a male body different from a female body. Most of the changes of virilization are produced by androgens... of external genitalia Sex organ A sex organ, or primary sexual characteristic, as narrowly defined, is any of the anatomical parts of the body which are involved in sexual reproduction and constitute the reproductive system in a complex organism; flowers are the reproductive organs of flowering plants, cones are the reproductive... |
| 10 | 50 | Beginning of regression of wolffian ducts in the female fetus |
| 12 | 70 | Fetal testis Testicle The testicle is the male gonad in animals. Like the ovaries to which they are homologous, testes are components of both the reproductive system and the endocrine system... is in the internal inguinal ring |
| 12-14 | 70-90 | Male penile urethra Urethra In anatomy, the urethra is a tube that connects the urinary bladder to the genitals for the removal of fluids out of the body. In males, the urethra travels through the penis, and carries semen as well as urine... is completed |
| 14 | 90 | Appearance of first spermatogonia Spermatogonium A spermatogonium is an intermediary male gametogonium in the production of spermatozoa.There are three subtypes:... |
| 16 | 100 | Appearance of first ovarian follicles |
| 17 | 120 | Numerous Leydig cells. Peak of testosterone secretion |
| 20 | 150 | Regression of Leydig cells. Diminished testosterone secretion |
| 24 | 200 | First multilayered ovarian follicles. Canalisation of the vagina |
| 28 | 230 | Cessation of oogonia multiplication |
| 28 | 230 | Descent of testis |
- Reference: PC Sizonenko in Pediatric Endocrinology, edited by J. Bertrand, R. Rappaport, and PC Sizonenko, (Baltimore: Williams & Wilkins, 1993), pp. 88–99.
Gonadal differentiation
Early in fetal life, germ cellGerm cell
A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate near the gut of an embryo and migrate to the developing gonads. There, they undergo cell division of two types, mitosis and meiosis, followed by...
s migrate from structures known as yolk sacs to the genital ridge
Gonadal ridge
In embryology, the gonadal ridge is the precursor to the gonads. The gonadal ridge initially consists mainly of mesenchyme and cells of underlying mesonephric origin. Once oogonia enter this area they attempt to associate with these somatic cells...
. By week 6, undifferentiated gonad
Gonad
The gonad is the organ that makes gametes. The gonads in males are the testes and the gonads in females are the ovaries. The product, gametes, are haploid germ cells. For example, spermatozoon and egg cells are gametes...
s consist of germ cell
Germ cell
A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate near the gut of an embryo and migrate to the developing gonads. There, they undergo cell division of two types, mitosis and meiosis, followed by...
s, supporting cells, and steroidogenic cells.
In a male, SRY and other genes induce differentiation of supporting cells into Sertoli cell
Sertoli cell
A Sertoli cell is a 'nurse' cell of the testes that is part of a seminiferous tubule.It is activated by follicle-stimulating hormone and has FSH-receptor on its membranes.-Functions:...
s and (indirectly) steroidogenic cells into Leydig cell
Leydig cell
Leydig cells, also known as interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle. They produce testosterone in the presence of luteinizing hormone...
s to form testes, which become microscopically identifiable and begin to produce hormones by week 8. Germ cells become spermatogonia
Spermatogonium
A spermatogonium is an intermediary male gametogonium in the production of spermatozoa.There are three subtypes:...
.
Without SRY, ovaries
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...
form during months 2-6. Failure of ovarian development in 45,X girls (Turner syndrome
Turner syndrome
Turner syndrome or Ullrich-Turner syndrome encompasses several conditions in human females, of which monosomy X is most common. It is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent...
) implies that two functional copies of several Xp
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
and Xq
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
genes are needed. Germ cells become ovarian follicle
Ovarian follicle
Ovarian follicles are the basic units of female reproductive biology, each of which is composed of roughly spherical aggregations of cells found in the ovary. They contain a single oocyte . These structures are periodically initiated to grow and develop, culminating in ovulation of usually a single...
s. Supporting and steroidogenic cells become theca cells and granulosa cell
Granulosa cell
A granulosa cell or follicular cell is a somatic cell of the sex cord that is closely associated with the developing female gamete in the ovary of mammals.-Anatomy and function:...
s, respectively.
Hormonal differentiation
In a male fetus, testes produce steroidSteroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...
and protein hormones essential for internal and external anatomic differentiation. Leydig cell
Leydig cell
Leydig cells, also known as interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle. They produce testosterone in the presence of luteinizing hormone...
s begin to make testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
by the end of month 2 of gestation. From then on, male fetuses have higher levels of androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
s in their systemic blood than females. The difference is even greater in pelvic and genital tissues. Antimullerian hormone (AMH) is a protein hormone produced by Sertoli cell
Sertoli cell
A Sertoli cell is a 'nurse' cell of the testes that is part of a seminiferous tubule.It is activated by follicle-stimulating hormone and has FSH-receptor on its membranes.-Functions:...
s from the 8th week on. AMH suppresses development of müllerian ducts in males, preventing development of a uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
.
Fetal ovaries produce estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
, which supports follicular maturation but plays little part in other aspects of prenatal sexual differentiation, as maternal estrogen floods fetuses of both sexes.
Genital differentiation
A differentiation of the sex organSex organ
A sex organ, or primary sexual characteristic, as narrowly defined, is any of the anatomical parts of the body which are involved in sexual reproduction and constitute the reproductive system in a complex organism; flowers are the reproductive organs of flowering plants, cones are the reproductive...
can be seen. However, this is only the external genital differentiation. There is also an internal genital differentiation.
Internal genital differentiation
GonadGonad
The gonad is the organ that makes gametes. The gonads in males are the testes and the gonads in females are the ovaries. The product, gametes, are haploid germ cells. For example, spermatozoon and egg cells are gametes...
s are histologically distinguishable by 6–8 weeks of gestation. A fetus of that age has both mesonephric (wolffian) and paramesonephric (mullerian) ducts. Subsequent development of one set and degeneration of the other depends on the presence or absence of two testicular hormones: testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
and AMH. Disruption of typical development may result in the development of both, or neither, duct system, which may produce morphologically intersexual individuals.
Local testosterone causes each wolffian duct to develop into epididymis
Epididymis
The epididymis is part of the male reproductive system and is present in all male amniotes. It is a narrow, tightly-coiled tube connecting the efferent ducts from the rear of each testicle to its vas deferens. A similar, but probably non-homologous, structure is found in cartilaginous...
, vas deferens
Vas deferens
The vas deferens , also called ductus deferens, , is part of the male anatomy of many vertebrates; they transport sperm from the epididymis in anticipation of ejaculation....
, and seminal vesicles. Without male testosterone levels, wolffian ducts degenerate and disappear. Müllerian ducts develop into a uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
, fallopian tube
Fallopian tube
The Fallopian tubes, also known as oviducts, uterine tubes, and salpinges are two very fine tubes lined with ciliated epithelia, leading from the ovaries of female mammals into the uterus, via the utero-tubal junction...
s, and upper vagina
Vagina
The vagina is a fibromuscular tubular tract leading from the uterus to the exterior of the body in female placental mammals and marsupials, or to the cloaca in female birds, monotremes, and some reptiles. Female insects and other invertebrates also have a vagina, which is the terminal part of the...
unless AMH induces degeneration. The presence of a uterus is stronger evidence of absence of testes than the state of the external genitalia.
External genital differentiation
By 7 weeks, a fetus has a genital tubercleGenital tubercle
A phallic tubercle or genital tubercle is a body of tissue present in the development of the urinary and reproductive organs. It forms in the ventral, caudal region of mammalian embryos of both sexes, and eventually develops into a phallus...
, urogenital groove and sinus, and labioscrotal folds
Labioscrotal folds
The labioscrotal folds are paired structures in the human embryo that represent the final stage of development of the caudal end of the external genitals before sexual differentiation. In both males and females the two swellings merge:* In the female, they become the posterior labial commissure...
. In females, without excess androgens, these become the clitoris
Clitoris
The clitoris is a sexual organ that is present only in female mammals. In humans, the visible button-like portion is located near the anterior junction of the labia minora, above the opening of the urethra and vagina. Unlike the penis, which is homologous to the clitoris, the clitoris does not...
, urethra
Urethra
In anatomy, the urethra is a tube that connects the urinary bladder to the genitals for the removal of fluids out of the body. In males, the urethra travels through the penis, and carries semen as well as urine...
and vagina
Vagina
The vagina is a fibromuscular tubular tract leading from the uterus to the exterior of the body in female placental mammals and marsupials, or to the cloaca in female birds, monotremes, and some reptiles. Female insects and other invertebrates also have a vagina, which is the terminal part of the...
, and labia.
Males become externally distinct between 8 and 12 weeks, as androgens enlarge the phallus and cause the urogenital groove and sinus to fuse in the midline, producing an unambiguous penis
Penis
The penis is a biological feature of male animals including both vertebrates and invertebrates...
with a phallic urethra, and a thinned, rugated scrotum
Scrotum
In some male mammals the scrotum is a dual-chambered protuberance of skin and muscle containing the testicles and divided by a septum. It is an extension of the perineum, and is located between the penis and anus. In humans and some other mammals, the base of the scrotum becomes covered with curly...
.
A sufficient amount of any androgen can cause external masculinization
Virilization
In biology and medicine, virilization refers to the biological development of sex differences, changes that make a male body different from a female body. Most of the changes of virilization are produced by androgens...
. The most potent is dihydrotestosterone
Dihydrotestosterone
Dihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
(DHT), generated from testosterone in skin and genital tissue by the action of 5α-reductase. A male fetus may be incompletely masculinized if this enzyme is deficient
5-alpha-reductase deficiency
5-Alpha-reductase deficiency is an autosomal recessive intersex condition caused by a mutation of the 5-alpha reductase type 2 gene.-Normal function:...
. In some disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
s and circumstances, other androgens may be present in high enough concentrations to cause partial or (rarely) complete masculinization of the external genitalia of a genetically female fetus.
Further sex differentiation of the external genitalia occurs at puberty
Puberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
, when androgen levels again become disparate. Male levels of testosterone directly induce growth of the penis, and indirectly (via DHT) the prostate
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....
.
Breast differentiation
Visible differentiation occurs at pubertyPuberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
, when estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
and other hormones cause breast
Breast
The breast is the upper ventral region of the torso of a primate, in left and right sides, which in a female contains the mammary gland that secretes milk used to feed infants.Both men and women develop breasts from the same embryological tissues...
s to develop in girls. However, fetal or neonatal androgens may modulate later breast development by reducing the capacity of breast tissue to respond to later estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
.
Hair differentiation
The amount and distribution of body hairHair
Hair is a filamentous biomaterial, that grows from follicles found in the dermis. Found exclusively in mammals, hair is one of the defining characteristics of the mammalian class....
differs between the sexes. Males have more terminal hair
Terminal hair
Terminal hairs are thick, long, and dark, as compared with vellus hair. During puberty, the increase in androgenic hormone levels causes vellus hair to be replaced with terminal hair in certain parts of the human body...
, especially on the face
Facial hair
Facial hair is a secondary sex characteristic of human males. Men often start developing facial hair in the later years of puberty or adolescence, approximately between 17–20 years of age, and most do not finish developing a fully adult beard until their early 20s or even later...
, chest
Chest hair
The term chest hair is generally used to describe hair that grows on the chest of human males, in the region between the neck and the abdomen. Chest hair, which is a secondary sex characteristic, develops during and after puberty...
, abdomen
Abdominal hair
The term abdominal hair refers to the hair that grows on the abdomen of humans and non-human mammals, in the region between the pubic area and the thorax . The growth of abdominal hair follows the same pattern on nearly all mammals, vertically from the pubic area upwards and from the thorax...
and back, and females have more vellus hair, which is less visible. This may also be linked to neoteny
Neoteny
Neoteny , also called juvenilization , is one of the two ways by which paedomorphism can arise. Paedomorphism is the retention by adults of traits previously seen only in juveniles, and is a subject studied in the field of developmental biology. In neoteny, the physiological development of an...
in humans, as vellus hair is a juvenile characteristic.
Other body differentiation
The differentiation of other parts of the body than the sex organSex organ
A sex organ, or primary sexual characteristic, as narrowly defined, is any of the anatomical parts of the body which are involved in sexual reproduction and constitute the reproductive system in a complex organism; flowers are the reproductive organs of flowering plants, cones are the reproductive...
creates the secondary sex characteristic
Secondary sex characteristic
Secondary sex characteristics are features that distinguish the two sexes of a species, but that are not directly part of the reproductive system. They are believed to be the product of sexual selection for traits which give an individual an advantage over its rivals in courtship and aggressive...
s.
General habitus and shape of body and face, as well as sex hormone levels, are similar in prepubertal boys and girls. As puberty progresses and sex hormone levels rise, obvious differences appear.
In males, testosterone directly increases size and mass of muscles, vocal cords, and bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
s, enhancing strength, deepening the voice, and changing the shape of the face and skeleton. Converted into DHT in the skin, it accelerates growth of androgen-responsive facial and body hair. Taller stature is largely a result of later puberty and slower epiphyseal fusion.
In females, in addition to breast differentiation, estrogen also widens the pelvis
Pelvis
In human anatomy, the pelvis is the lower part of the trunk, between the abdomen and the lower limbs .The pelvis includes several structures:...
and increases the amount of body fat
Fat
Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...
in hips, thighs, buttocks, and breasts. Estrogen also induces growth of the uterus, proliferation of the endometrium
Endometrium
-Function:The endometrium is the innermost glandular layer and functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a...
, and menses
Menstrual cycle
The menstrual cycle is the scientific term for the physiological changes that can occur in fertile women for the purpose of sexual reproduction. This article focuses on the human menstrual cycle....
.
The difference in adult masculine and feminine faces is largely a result of a more prominent chin, heavier jaw and jaw muscle development and thicker orbital eyebrow bossing. Masculine features on average are slightly thicker and coarser. Androgen-induced recession of the male hairline accentuates these differences by middle adult life.
Sexual dimorphism of skeletal structure develops during childhood, and becomes more pronounced at adolescence. Sexual orientation has been demonstrated to correlate with skeletal characters that become dimorphic during early childhood (such as arm length to stature ratio) but not with characters that become dimorphic during puberty (such as shoulder width) (Martin & Nguyen, 2004).
Brain differentiation
In most animals, differences of exposure of a fetal or infant brainBrain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
to sex hormones produce significant differences of brain structure and function which correlate with adult reproductive behavior.
This seems to be the case in humans as well; sex hormone levels in male and female fetuses and infants differ, and both androgen receptors and estrogen receptors have been identified in brains. Several sex-specific genes not dependent on sex steroids are expressed differently in male and female human brains. Structural sex differences begin to be recognizable by 2 years of age, and in adult men and women include size and shape of corpus callosum
Corpus callosum
The corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication...
and certain hypothalamic
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
nuclei, and the gonadotropin
Gonadotropin
Gonadotropins are protein hormones secreted by gonadotrope cells of the pituitary gland of vertebrates. This is a family of proteins, which include the mammalian hormones follitropin , lutropin , placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin , as well as at least two...
feedback response to estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
.
Psychological and behavioral differentiation
Human adults and children show many psychological and behavioral sex differences, both dichotomous and dimorphic. Some (e.g., dress) are learned and obviously cultural. Others are demonstrable across cultures and may have both biological and learned determinants. For example, girls are, on average, more verbally fluent than boys, but males, on average, are better at spatial calculation. Because we cannot explore hormonal influences on human behavior experimentally, and because potential political implications are so unwelcome to many factions of society, the relative contributionsNature versus nurture
The nature versus nurture debate concerns the relative importance of an individual's innate qualities versus personal experiences The nature versus nurture debate concerns the relative importance of an individual's innate qualities ("nature," i.e. nativism, or innatism) versus personal experiences...
of biological factors and learning to human psychological and behavioral sex differences (especially gender identity, role, and orientation
Sexual orientation
Sexual orientation describes a pattern of emotional, romantic, or sexual attractions to the opposite sex, the same sex, both, or neither, and the genders that accompany them. By the convention of organized researchers, these attractions are subsumed under heterosexuality, homosexuality,...
) remain unsettled and controversial.
Current theories of mechanisms of sexual differentiation of brain and behaviors in humans are based primarily on three sources of evidence: animal research involving manipulation of hormones in early life, observation of outcomes of small numbers of individuals with disorders of sexual development (intersex
Intersex
Intersex, in humans and other animals, is the presence of intermediate or atypical combinations of physical features that usually distinguish female from male...
conditions or cases of early sex reassignment
Sex reassignment
Sex reassignment may refer to:* Sex reassignment, changing the sex assignment of an infant or child by parents and doctors, usually because of fuller understanding of an intersex condition....
), and statistical distribution of traits in populations (e.g., rates of homosexuality in twins). Many of these cases suggest some genetic or hormonal effect on sex differentiation of behavior and mental traits; others do not.
In addition to affecting development, changing hormone levels affect certain behaviors or traits that are gender dimorphic, such as superior verbal fluency among women.
In most mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian species females are more oriented toward child rearing and males toward competition with other males.
Biology of gender
Biology of gender is the scientific analysis of the physical basis for behavioural differences between men and women. It deals with gender identityGender identity
A gender identity is the way in which an individual self-identifies with a gender category, for example, as being either a man or a woman, or in some cases being neither, which can be distinct from biological sex. Basic gender identity is usually formed by age three and is extremely difficult to...
, gender roles and sexual orientation
Sexual orientation
Sexual orientation describes a pattern of emotional, romantic, or sexual attractions to the opposite sex, the same sex, both, or neither, and the genders that accompany them. By the convention of organized researchers, these attractions are subsumed under heterosexuality, homosexuality,...
.
Defeminization and masculinization
DefeminizationDefeminization
Defeminization is a term in developmental biology, especially zoology, referring to an aspect of the process of sexual differentiation by which a potential female-specific structure, function, or behavior is prevented from developing by one of the processes of male development...
and masculinization are the differentiating processes that a fetus goes through to become male. From this perspective, the female is the default path for a developing human being in that gene actions that are eliminated and that are necessary for formation of male genitalia lead to the development of external female genitalia.
Biologically, this perspective is supported by the fact that there are neither female genes nor female hormones that correspond to the hormones active in males only. Estrogen, for instance, is present in both the male and female fetus.
See also
- Sex determination and differentiation (human)Sex determination and differentiation (human)Human sex refers to the processes by which an individual becomes either a male or female during development.-The Jost Paradigm:Under typical circumstances, the sex of an individual will be determined and expressed through the following mechanisms:...
- VirilizationVirilizationIn biology and medicine, virilization refers to the biological development of sex differences, changes that make a male body different from a female body. Most of the changes of virilization are produced by androgens...
- Sexual dimorphismSexual dimorphismSexual dimorphism is a phenotypic difference between males and females of the same species. Examples of such differences include differences in morphology, ornamentation, and behavior.-Examples:-Ornamentation / coloration:...
- Sex differences in humansSex differences in humansA sex difference is a distinction of biological and/or physiological characteristics associated with either males or females of a species. These can be of several types, including direct and indirect. Direct being the direct result of differences prescribed by the Y-chromosome, and indirect being...
- List of homologues of the human reproductive system
- genderGenderGender is a range of characteristics used to distinguish between males and females, particularly in the cases of men and women and the masculine and feminine attributes assigned to them. Depending on the context, the discriminating characteristics vary from sex to social role to gender identity...
- Sex-determination systemSex-determination systemA sex-determination system is a biological system that determines the development of sexual characteristics in an organism. Most sexual organisms have two sexes. In many cases, sex determination is genetic: males and females have different alleles or even different genes that specify their sexual...
- XY sex-determination systemXY sex-determination systemThe XY sex-determination system is the sex-determination system found in humans, most other mammals, some insects and some plants . In this system, females have two of the same kind of sex chromosome , and are called the homogametic sex. Males have two distinct sex chromosomes , and are called...
- X0 sex-determination systemX0 sex-determination systemThe X0 sex-determination system is a system that hymenopterans, grasshoppers, crickets, cockroaches, and some other insects use to determine the sex of their offspring. In this system, there is only one sex chromosome, referred to as X. Males only have one X chromosome , while females have two...
- ZW sex-determination systemZW sex-determination systemThe ZW sex-determination system is a system that determines the sex of offspring in birds, some fish and crustaceans such as the giant river prawn, some insects , and some reptiles, including Komodo dragons...
- Haplo-diploid sex-determination systemHaplo-diploid sex-determination systemThe haplodiploid sex-determination system determines the sex of the offspring of many hymenopterans , spider mites, coleopterans and rotifers. In this system, sex is determined by the number of sets of chromosomes an individual receives...
- XY sex-determination system
- Fetal genital developmentFetal genital developmentFetal genital development refers to the sequence of events which leads to the development of the genitals and their adnexa.-Sequence:A few weeks after fertilization, the initial appearance of the human fetal genitalia is basically feminine: a pair of "urogenital folds" with a small protuberance in...
External links
- Human Sexual Differentiation by P. C. Sizonenko
- The Ciba Collection of Medical Illustrations: Vol.2, Reproductive System by Frank H. Netter, M.D. comparing female and male reproductive systems development and anatomy
- Development of the Female Sexual & Reproductive Organs – illustrations comparing female and male genitalia during the early development