Reproductive immunology
Encyclopedia
Reproductive immunology refers to a field of medicine that studies interactions (or the absence of them) between the immune system
and components related to the reproductive system
, such as maternal immune tolerance towards the fetus, or immunological interactions across the blood-testis barrier
. The concept has been used by fertility clinic
s to explain the fertility problems
, recurrent miscarriage
s and pregnancy complications
observed when this state of immunological tolerance is not successfully achieved. Immunological therapy is the new up and coming method for treating many cases of previously "unexplained infertility
" or recurrent miscarriage.
, it is not normally rejected, suggests that the immunological system of the mother plays an important role in pregnancy. The placenta also plays an important part in protecting the embryo for the immune attack from the mother's system. Studies also propose that proteins in semen may help woman’s immune system prepare for conception and pregnancy. For example, there is substantial evidence for exposure to partner's semen as prevention for pre-eclampsia, largely due to the absorption of several immune modulating factors present in seminal fluid, such as transforming growth factor beta (TGFβ).
has been described as three immunoglobulin isotopes (IgG, IgA, IgM) each of which targets different part of the spermatozoa. If more than 10% of the sperm are bound to anti-sperm antibodies (ASA), then infertility is suspected. The blood-testis barrier
separates the immune system and the developing spermatozoa. The tight junction
between the Sertoli cell
s form the blood-testis barrier but it is usually breached by physiological leakage. Not all sperms are protected by the barrier because spermatogonia and early spermatocytes are located below the junction. They are protected by other means like immunologic tolerance and immunomodulation
.
Infertility after anti-sperm antibody binding can be caused by autoagglutination
, sperm cytotoxicity
, blockage of sperm-ovum interaction, and inadequate motility. Each presents itself depending on the binding site
of ASA.
. This vaccine is currently being tested in animals and hopefully will be an effective contraceptive for humans. Normally, spermatozoa fuse with the zona pellucida surrounding the mature oocyte; the resulting acrosome reaction
breaks down the egg's tough coating so that the sperm can fertilize the oovum. The mechanism of the vaccine is injection with cloned ZP cDNA, therefore this vaccine is a DNA based vaccine. This results in the production of antibodies against the ZP, which stop the sperm from binding to the zona pellucida and ultimately from fertilizing the oovum.
Another vaccine in investigation is one against HCG. This immunization would produce antibodies against hCG and TT. Antibodies against hCG would prevent the maintenance of the uterus for a viable pregnancy therefore preventing contraception.
Another vaccine that is utilized is the peptide ß hCG is more specific to hCG and a more rapid and effective response occurs in the absence of LH, FSH, and TSH.
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
and components related to the reproductive system
Reproductive system
The reproductive system or genital system is a system of organs within an organism which work together for the purpose of reproduction. Many non-living substances such as fluids, hormones, and pheromones are also important accessories to the reproductive system. Unlike most organ systems, the sexes...
, such as maternal immune tolerance towards the fetus, or immunological interactions across the blood-testis barrier
Blood-testis barrier
The blood–testis barrier is a physical barrier between the blood vessels and the seminiferous tubules of the animal testes...
. The concept has been used by fertility clinic
Fertility clinic
Fertility clinics are staffed medical clinics that assist couples, and sometimes individuals, who want to become parents but for medical reasons have been unable to achieve this goal via the natural course...
s to explain the fertility problems
Infertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
, recurrent miscarriage
Miscarriage
Miscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation...
s and pregnancy complications
Complications of pregnancy
Complications of pregnancy are the symptoms and problems that are associated with pregnancy. There are both routine problems and serious, even potentially fatal problems. The routine problems are normal complications, and pose no significant danger to either the woman or the fetus...
observed when this state of immunological tolerance is not successfully achieved. Immunological therapy is the new up and coming method for treating many cases of previously "unexplained infertility
Unexplained infertility
Unexplained infertility is infertility that is idiopathic in the sense that its cause remains unknown even after an infertility work-up, usually including semen analysis in the man and assessment of ovulation and fallopian tubes in the woman.-Possible causes:...
" or recurrent miscarriage.
Between mother and fetus
The fact that the embryo's tissue is half foreign and unlike mismatched organ transplantOrgan transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
, it is not normally rejected, suggests that the immunological system of the mother plays an important role in pregnancy. The placenta also plays an important part in protecting the embryo for the immune attack from the mother's system. Studies also propose that proteins in semen may help woman’s immune system prepare for conception and pregnancy. For example, there is substantial evidence for exposure to partner's semen as prevention for pre-eclampsia, largely due to the absorption of several immune modulating factors present in seminal fluid, such as transforming growth factor beta (TGFβ).
Sperm cells within a male
The presence of anti-sperm antibodies in infertile men was first reported in 1954 by Rumke and Wilson. It has been noticed that the number of cases of sperm autoimmunity is higher in the infertile population leading to the idea that autoimmunity could be a cause of infertility. anti sperm antigenSPAG6
Sperm-associated antigen 6 is a protein that in humans is encoded by the SPAG6 gene.-Further reading:...
has been described as three immunoglobulin isotopes (IgG, IgA, IgM) each of which targets different part of the spermatozoa. If more than 10% of the sperm are bound to anti-sperm antibodies (ASA), then infertility is suspected. The blood-testis barrier
Blood-testis barrier
The blood–testis barrier is a physical barrier between the blood vessels and the seminiferous tubules of the animal testes...
separates the immune system and the developing spermatozoa. The tight junction
Tight junction
Tight junctions, or zonula occludens, are the closely associated areas of two cells whose membranes join together forming a virtually impermeable barrier to fluid. It is a type of junctional complex present only in vertebrates...
between the 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 form the blood-testis barrier but it is usually breached by physiological leakage. Not all sperms are protected by the barrier because spermatogonia and early spermatocytes are located below the junction. They are protected by other means like immunologic tolerance and immunomodulation
Immunomodulator
An immunomodulator, also known as an immunotherapy is a substance which has an effect on the immune system.- Immunosuppressants :Inhibits immune response in organ transplantation and autoimmune diseases.- Immunostimulants :...
.
Infertility after anti-sperm antibody binding can be caused by autoagglutination
Autoagglutination
Autoagglutination represents clumping of an individual's red blood cells by his or her own serum due to the RBCs being coated on their surface by antibodies....
, sperm cytotoxicity
Cytotoxicity
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are a chemical substance, an immune cell or some types of venom .-Cell physiology:...
, blockage of sperm-ovum interaction, and inadequate motility. Each presents itself depending on the binding site
Binding site
In biochemistry, a binding site is a region on a protein, DNA, or RNA to which specific other molecules and ions—in this context collectively called ligands—form a chemical bond...
of ASA.
Immunocontraceptive vaccine
Experiments are undergoing to test the effectiveness of an immunocontraceptive vaccine that inhibits the fusing of spermatozoa to the zona pellucidaZona pellucida
The zona pellucida is a glycoprotein membrane surrounding the plasma membrane of an oocyte. It is a vital constitutive part of the latter, external but of essential importance to it...
. This vaccine is currently being tested in animals and hopefully will be an effective contraceptive for humans. Normally, spermatozoa fuse with the zona pellucida surrounding the mature oocyte; the resulting acrosome reaction
Acrosome reaction
During fertilization, a sperm must first fuse with the plasma membrane and then penetrate the female egg in order to fertilize it. Fusing to the egg usually causes little problem, whereas penetrating through the egg's hard shell can present more of a problem to the sperm...
breaks down the egg's tough coating so that the sperm can fertilize the oovum. The mechanism of the vaccine is injection with cloned ZP cDNA, therefore this vaccine is a DNA based vaccine. This results in the production of antibodies against the ZP, which stop the sperm from binding to the zona pellucida and ultimately from fertilizing the oovum.
Another vaccine in investigation is one against HCG. This immunization would produce antibodies against hCG and TT. Antibodies against hCG would prevent the maintenance of the uterus for a viable pregnancy therefore preventing contraception.
Another vaccine that is utilized is the peptide ß hCG is more specific to hCG and a more rapid and effective response occurs in the absence of LH, FSH, and TSH.