Research has shown that a deficiency in the autoimmune regulator AIRE leads to problems with fertility and mating, affects testosterone levels and the development of hypogonadism.
The impossibility of conceiving a child is faced by up to 25 percent of couples of reproductive age in the world. Moreover, historically, problems with fertility - the ability to produce viable offspring - are explained by female pathologies, but about half of all such cases are associated with male factors. Although usually impaired reproductive function in the "stronger sex" correlates with external influences, the causes can be genetic and endocrine, and also occur as a result of stopping spermatogenesis, cryptorchidism (undescended testicle into the scrotum or located outside of it or improper descent), varicocele (varicose veins), sperm blockage, or genital infections.
About ten percent of the known causes of infertility in men are associated with immune conditions, including orchitis and epididymitis. Also, infection or damage to the male reproductive tract can lead to immune targeting of antigens that are unique to germ cells, seminal epithelium, epididymis, and / or vas deferens.
Monogenic autoimmune diseases that develop when one gene is deficient are less common. Among them - type 1 autoimmune polyendocrine syndrome (APS-1): it occurs as a result of mutations that disrupt the function in the autoimmune regulator gene (AIRE), is characterized by fungal infections of the skin and mucous membranes, hypoparathyroidism and primary chronic adrenal insufficiency, as well as high titers of autoantibodies in blood serum. In addition, APS-1 targets the reproductive organs, which often leaves patients infertile.
AIRE is a nuclear glycoprotein most prominently expressed in medullary epithelial cells of the thymus and plays a vital role in central immune tolerance due to its ability to induce indiscriminate expression of multiple antigens that are otherwise restricted to one or more other tissues.
Scientists from Michigan State University (USA) decided to identify immune targets that contribute to infertility in AIRE deficiency. For this, sick mice, as well as wild-type rodents, were mated with healthy females.
“AIRE-deficient males experienced dramatic reductions in mating frequency and fertility, hypogonadism (testicular failure) and a drop in serum testosterone levels. Approximately 15 percent of these mice had lymphocytic infiltration into the testes, accompanied by atrophy, azoospermia, and a decrease in the number of mitotically active germ cells. The rest of the test subjects showed normal testicular morphology, sperm count and motility. The spermatozoa of all glycoprotein-deficient mice were found to be defective in their ability to fertilize female oocytes in vitro. Lymphocytic infiltration into the epididymis, seminal bladder, and prostate was evident. Finally, AIRE expression was evident in the seminal epithelium, depending on age, as well as in the prostate gland. Our evidence suggests that AIRE-dependent central tolerance plays a critical role in maintaining male fertility,”says a study published in The American Journal of Pathology.
According to the authors of the study, the link between impaired central immune tolerance and fertility not only has potential consequences for men with APS-1, but can provide important information both about male autoimmune diseases in general and about unexplained cases of infertility. “By understanding the causes of infertility in men, it is possible to develop treatment and prevention methods to curb the degenerative processes that affect fertility,” the scientists noted.