A study recently published in Nature Medicine uncovers a possible cause of female infertility caused by polycystic ovary syndrome.
Up to 10-18% of women of reproductive age worldwide are affected by polycystic ovary syndrome (PCOS). Women with this hormonal disorder have enlarged ovaries covered with small follicles, which contain eggs that have not matured properly. Along with symptoms of excessive hair growth, acne, and irregular menstruation, PCOS is also a major cause of female infertility. This condition has a strong genetic link, meaning that it can be passed from mother to daughter. However, as this accounts for approximately 50% of cases only, scientists believe that other factors may contribute to this condition.
AMH levels are higher in women with polycystic ovary syndrome
Women with PCOS have more follicles than usual; therefore, they tend to have two to three-fold higher levels of anti-Müllerian hormone (AMH), a hormone produced by follicles on the ovary. AMH levels usually decrease during pregnancy in women with no fertility issues because the ovaries are not active. Scientists have always assumed that the same was true for women with PCOS.
Recently, however, a French team found that AMH levels were actually much higher in pregnant women with PCOS compared to women with no female infertility problems. Although age did not affect AMH levels, lean women with PCOS tended to have higher AMH levels compared to lean controls. In addition, AMH levels were higher in lean women with increased levels of androgens, or male sex hormones, such as testosterone. Surprisingly, obese women with PCOS had similar levels of AMH and androgens to obese controls, although the reason for this was not clear. They published their results in Nature Medicine.
Fetal exposure to AMH can induce PCOS in female offspring
The team looked at the effects of elevated AMH levels on the fetus by injecting pregnant mice with AMH. AMH caused reproductive symptoms consistent with PCOS in female offspring including irregular ovulation and fertility issues. What’s more, the offspring also had neuroendocrine symptoms typical of PCOS including high levels of testosterone and luteinising hormone. The regions of the brain that regulate reproduction were also masculinized.
AMH triggers a cascade of events starting in the mother’s brain
These symptoms were traced back to the hormone responsible for releasing the luteinising hormone: the gonadotropin-releasing hormone, which is located in the pituitary gland in the brain. As the gonadotropin-releasing hormone can also be activated by AMH, the team speculated that elevated levels of AMH hyperactivate the gonadotropin-releasing hormone so that it constantly releases luteinising hormone. In women with PCOS, consistently high levels of luteinising hormone prevent ovulation and increase testosterone production.
AMH-induced symptoms of PCOS can be reversed
The team then looked at whether they could reverse these symptoms. To do this, they needed to find a substance, or an antagonist, that could prevent AMH from binding to the gonadotropin-releasing hormone. Treating the offspring with this antagonist reversed all of the AMH-induced infertility issues and normalized the neuroendocrine issues seen in the offspring.
Hope for female infertility
Although gonadotropin-releasing hormone antagonists have a history of safe use, using these to treat female infertility is still a long way off. Although the gonadotropin-releasing hormone antagonist used in this study showed promising results, it is important to be mindful that this study was undertaken in mice. It is therefore unclear whether the same results would be seen in humans. In addition, due to the potential risks associated with altering hormone levels during pregnancy, the team plans to continue investigating other treatment strategies.
Written by Natasha Tetlow, PhD
References
- Couzin-Frankel J. Scientists may be closer to understanding a mysterious but common cause of female infertility. Retrieved from http://www.sciencemag.org/news/2018/05/scientists-may-be-closer-understanding-mysterious-common-cause-female-infertility, accessed 27 August 2018.
- PCOS. Retrieved from https://jeanhailes.org.au/health-a-z/pcos/symptoms-causes, accessed 27 August 2018.
- Tata B et al. Elevated prenatal anti-Mullerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood. Nature Medicine. 2018; 24:834-846.
