Affect the offspring? Nature Supplement: This female infertility is far more complicated than we think
May 18, 2018 Source: Biological Exploration of: Flora
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];Polycystic ovary syndrome (PCOS) affects more than 10% of women of childbearing age worldwide, is the main cause of female infertility, easily increases the risk of metabolic diseases, and has a genetic predisposition. Now, an article published in the journal Nature Medicine reveals that the occurrence of PCOS is related to the developmental environment of the fetus in the womb.
Polycystic ovary syndrome has many typical symptoms, including anovulation (or sparse ovulation), polycystic ovary, and androgen. But its cause of illness has always been an unsolved mystery.
Many studies have shown that when pregnant women show polycystic ovary syndrome, the fetus (female) in the uterus will also undergo hormone changes, and may show symptoms of PCOS after many years. In particular, several studies based on pregnant animals have found that exposure to high levels of androgens (similar to PCOS) during pregnancy can cause progeny to appear as PCOS-like symptoms such as anovulation.
Now, the neuroendocrinologist Paolo Giacobini of the University of Lille in France has led the team to find the key evidence behind this: an hormone antimüllerian (AMH), which is secreted by the ovaries, interacts with a group of neurons in the mother's brain and triggers the level. The association reaction, which in turn destroys the enzymes of the placenta, ultimately leads to progeny showing symptoms similar to PCOS.
Doi:10.1038/s41591-018-0035-5
1 , excessive ovarian hormone
Antimüllerian hormone is secreted by small follicles in the ovaries. Because of the abnormal increase in follicles in women with polycystic ovary syndrome, more AMH hormones are secreted.
In a previous study, the Paolo Giacobini team found that AMH hormones affect a group of neurons in the brain, which stimulates the pituitary gland to secrete luteinizing hormone (LH). For healthy women, the secretion of LH promotes ovulation. However, PCOS patients will be inhibited by ovulation due to high levels of LH, and testosterone levels will rise.
The Paolo Giacobini team recruited four groups of women in the second trimester—normally healthy pregnant women and PCOS pregnant women, obese healthy pregnant women, and PCOS pregnant women, to collect their blood samples. Under normal circumstances, AMH hormone levels will decline due to pregnancy, because the ovary is not active during this period.
However, it was found that the AMH hormone levels of pregnant women with normal weight were 2-3 times higher than those of the other three groups. (Why is obesity PCOS pregnant women with normal AMH hormone levels? This is still a mystery.)
2 , mouse test: androgen affects the fetus
How does the upregulated androgen cause the genetic predisposition of PCOS? To find out, the Paolo Giacobini team used pregnant mice as a model to give them AMH hormones during the second trimester to simulate the characteristics of women with PCOS. It was found that female offspring born in mice also showed symptoms similar to PCOS, such as sparse ovulation and high androgen.
The study found that under the stimulation of AMH hormones, excessive testosterone secreted by the mother will cross the placenta and affect the fetus. The researchers speculate that the reason for this phenomenon is that AMH hormones inhibit the level of aromatase (an enzyme in the placenta, which is responsible for converting testosterone to estrogen). Once the aromatase activity is reduced, excess testosterone affects the fetus in an environment similar to PCOS.
3 , testosterone is the key to PCOS
This latest study was done in a mouse model. Does human existence have the same mechanism? Jeffrey Chang, a reproductive endocrinologist at the University of California, believes that this is still unknown because human placenta expresses far more aromatic enzymes than mouse placenta, so AMH hormones may be difficult to inhibit aromatase.
However, it is worth noting that this new study shows that testosterone is the key to the risk of fetus burying PCOS, once again corroborating the previous findings that testosterone (a part of the AMH cascade) may be the culprit of PCOS. ".
References: 1) Scientists may be closer to understanding a mysterious but common cause of female infertility
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