Scientists at UC Berkeley uncovered evidence that female fertility is regulated by chronic stress, even after the stress has ended. More interestingly, investigators found that they could return female fertility to normal through genetic silencing of a brain derived inhibitory peptide.

“What’s absolutely amazing is that one single gene controls this complex reproductive system, and that you can elegantly knock this gene down and change the reproductive outcome completely,” says Daniela Kaufer, Ph.D., associate professor of integrative biology and head of the research team that preformed these studies.

In their study (“Knockdown of hypothalamic RFRP3 prevents chronic stress-induced infertility and embryo resorption”) published in eLife, the research team found that chronic stress in female rats triggered increased levels of RFamide-related peptide-3 (RFRP3), the mammalian analog of gonadotropin inhibitory hormone (GnIH). Using a technique called RNA inhibition, Dr. Kaufer and her team were able to silence the RFRP3 and show that it is key to the stress-fertility link. While previous studies in male rats saw similar effects on fertility, this current work found that chronic stress had a longer and more profound effect on female reproductive health. 

“GnIH seems to be the main player, because it is elevated in the brain’s hypothalamus for a full estrus cycle after the stress ends,” Dr. Kaufer said. “When we knocked down levels of GnIH, we restored all reproductive behavior back to normal.”

George Bentley, Ph.D., associate professor of integrative biology at UC Berkeley and coauthor on the current study, believes there is widespread application of the current data that goes beyond human infertility treatment. He is excited about the prospect of manipulating GnIH levels to improve breeding success among captive animals.

“A lot of wild birds and vertebrates won’t breed in captivity in part, we think, because of chronic low-level stress, just a chronic slight elevation in glucocorticoid stress hormones might influence the GnIH system and inhibit reproduction sufficiently to stop females from ovulating properly,” says Dr. Bentley, noting that this research provides a greater appreciation of stress on reproductive biology, whether for endangered captive animals or couples struggling with fertility issues.








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