Modifying gene may be solution to female infertility, study finds

Stress has been known to prevent fertility and cause miscarriages, but scientists have now shown that knocking down a single gene may be able to offset these effects.

Researchers at the University of California, Berkeley conducted the study on rats. According to a news release, the study authors are the first to analyze the link among the molecular bases of fertility, sex drive and stress.

The researchers say that because the gene in question encodes for a hormone common in mammals, the findings may apply to humans.

"Remarkably, genetic silencing of a single chemical compound, a peptide called RFRP3, restores mating and pregnancy success to a rate indistinguishable from non-stress controls," study author Daniela Kaufer, an integrative biology professor at UC, Berkeley, said in the news release.

Gene knockdown involves the modification of DNA that typically removes all or part of a gene, according to the National Institutes of Health (NIH).

Study authors also found that pre-conception stress had long-term effects on female reproductive fitness and pregnancy. Stressed females were not only less motivated to mate, but they also became pregnant less often, and those that did copulate saw fewer live pups make it to term. But all of these impacts were eliminated by silencing RFRP3, according to the news release.

Researchers defined reproductive success by the percentage of female rats that brought a litter to full term. Reproductive success dropped from 80 percent to 20 percent when females were exposed to preconception stress. Success was restored to 80 percent when RFRP3 was knocked down. Embryo survival rates also jumped back to 94 percent when RFPR3 was exterminated.

RFRP3 is made in the hypothalamus of the brain, which helps control the pituitary gland in response to stress, according to the NIH.

In females, RFRP3 decreases the normal surge in hormones that accompanies ovulation, and it may be directly regulated by the stress hormone corticosterone. Researchers observed that RFRP3 continued to impact the rats’ reproductive function even after recovery from stress, when corticosterone levels had returned to normal.

The Centers for Disease Control and Prevention (CDC) estimates that 6.7 million, or about 11 percent of, women ages 15 to 44 in the United States struggle with impaired fecundity,  the inability to get pregnant or carry a baby to term.

Six percent of married women ages 15 to 44 in the U.S. are infertile, according to the CDC.

"A strikingly high proportion of healthy women struggle with fertility,” UC Berkeley graduate student and lead author Anna Geraghty said in the news release. “Our findings provide a new focus for the clinical study of human reproductive health.”

The study was published Tuesday in the journal eLife.