Removal Of 'Stress' Gene Shows Promise For Preventing Female Infertility And Miscarriages

There's nothing more worrying for a future parent than the prospect of miscarriage.

But now, new research suggests that by knocking down a single gene, stress-induced miscarriages and infertility in females could be prevented.

The study, conducted by scientists at University of California Berkeley, offers an insight into the molecular links between decreased sex drive, delayed pregnancy and an increase in miscarriages.

The research, published in open access journal eLife, was carried out in rats. The gene encodes for a hormone that is common across all mammals could apply to humans and to endangered animals whose survival depends on captive breeding.

“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,” says Professor Daniela Kaufer, associate professor of integrative biology and co-author of the study.

The team also carried out the first investigation into the long-term impact of pre-conception stress on female reproductive fitness and pregnancy. They found marked and persistent reproductive dysfunction even after recovery from stress.

A miscarriage is the loss of a pregnancy during the first 23 weeks. The main sign of a miscarriage is vaginal bleeding, which may be followed by cramping and pain in the lower abdomen.

Among women who know they are pregnant, it is believed that one in seven of these pregnancies will end in miscarriage, according to NHS Choices. With many more miscarriages occurring before a woman is even aware that she is pregnant.

“Fertility problems are fairly common and around one in seven couples have trouble conceiving," says Dr Nitin Shori, Medical Director of the Pharmacy2U Online Doctor service. "There are many things that cause infertility, but in some cases it can be linked to stress."

“In terms of miscarriage, it's a common misconception that this is closely connected to a woman’s stress levels," he adds. "Miscarriage can be attributed to various things, including problems with the developing foetus, womb abnormalities and placenta issues.”

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The study found that stressed female rats were less motivated to mate, became pregnant less often and - in those that did copulate successfully - fewer live pups made it to term and were instead reabsorbed into the uterus.

The findings show that the impact of stress lingers long after the stress has been removed. These marked effects were completely eliminated by knocking down RFRP3.

"One of the most surprising aspects of our findings was the persistent effect of stress on embryo survival and the role RFRP3 may play in that," says Anna Geraghty, lead-author of the study and a graduate student at Berkeley.

"Though the stress ended four days prior to mating, stressed animals exhibited higher rates of embryo resorption, indicating that the effects of the chronic stress lasted at least two weeks past the cessation of the stressor.

“A strikingly high proportion of healthy women struggle with fertility and our findings provide a new focus for the clinical study of human reproductive health,” she adds.

While it seems like a promising study, there's still a long way to go in terms of conducting the research on humans.

George Bentley, associate professor of integrative biology says that it would depend on a large number of variables: "The number of people working on the problem, the identification of the full suite of actions of RFRP3 in humans and ways in which it is modulated by other hormones.

"We still do not understand the full extent of RFRP3’s actions in humans, I think we still have a way to go before considering such a therapy," he adds.