Knocking down single gene can fix stress-induced infertility

A team of scientists has discovered that by knocking down a single gene, they can fix stress-induced infertility in rats.

Although stress has been linked to decreased sex drive, delayed pregnancy and an increase in miscarriages, this is the first time the molecular basis for the links has been explored.

Daniela Kaufer from the University of California Berkeley said that 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.

Stressed females 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.

Lead author Anna Geraghty said that 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.

RFRP3 is the mammalian equivalent of a hormone first identified in Japanese quail and is made in the hypothalamus portion of the brain. One way it exerts its effect on females is by decreasing the normal surge in hormones that accompanies ovulation.

It may be directly regulated by the stress hormone corticosterone. However, even after recovery from stress, when corticosterone levels have returned to normal, RFRP3 was found to continue exerting its effect on reproduction.

The study is published in the open access journal eLife.