Solution for stress-induced infertility

Stress is thought to be a major contributor to today’s high levels of infertility.

Our bodies are equipped to prevent conception during times of scarcity and social disruption. The body creates an environment which not suitable for conception. Chronic stress decreases sex drive in men and women, her ability to get pregnant and carry a foetus to term. It reduces fertility long after the stress has ended.

A recent study led by scientists of University of California, demonstrates that chronic stress activates gonadotropin inhibitory hormone (GnIH).  Thus by blocking GnIH negative reproductive consequences could be avoided. Moreover only a single gene controls this complex reproductive system, thus knocking out this gene would help to change the reproductive outcome.

GnIH, discovered only 15 years ago, in quail, was found to be a powerful suppressor of fertility. Its mammalian equivalent, RFRP (RFamide-related peptide), was isolated from humans. The production of RFRP was observed to be increased in brains of stress exposed male rats. The new study documented similar effects on fertility of female rats. However elevated levels of RFRP, induced by chronic stress lasted much longer in females than in male rats.

The whole set of experiments were conducted in rats. To test the effects of chronic stress, the female rats were confined for three hours a day for 18 days, and then allowed to relax for four days, the rat’s typical estrus period, akin to women’s 28-day menstrual period. It was also observed that by the end of stress-free break, cortisol(marker of stress) levels  returned to normal, though levels of the inhibitory hormone, RFRP3 still remained elevated. A decrease in reproductive behaviour was noticed even after the chronic stress was gone: from 80% pregnancy rate in normal rats to 20% in those who should have recovered from stress. The 20% that actually got pregnant also experienced an increased incidence of embryo resorption, equivalent of a miscarriage.

The researchers then used a virus to insert an RNA blocker of RFRP3 gene into the brain of stress exposed female rats. The RNA blocker knocked down the peptide hormone by about 75%. They turned the gene on after the stress ended, as they were not sure about the role of RFRP3 in pregnancy. However inhibition of RFRP3 during chronic stress restored all subsequent reproductive behaviour to normal: Mating behaviour, pregnancy rate and the amount of embryo resorption.

Human GnIH is expressed in brain and gonads and it inhibits the production of steroids in human ovaries. Thus it has the potential to be manipulated to address human infertility.

The experts are confident about the potential of knocking down GnIH to improve breeding success in captive animals particularly those are threatened with extinction in the wild. In the other way round over expression of RFRP in the brain and gonads could cause infertility in pest species or untamed cats and dogs.

The study is published in the Jan. 13 issue of the journal eLife.

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Arunima Maiti

Arunima Maiti

Biomedical scientist with special interest in reproductive biology.

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