We spoke to two researchers from karolinskainst about their latest work that investigated how PCOS can affect the health of future generations of men. Read the full interview here:
Interview conducted by Danielle Ellis, B.Sc.May 29 2023 Thought LeadersElisabet Stener-Victorin/Qiaolin DengProfessor/Assistant Professor Karolinska Institutet
In polycystic ovary syndrome the ovaries produce too much of the sex hormone testosterone. What is the global incidence of this disease, and how does it impact the lives of affected women? PCOS affects approximately 15% of women of reproductive age worldwide. It is diagnosed when two of three criteria are met: polycystic ovarian morphology, oligo/anovulation, and clinical or biochemical hyperandrogenism.
Recently, we demonstrated that PCOS-like traits, induced by exposing pregnant mice to dihydrotestosterone , are passed on from mothers to daughters , granddaughters , and even to great-granddaughters . Moreover, this transmission was accompanied by transcriptional and mitochondrial perturbations of oocytes. Importantly, several of the transcriptomic signatures were also detectable in blood from daughters of women with PCOS, supporting a role for epigenetic inheritance of the syndrome in humans.
We used our previously validated mouse models to investigate whether first-generation male offspring that were directly exposed to diet-induced maternal obesity, prenatal androgens , or the combination of the two exposures could develop reproductive and metabolic traits in adult males and if such traits are passed on to F2 and F3 male offspring.
Given the effect that the mother's diet during pregnancy had on the fat distribution and metabolism of male offspring, do you hypothesize that there is an epigenetic cause? Yes, as we used pure genetic background wild-type mice to exclude the effects of genetic cause. Our experimental design combining a diet-induced obesity mouse model with a prenatal androgen exposure mouse model allows us to study epigenetic causes.
What is next for you and your research? We hope to identify biomarkers, allowing early detection of boys at risk, enabling prevention, and opening new horizons for treatment strategies rather than managing symptoms, thereby reducing the burden of disease in both women and men.
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