Transgenerational transmission of reproductive and metabolic dysfunction in the male progeny of polycystic ovary syndrome.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37148878.
- Also identified by DOI 10.1016/j.xcrm.2023.101035 and PMC identifier 10213875.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The transgenerational maternal effects of polycystic ovary syndrome (PCOS) in female progeny are being revealed. As there is evidence that a male equivalent of PCOS may exists, we ask whether sons born to mothers with PCOS (PCOS-sons) transmit reproductive and metabolic phenotypes to their male progeny. Here, in a register-based cohort and a clinical case-control study, we find that PCOS-sons are more often obese and dyslipidemic. Our prenatal androgenized PCOS-like mouse model with or without diet-induced obesity confirmed that reproductive and metabolic dysfunctions in first-generation (F<sub>1</sub>) male offspring are passed down to F<sub>3</sub>. Sequencing of F<sub>1</sub>-F<sub>3</sub> sperm reveals distinct differentially expressed (DE) small non-coding RNAs (sncRNAs) across generations in each lineage. Notably, common targets between transgenerational DEsncRNAs in mouse sperm and in PCOS-sons serum indicate similar effects of maternal hyperandrogenism, strengthening the translational relevance and highlighting a previously underappreciated risk of transmission of reproductive and metabolic dysfunction via the male germline.
Medical subject headings
- Polycystic Ovary Syndrome