Transgenerational transmission of reproductive and metabolic dysfunction in the male progeny of polycystic ovary syndrome

• 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 (F1) male offspring are passed down to F3. Sequencing of F1–F3 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. 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

adipose tissue

male offspring

male offspring to male germline

maternal hyperandrogenism

maternal obesity

polycystic ovary syndrome

small non-coding RNAs

sperm

transgenerational transmission

Animals

Case-Control Studies

Female

Humans

Male

Mice

Obesity

Pregnancy

Reproduction

Semen

small untranslated RNA

animal experiment

animal model

animal tissue

Article

case control study

childhood obesity

cohort analysis

controlled study

differential gene expression

dyslipidemia

fetus outcome

fetus risk

gene locus

genetic risk

genital system disease

germ line

high risk infant

high risk patient

human

hyperandrogenism

maternal fetal transmission

metabolic disorder

mouse

nonhuman

ovary polycystic disease

prenatal exposure

progeny

risk assessment

RNA analysis

vertical transmission

animal

genetics

Translationell medicin TRIM

Translational Medicine TRIM

prenatal androgen exposure

women

inheritance

brothers

disease

sons

susceptibility

micrornas

genetics

pathway

Cell Biology

Research & Experimental Medicine

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)