Prenatally androgenized PCOS mice have ovary-independent uterine dysfunction and placental inflammation aggravated by high-fat diet - UTU Research Portal

A1 Refereed original research article in a scientific journal

Prenatally androgenized PCOS mice have ovary-independent uterine dysfunction and placental inflammation aggravated by high-fat diet

Authors: Luyckx, Lena; Myllykangas, Milena; Saarela, Ulla; Virtanen, Nikke; Hurskainen, Elisa; Savolainen, Audrey; Ollikainen, Nadja; Norlén, Anna-Karin; Ohlsson, Claes; Poutanen, Matti; Velde, Greetje Vande; Arffman, Riikka K.; Prunskaite-Hyyryläinen, Renata; Vriens, Joris; Piltonen, Terhi T.

Publisher: AMER ASSOC ADVANCEMENT SCIENCE

Publishing place: WASHINGTON

Publication year: 2025

Journal: Science Advances

Journal name in source: SCIENCE ADVANCES

Journal acronym: SCI ADV

Article number: eadu3699

Volume: 11

Issue: 19

Number of pages: 15

ISSN: 2375-2548

eISSN: 2375-2548

DOI: https://doi.org/10.1126/sciadv.adu3699

Web address : https://doi.org/10.1126/sciadv.adu3699

Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/498669516

Abstract

Polycystic ovary syndrome (PCOS) is a common hyperandrogenic and metabolic condition in women. The syndrome is linked to subfertility and pregnancy complications, yet the independent effects of exposure to hyperandrogenism and obesity on endometrial function remain unclear. Here, PCOS-like mice were generated using prenatal androgenization (PNA) with dihydrotestosterone, followed by a prepubertal high-fat (HF) or standard diet. In ovariectomized mice, PNA impaired uterine closure during the implantation window, disrupted decidualization, and altered extracellular matrix- and inflammation-related gene expression. The effects were aggravated by the HF diet. In naturally mated, ovary-intact mice, PNA and HF diet affected decidual and placental gene expression, suggestive of placental dysfunction and inflammation, and induced fetal growth restriction. This study underlines the role of the uterus in adverse pregnancy outcomes in PCOS and identifies possible underlying mechanisms for future studies. Prepregnancy interventions targeting metabolic health and hyperandrogenism should be the next steps to optimize PCOS pregnancy outcomes.

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Funding information in the publication:
This work was supported by the Horizon 2020 Marie-Curie MATER Innovative Training Network [813707 (T.T.P.)], the Oulu Scholarship Foundation Grant (L.L.), the Jusélius Foundation (T.T.P.), the Novo Nordisk Foundation [NNF21OC0070372 (T.T.P.)], the Research Council of Finland [315921, 321763, and 336449 (R.K.A. and T.T.P.)], and Fonds Wetenschappelijk Onderzoek [I006524N and G0A6719N (G.V.V. and J.V.)].