Hyperandrogenism and Insulin Resistance Modulate Gravid Uterine and Placental Ferroptosis in PCOS-Like Rats

    June 2020 in “ Journal of Endocrinology ”
    Yuehui Zhang, Min Hu, Wenyan Jia, Guoqi Liu, Jiao Zhang, Bing Wang, Juan Li, Peng Cui, Xin Li, Susanne Lager, Amanda N. Sferruzzi‐Perri, Yanhua Han, Songjiang Liu, Xiaoke Wu, Mats Brännström, Ruijin Shao, Håkan Billig
    TLDR Hyperandrogenism and insulin resistance in PCOS-like rats can lead to pregnancy complications due to increased cell death in the uterus and placenta.
    The study investigated the effects of hyperandrogenism and insulin resistance on ferroptosis in the gravid uterus and placenta of PCOS-like rats, using 39 female rats. Exposure to 5α-dihydrotestosterone (DHT) and insulin led to decreased GPX4 and glutathione levels, increased oxidative stress, and altered ferroptosis-related gene expression, particularly in the uterus. These changes contributed to fetal loss, with apoptosis and necroptosis also playing compensatory roles. The study highlighted the complex interactions between hyperandrogenism, insulin resistance, and cell death pathways, suggesting potential impacts on pregnancy outcomes in PCOS.
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