Han Shan, Lv Jiale, Sun Xuedong, Xie Yanqiu, Shi Yuhua
Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Department of Reproductive Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Front Cell Dev Biol. 2025 May 2;13:1554437. doi: 10.3389/fcell.2025.1554437. eCollection 2025.
Polycystic ovary syndrome (PCOS) is a complex disorder that originates during fetal development and significantly impairs female fertility during the reproductive years. Although it is hypothesized that prenatal exposure to elevated androgen levels plays a crucial role in the pathogenesis of PCOS, the precise effects of such exposure on the offspring of individuals with PCOS remain unclear. In this study, we established a mouse model of PCOS by administering dihydrotestosterone (DHT) prenatally. We subsequently evaluated the reproductive phenotype and fertility of the PCOS-like mice, focusing on ovarian function and embryo developmental potential. Smart-seqII RNA sequencing was performed on blastocysts to obtain the RNA expression profile of preimplantation embryos from PCOS mice. These findings indicate that the PCOS model mice exhibit hyperandrogenic symptoms, reduced ovulation rates, and impaired development of oocytes and blastocysts compared to controls. Furthermore, 918 differentially expressed genes were identified in the blastocyst samples, with significant enrichment in pathways related to intracellular energy metabolism, tissue development, glycolipid metabolism, hormone synthesis, and inflammation. This research presents direct evidence that prenatal exposure to hyperandrogenism negatively influences the early embryonic development of offspring and plays a significant role in the later manifestation of polycystic ovary syndrome in adulthood. These findings contribute valuable insights for the early prevention of PCOS.
多囊卵巢综合征（PCOS）是一种复杂的疾病，起源于胎儿发育阶段，在生殖年龄期间显著损害女性生育能力。尽管据推测，产前暴露于升高的雄激素水平在PCOS的发病机制中起关键作用，但这种暴露对PCOS患者后代的确切影响仍不清楚。在本研究中，我们通过产前给予二氢睾酮（DHT）建立了PCOS小鼠模型。随后，我们评估了类PCOS小鼠的生殖表型和生育能力，重点关注卵巢功能和胚胎发育潜力。对囊胚进行了Smart-seqII RNA测序，以获得PCOS小鼠植入前胚胎的RNA表达谱。这些发现表明，与对照组相比，PCOS模型小鼠表现出高雄激素症状、排卵率降低以及卵母细胞和囊胚发育受损。此外，在囊胚样本中鉴定出918个差异表达基因，这些基因在与细胞内能量代谢、组织发育、糖脂代谢、激素合成和炎症相关的通路中显著富集。本研究提供了直接证据，表明产前暴露于高雄激素血症会对后代的早期胚胎发育产生负面影响，并在成年期多囊卵巢综合征的后期表现中起重要作用。这些发现为PCOS的早期预防提供了有价值的见解。
