ABSTRACT: Polycystic ovarian syndrome (PCOS) is the most common gynaecological endocrine disease in women of reproductive age, with a prevalence rate of more than 12%, and is characterised by sporadic ovulation or anovulation, hyperandrogenism and polycystic ovarian changes. Polycystic ovary syndrome has a complex clinical presentation and, in addition to affecting follicular development and reproductive endocrine levels in women of childbearing age, it also impairs early embryonic development, affecting pregnancy outcome and offspring health, but its pathogenesis is unclear. In this study, we constructed a mouse model of PCOS using late-gestational hyperandrogen exposure, and examined the reproductive endocrine phenotype and glycolipid metabolism phenotype in mice. We found that PCOS model mice exposed to dihydrotestosterone in late pregnancy could exhibit hyperandrogenic manifestations, presenting elevated vaginal-anal index and delayed puberty establishment, as well as disturbed estrous cycle in adulthood. Ovulation number, number of mature oocytes, fertilisation rate and number of blastocysts were significantly lower in PCOS model mice compared to control mice. Subsequently, we assessed the follicular development and embryonic development ability of the mice using superovulation and in vitro fertilisation experiments, and obtained preimplantation embryonic RNA expression profiles of PCOS mice by performing Smart-seqII RNA sequencing to explore the possible mechanisms by which PCOS affects preimplantation embryonic development and offspring health. Bioinformatics analyses showed that 160 differentially expressed genes were identified out of 12,165 genes in blastocyst samples from both groups of mice, of which calcium/calmodulin-dependent protein kinase II β (CAMK2B2), melanoma-associated antigen B2 (MAGEB2), and the ADAM metallopeptidase domain (Adam4) were significantly differentially between the polycystic ovary syndrome and control groups Expression. Functional enrichment analyses revealed that the differential genes were mainly associated with pathways such as glandular development, nephron development, organ development and receptor catabolism. Our current study highlights the deleterious effects of intrauterine exposure to hyperandrogenism on the expression of polycystic ovary syndrome in mice, as well as resulting in impaired development of their eggs and early embryos. These findings may provide valuable insights into the early prevention of polycystic ovary syndrome.
