10X Genomics Multiome Assay (GEX + ATAC) of hypothalamic preoptic area in prenatally androgenized and control prepubertal female mice.

Polycystic ovary syndrome (PCOS) is the most common cause of infertility in women. The etiology of PCOS is not well understood. Both genetics and early life exposures are considered contributing factors. Women with PCOS have elevated androgens, potentially exposing female offspring to high androgens in utero. Daughters of women with PCOS are at increased risk of developing this disorder. Prenatal androgenization (PNA) of several species, including mice, recapitulates many phenotypes observed in PCOS. Adult female PNA mice exhibit elevated luteinizing hormone (LH) levels and increased gonadotropin-releasing hormone (GnRH) neuron pulse frequency. These changes in GnRH neurons emerge during the pubertal transition. We utilized the 10X Genomics Multiome (gene expression and ATAC-seq) assay to investigate changes in both gene expression and chromatin accessibility in the hypothalamic preoptic area of prepubertal (postnatal day 21) control and PNA females. Through analysis of ~51,000 cells across 34 cell populations, we identified cell-type-specific chromatin remodeling in response to prenatal androgen exposure, despite the absence of coordinated transcriptional changes at postnatal day 21, suggesting that critical developmental programming occurs earlier with persistent epigenetic consequences.