Prenatal exposure to benzo[a]pyrene depletes ovarian reserve and masculinizes embryonic ovarian germ cell transcriptome transgenerationally II

People are exposed to polycyclic aromatic hydrocarbons, like benzo[a]pyrene (BaP), via inhalation of particulate matter air pollution and ingestion of grilled and smoked foods. Prenatal exposure to BaP destroys germ cells in ovaries, causing earlier onset of ovarian senescence post-natally. Developing testes are affected at higher doses than ovaries. However, it is not known if adverse effects are transmitted to subsequent generations. We orally dosed pregnant female mice (F0) with 0.033, 0.2, or 2 mg/kg-day BaP or vehicle from embryonic day (E) 6.5-11.5 (F1 offspring) or E6.5-15.5 (F2 and F3). Ovarian germ cell and follicle numbers were significantly decreased in F3 females at all doses of BaP; testicular germ cells were not affected. E13.5 germ cell RNA-sequencing revealed significantly increased expression of male-specific genes in female germ cells across generations and BaP doses. Our study demonstrated that F0 BaP exposure partially disrupted sexual identity of female germ cells transgenerationally. Whole genome bisulfite sequencing of FACS-enriched mouse primordial germ cells with or without gestational exposure to banzo[a]pyrene: Repeated Experiment