Gestational exposure to phenanthrene induces follicular atresia and endocrine dyscrasia in F1 adult female

Epidemiological investigations and animal studies demonstrate a significantly positive relationship between polycyclic aromatic hydrocarbons (PAHs) exposure and reproductive disorders. However, few researches are focused on the reproductive toxicity of low-molecular-weight PAHs (number of benzene ring ≤ 3) which occupy a large part of PAHs. Phenanthrene (Phe), a typical low-molecular-weight PAH, is one of the most abundant PAHs detected in foods. In the present study, oral treatment with Phe at a human exposure related level during gestation (60 μg/kg body weight every three days, six times in total) induced reproductive disorders in F1 adult female mice: the number of antral follicles (an immature stage of follicular development) were significantly increased, while the maturation of oocytes was inhibited and aggravated follicular atresia was observed; the serum levels of luteinizing hormone (LH), testosterone and estradiol were significantly reduced; the receptor of follicle-stimulating hormone (FSHR) and aromatase in the ovary were significantly upregulated; transcriptome analysis demonstrated that the phosphatidylinositol 3-kinase and protein kinase B (PI3K/Akt) signal pathway was upregulated, and the calcium signal pathway was disturbed, which probably accounts for the exacerbated atresia of the growing follicles and the excessive consumption of follicles. The reproductive toxicity of low-molecular-weight PAHs could not be neglected. [Display omitted] •In-utero exposure to phenanthrene induced atresia of follicle in F1 adult female.•In vitro exposure to phenanthrene inhibits the oocytes maturation.•The ovarian follicles were aberrantly activated via upregulating PI3K/Akt signal.•Serum estradiol levels were decreased via diminished LH and FSH signal in ovary.•Disordered calcium signaling might account for the exacerbated follicles atresia.