Neonatal exposure to an environmentally relevant phthalate mixture alters ovarian function in mice

Phthalates are synthetic chemical compounds commonly used in consumer products. Neonates are often exposed to phthalate mixtures, but the effects of neonatal exposure to phthalate mixtures on ovarian health are unclear. Thus, this study tested the hypothesis that neonatal exposure to an environmentally relevant phthalate mixture alters neonatal ovarian function by disrupting steroidogenesis and cell cycle regulation and promoting inflammation, oxidative stress, and apoptosis. CD-1 neonatal mice were orally dosed with corn oil or a phthalate mixture (10, 20, 100 μg/kg/day) daily from post-natal day (PND) 3 to PND 8. Sera and ovaries were collected on PND 8 and PND 10 to quantify follicle numbers and to measure phthalate metabolites, protein levels, and expression of key markers involved in ovarian health. At PND 8, neonatal exposure to the mixture increased the levels of the phthalate metabolites (mono-ethyl phthalate and mono(2-ethylhexyl) phthalate) and C-reactive protein in the sera and it decreased the number of primordial follicles and ovarian expression of Il1-r2. Additionally, the mixture increased the expression of steroidogenic regulators (Cyp17a1 and Lhcgr) and a pro-apoptotic factor (Bad) in comparison to controls. At PND 10, the mixture decreased the number of primordial follicles and the expression of Cyp17a1, Bad, Bax, Fas, and Cdkn1a, and increased expression of Lhcgr, Fshr, and Bcl2l10 in comparison to controls. Collectively, these data indicate that neonatal exposure to an environmentally relevant phthalate mixture decreases the health of the neonatal ovary.