Obesity alters the ovarian proteomic response to zearalenone exposure†.

Zearalenone (ZEN), a nonsteroidal estrogenic mycotoxin, is detrimental to female reproduction. Altered chemical biotransformation, depleted primordial follicles and a blunted genotoxicant response have been discovered in obese female ovaries, thus, this study investigated the hypothesis that obesity would enhance ovarian sensitivity to ZEN exposure. Seven-week-old female wild-type nonagouti KK.Cg-a/a mice (lean) and agouti lethal yellow KK.Cg-Ay/J mice (obese) received food and water ad libitum, and either saline or ZEN (40 µg/kg) per os for 15 days. Body and organ weights, and estrous cyclicity were recorded, and ovaries collected posteuthanasia for protein analysis. Body and liver weights were increased (P < 0.05) in the obese mice, but obesity did not affect (P > 0.05) heart, kidney, spleen, uterus, or ovary weight and there was no impact (P > 0.05) of ZEN exposure on body or organ weight in lean or obese mice. Obese mice had shorter proestrus (P < 0.05) and a tendency (P = 0.055) for longer metestrus/diestrus. ZEN exposure in obese mice increased estrus but shortened metestrus/diestrus length. Neither obesity nor ZEN exposure impacted (P > 0.05) circulating progesterone, or ovarian abundance of EPHX1, GSTP1, CYP2E1, ATM, BRCA1, DNMT1, HDAC1, H4K16ac, or H3K9me3. Lean mice exposed to ZEN had a minor increase in γH2AX abundance (P < 0.05). In lean and obese mice, LC-MS/MS identified alterations to proteins involved in chemical metabolism, DNA repair and reproduction. These data identify ZEN-induced adverse ovarian modes of action and suggest that obesity is additive to ZEN-induced ovotoxicity.

Absence of glyphosate-induced effects on ovarian folliculogenesis and steroidogenesis.

Glyphosate (GLY) is an herbicidal active ingredient and both in vitro and in vivo studies suggest that GLY alters ovarian function. To determine if a chronic GLY exposure model affected steroidogenesis or folliculogenesis in vivo, postnatal day 42 C57BL6 female mice were orally delivered vehicle control (saline) or GLY (2 mg/Kg) from a pipette tip five days per week for either five or ten weeks. Mice were euthanized at the pro-estrus stage of the estrous cycle. GLY exposure did not impact body weight gain, organ weights, or healthy follicle numbers. In addition, GLY exposure did not affect abundance of ovarian mRNA encoding kit ligand (Kitlg), KIT proto-oncogene receptor tyrosine kinase (c-Kit), insulin receptor (Insr), insulin receptor substrate (Irs1 or Irs2) and protein thymoma viral proto-oncogene 1 (AKT) or phosphorylated AKT. Ovarian mRNA or protein abundance of Star, 3ß-hydroxysteroid dehydrogenase (Hsd3b1), Cyp11a1 or Cyp19a were also not altered by GLY. Circulating 17ß-estradiol and progesterone concentration were unaffected by GLY exposure. In conclusion, chronic GLY exposure for five or ten weeks did not affect the ovarian endpoints examined herein.