Obesity alters the ovarian proteomic response to zearalenone exposure

• Autor: González-Alvarez, M. Estefanía ; McGuire, Bailey C. ; Keating, Aileen F.
• Assuntos: Animals ; Biotransformation ; BRCA1 protein ; chemical metabolism ; Cytochrome P-450 ; DNA damage ; DNA damage repair ; DNA repair ; DNMT1 protein ; Estrogens, Non-Steroidal - adverse effects ; Estrus cycle ; Female ; Follicles ; Glutathione transferase ; Kidneys ; Methyltransferases ; Mice ; Mycotoxins - adverse effects ; Obesity ; ovarian proteome ; Ovaries ; ovary ; Ovary - drug effects ; Ovary - metabolism ; Progesterone ; Proteins ; Proteome - metabolism ; RESEARCH ARTICLE ; Spleen ; Uterus ; Xenoestrogens ; Zearalenone ; Zearalenone - adverse effects
• É parte de: Biology of reproduction, 2021-07, Vol.105 (1), p.278-289
• Descrição: 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 γ H2AX 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.
  
• Editor: United States: Society for the Study of Reproduction
  
• Idioma: Inglês