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...

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Bibliographic Details
Published in:Biology of reproduction 2021-07, Vol.105 (1), p.278-289
Main Authors: González-Alvarez, M. Estefanía, McGuire, Bailey C., Keating, Aileen F.
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:0006-3363
1529-7268
1529-7268
DOI:10.1093/biolre/ioab069