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• W2019094666 endingPage "886" @default.
• W2019094666 startingPage "873" @default.
• W2019094666 abstract "Shortly before ovulation, the oocyte acquires developmental competence and granulosa cells undergo tremendous changes including cumulus expansion and luteinization. Zinc is emerging as a key regulator of meiosis in vitro, but a complete understanding of zinc-mediated effects during the periovulatory period is lacking. The present study uncovers the previously unknown role of zinc in maintaining meiotic arrest before ovulation. A zinc chelator [N,N,N′,N′-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN)] caused premature germinal vesicle breakdown and associated spindle defects in denuded oocytes even in the presence of a phosphodiesterase 3A inhibitor (milrinone). TPEN also potently blocked cumulus expansion by blocking induction of expansion-related transcripts Has2, Ptx3, Ptgs2, and Tnfaip6 mRNA. Both meiotic arrest and cumulus expansion were rescued by exogenous zinc. Lack of cumulus expansion is due to an almost complete suppression of phospho-Sma- and Mad-related protein 2/3 signaling. Consistent with a decrease in phospho-Sma- and Mad-related protein 2/3 signaling, TPEN also decreased cumulus transcripts (Ar and Slc38a3) and caused a surprising increase in mural transcripts (Lhcgr and Cyp11a1) in cumulus cells. In vivo, feeding a zinc-deficient diet for 10 d completely blocked ovulation and compromised cumulus expansion. However, 42.5% of oocytes had prematurely resumed meiosis before human chorionic gonadotropin injection, underscoring the importance of zinc before ovulation. A more acute 3-d treatment with a zinc-deficient diet did not block ovulation but did increase the number of oocytes trapped in luteinizing follicles. Moreover, 23% of ovulated oocytes did not reach metaphase II due to severe spindle defects. Thus, acute zinc deficiency causes profound defects during the periovulatory period with consequences for oocyte maturation, cumulus expansion, and ovulation." @default.
• W2019094666 created "2016-06-24" @default.
• W2019094666 creator A5029291297 @default.
• W2019094666 creator A5069575062 @default.
• W2019094666 date "2012-02-01" @default.
• W2019094666 modified "2023-10-15" @default.
• W2019094666 title "Zinc Depletion Causes Multiple Defects in Ovarian Function during the Periovulatory Period in Mice" @default.
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• W2019094666 doi "https://doi.org/10.1210/en.2011-1599" @default.
• W2019094666 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3275394" @default.
• W2019094666 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22147014" @default.
• W2019094666 hasPublicationYear "2012" @default.
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