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Primordial follicles, each composed of a single oocyte surrounded by somatic cells, are the only source of gametes during the entire reproductive lifespan of the female. The size of the initial follicle pool is a key component in determining reproductive longevity, and impaired follicle assembly has severe consequences for fertility. Here, we evaluate the effect of zinc deficiency on germ cell survival and follicle activation in late pregnancy and early postnatally using in vitro organ culture of mouse ovaries. Zinc deficiency did not affect apoptosis, germ cell number, and gene expression in fetal ovaries. Germ cell nest breakdown, which occurs in the newborn mouse ovary, involves invasion of germ cell cysts by somatic cells to form primordial follicles was disrupted by zinc deficiency leading to fewer oocytes enclosed in follicles (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.002). Gene expression of both an oocyte\u2010specific factor (\n                    <jats:italic>Bmp15<\/jats:italic>\n                    ) and granulosa cell\u2013specific factor (\n                    <jats:italic>Foxl2<\/jats:italic>\n                    ) shown to regulate nest breakdown was decreased by zinc deficiency (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). There was also a strong trend toward fewer activated growing follicles after zinc\u2010deficient culture of newborn ovaries (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.051). The initial wave of follicle activation is key for both paracrine and endocrine signaling from the ovary. Disruption of this process, as well as impaired primordial follicle formation, may impact subsequent fertility.\n                  <\/jats:p>","DOI":"10.1002\/mrd.70092","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:05:34Z","timestamp":1770908734000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Zinc Deficiency Disrupts Germ Cell Nest Breakdown During In Vitro Ovary Culture"],"prefix":"10.1002","volume":"93","author":[{"given":"James M.","family":"Hester","sequence":"first","affiliation":[{"name":"Integrative and Biomedical Physiology Program The Pennsylvania State University University Park Pennsylvania USA"},{"name":"Department of Animal Science The Pennsylvania State University University Park Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne M.","family":"Getman","sequence":"additional","affiliation":[{"name":"Department Biology Syracuse University Syracuse New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa E.","family":"Pepling","sequence":"additional","affiliation":[{"name":"Department Biology Syracuse University Syracuse New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Diaz","sequence":"additional","affiliation":[{"name":"Integrative and Biomedical Physiology Program The Pennsylvania State University University Park Pennsylvania USA"},{"name":"Department of Animal Science The Pennsylvania State University University Park Pennsylvania 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