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The ZEB1 transcription factor is a conserved target of both families and has been implicated as a key player in female fertility at multiple levels. Using gene-edited mice that express a miR-200a\/b-resistant form of Zeb1, we found that derepression of Zeb1 in the female pituitary caused decreased production of luteinizing hormone and anovulatory infertility. These phenotypes were accompanied by widespread changes in pituitary gene expression characterized by decreased levels of ZEB1 targets, which include the miR-200a\/b microRNAs (miRNAs), as expected from the miR-200a\/b\u2013ZEB1 double-negative feedback loop. Also observed were increased levels of mesenchymal genes, neuronal genes, and miR-200a\/b targets. These results show that a double-negative feedback loop centered on the miRNA regulation of a single transcription factor can significantly influence the expression of thousands of genes and have dramatic phenotypic consequences.<\/jats:p>","DOI":"10.1093\/nar\/gkaf1357","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T12:54:33Z","timestamp":1766494473000},"source":"Crossref","is-referenced-by-count":2,"title":["Derepression of a single microRNA target causes female infertility in mice"],"prefix":"10.1093","volume":"54","author":[{"given":"Joanna","family":"Stefano","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute , Cambridge, MA 02142 ,","place":["United States"]},{"name":"Whitehead Institute for Biomedical Research , Cambridge, MA 02142 ,","place":["United States"]},{"name":"Department of Biology, Massachusetts Institute of Technology , Cambridge, MA 02139 ,","place":["United 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Biology, Massachusetts Institute of Technology , Cambridge, MA 02139 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3872-2856","authenticated-orcid":false,"given":"David P","family":"Bartel","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute , Cambridge, MA 02142 ,","place":["United States"]},{"name":"Whitehead Institute for Biomedical Research , Cambridge, MA 02142 ,","place":["United States"]},{"name":"Department of Biology, Massachusetts Institute of Technology , Cambridge, MA 02139 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0333-3586","authenticated-orcid":false,"given":"Benjamin","family":"Kleaveland","sequence":"additional","affiliation":[{"name":"Department of Pathology and Lab Medicine, Weill Cornell Medicine , New York , NY 10065 ,","place":["United 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