{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:37:55Z","timestamp":1792132675822,"version":"4.4.0"},"reference-count":73,"publisher":"The Company of Biologists","issue":"19","license":[{"start":{"date-parts":[[2000,10,1]],"date-time":"2000-10-01T00:00:00Z","timestamp":970358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The functions of estrogen receptors (ERs) in mouse ovary and genital tracts were investigated by generating null mutants for ER\u03b1 (ER\u03b1KO), ER\u03b2 (ER\u03b2KO) and both ERs (ER\u03b1\u03b2KO). All ER\u03b1KO females are sterile, whereas ER\u03b2KO females are either infertile or exhibit variable degrees of subfertility. Mast cells present in adult ER\u03b1KO and ER\u03b1\u03b2KO ovaries could participate in the generation of hemorrhagic cysts. Folliculogenesis proceeds normally up to the large antral stage in both ER\u03b1KO and ER\u03b2KO adults, whereas large antral follicles of ER\u03b1+\/\u2212\/ER\u03b2KO and ER\u03b1\u03b2KO adults are markedly deficient in granulosa cells. Similarly, prematurely developed follicles found in prepubertal ER\u03b1KO ovaries appear normal, but their ER\u03b1\u03b2KO counterparts display only few granulosa cell layers. Upon superovulation treatment, all prepubertal ER\u03b1KO females form numerous preovulatory follicles of which the vast majority do not ovulate. The same treatment fails to elicit the formation of preovulatory follicles in half of the ER\u03b2KO mice and in all ER\u03b1+\/\u2212\/ER\u03b2KO mice. These and other results reveal a functional redundancy between ER\u03b1 and ER\u03b2 for ovarian folliculogenesis, and strongly suggest that (1) ER\u03b2 plays an important role in mediating the stimulatory effects of estrogens on granulosa cell proliferation, (2) ER\u03b1 is not required for follicle growth under wild type conditions, while it is indispensable for ovulation, and (3) ER\u03b1 is also necessary for interstitial glandular cell development. Our data also indicate that ER\u03b2 exerts some function in ER\u03b1KO uterus and vagina. ER\u03b1\u03b2KO granulosa cells localized within degenerating follicles transform into cells displaying junctions that are unique to testicular Sertoli cells. From the distribution pattern of anti-M\u00fcllerian hormone (AMH) in ER\u03b1\u03b2KO ovaries, it is unlikely that an elevated AMH level is the cause of Sertoli cell differentiation. Our results also show that cell proliferation in the prostate and urinary bladder of old ER\u03b2KO and ER\u03b1\u03b2KO males is apparently normal.<\/jats:p>","DOI":"10.1242\/dev.127.19.4277","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T04:16:47Z","timestamp":1619410607000},"page":"4277-4291","source":"Crossref","is-referenced-by-count":890,"title":["Effect of single and compound knockouts of estrogen receptors \u03b1 (ER\u03b1) and \u03b2 (ER\u03b2) on mouse reproductive phenotypes"],"prefix":"10.1242","volume":"127","author":[{"given":"Sonia","family":"Dupont","sequence":"first","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, CNRS\/INSERM\/ULP, Coll\u00e8ge de France, BP 163, 67404 Illkirch-Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9e","family":"Krust","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, CNRS\/INSERM\/ULP, Coll\u00e8ge de France, BP 163, 67404 Illkirch-Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Gansmuller","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, CNRS\/INSERM\/ULP, Coll\u00e8ge de France, BP 163, 67404 Illkirch-Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9e","family":"Dierich","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, CNRS\/INSERM\/ULP, Coll\u00e8ge de France, BP 163, 67404 Illkirch-Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Chambon","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, CNRS\/INSERM\/ULP, Coll\u00e8ge de France, BP 163, 67404 Illkirch-Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Mark","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, CNRS\/INSERM\/ULP, Coll\u00e8ge de France, BP 163, 67404 Illkirch-Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2000,10,1]]},"reference":[{"key":"2024011016403253600_DEVELOP_127_19_4277C1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/0378-1119(87)90214-9","article-title":"Cloning and expression of the mouse pgk-1 gene and the nucleotide sequence of its promoter","volume":"60","author":"Adra","year":"1987","journal-title":"Gene"},{"key":"2024011016403253600_DEVELOP_127_19_4277C2","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1139\/o94-070","article-title":"Expression of clusterin in cell differentiation and cell death","volume":"72","author":"Ahuja","year":"1994","journal-title":"Biochem. 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