{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:21:27Z","timestamp":1772983287647,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:00:00Z","timestamp":1768003200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Development, Growth &amp;amp; Differentiation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In medaka (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Oryzias latipes<\/jats:italic>\n                    <\/jats:styled-content>\n                    ), the first morphological sex difference is germ cell number before hatching, which is determined by the\n                    <jats:italic>dmy<\/jats:italic>\n                    gene on the Y chromosome. This study aimed to clarify whether zygotically synthesized estrogen influences the kinetics of germ cell number during early gonadal sex differentiation. We established disruptive mutants of the estrogen\u2010synthesizing enzyme aromatase by knocking out\n                    <jats:italic>cyp19a1a<\/jats:italic>\n                    (\u0394\n                    <jats:italic>cyp19a1a<\/jats:italic>\n                    ) and\n                    <jats:italic>cyp19a1b<\/jats:italic>\n                    (\u0394\n                    <jats:italic>cyp19a1b<\/jats:italic>\n                    ) as well as double disruptive mutants (\u0394cyp19a1s DKO) from each individual knockout using CRISPR\/Cas9. \u0394cyp19a1s DKO XY and XX adult fish at 90\u2009days post\u2010hatching (dph) exhibited basal levels of estradiol\u201017\u03b2. At hatching (0\u2009dph: stage 39), WT XX fry had significantly more germ cells than WT XY fry, and gonial cells were the most advanced germ cell stage across both sexes. Germ cell number and gonadal histology in \u0394cyp19a1s DKO mutants resembled those of WT fry. At 10\u2009dph, germ cell number and gonadal histology were also similar between WT and \u0394cyp19a1s XY fry. In \u0394cyp19a1s DKO XX fry, diplotene oocytes and the total number of germ cells were significantly lower compared with WT. Exposure to 17\u03b1\u2010ethynylestradiol rescued the reduction in diplotene oocytes in \u0394cyp19a1s DKO mutants to levels comparable to the control, resulting in the rescue of total germ cell number. Overall, our findings suggest that zygotically synthesized estrogen does not affect sex differences in germ cell number as the initial morphological sex difference but partly facilitates the differentiation from pachytene to diplotene oocytes.\n                  <\/jats:p>","DOI":"10.1111\/dgd.70038","type":"journal-article","created":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T09:56:19Z","timestamp":1768038979000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of\n                    <i>cyp19a1a<\/i>\n                    and\n                    <i>cyp19a1b<\/i>\n                    Knockout on Germ Cell Kinetics During Gonadal Sex Differentiation in Medaka"],"prefix":"10.1111","volume":"68","author":[{"given":"Yuta","family":"Sakai\u2010Yamada","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Reproductive Biology, Institute for Environmental Sciences University of Shizuoka  Shizuoka Japan"},{"name":"Graduate School of Pharmaceutical and Nutritional Sciences University of Shizuoka  Shizuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taijun","family":"Myosho","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Reproductive Biology, Institute for Environmental Sciences University of Shizuoka  Shizuoka Japan"},{"name":"Graduate School of Pharmaceutical and Nutritional Sciences University of Shizuoka  Shizuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4968-1260","authenticated-orcid":false,"given":"Tohru","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Reproductive Biology, Institute for Environmental Sciences University of Shizuoka  Shizuoka Japan"},{"name":"Graduate School of Pharmaceutical and Nutritional Sciences University of Shizuoka  Shizuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/6.6.554"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2004.11.020"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0044\u20108486(02)00057\u20101"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00206337"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1897\/03\u2010610.1"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1020068224909"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.23860"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2016.07.022"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2014.04.036"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1680001"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.09.112"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mod.2004.03.012"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jez.a.120"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aaf.2023.02.006"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.2.7928"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20158"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609932104"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep37357"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003\u20100035"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature751"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.1c06729"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00044.2019"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.07.013"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007259"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.20497"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010\u20100812"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.180.4089.963"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.07.039"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.21.4645"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.2108\/zsj\/22.791"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2014.10.011"},{"key":"e_1_2_11_33_1","first-page":"171","article-title":"Origin and Destination of the Median Germ Cells in Late Somite Stage and Early Post\u2010Somite Stage Duck Embryos","volume":"13","author":"Limborgh J.","year":"1975","journal-title":"Acta Morphologica Neerlando\u2010Scandinavica"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2023.162740"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010023\u201005551\u20101"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep19738"}],"container-title":["Development, Growth &amp; Differentiation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dgd.70038","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dgd.70038","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dgd.70038","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T09:07:29Z","timestamp":1772960849000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/dgd.70038"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/dgd.70038"],"URL":"https:\/\/doi.org\/10.1111\/dgd.70038","archive":["Portico"],"relation":{},"ISSN":["0012-1592","1440-169X"],"issn-type":[{"value":"0012-1592","type":"print"},{"value":"1440-169X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-08-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70038"}}