{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T02:33:25Z","timestamp":1770086005921,"version":"3.49.0"},"reference-count":87,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006049","name":"Comisi\u00f3n Sectorial de Investigaci\u00f3n Cient\u00edfica","doi-asserted-by":"publisher","award":["22320200200186UD"],"award-info":[{"award-number":["22320200200186UD"]}],"id":[{"id":"10.13039\/501100006049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006049","name":"Comisi\u00f3n Sectorial de Investigaci\u00f3n Cient\u00edfica","doi-asserted-by":"publisher","award":["22320200200186UD"],"award-info":[{"award-number":["22320200200186UD"]}],"id":[{"id":"10.13039\/501100006049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006049","name":"Comisi\u00f3n Sectorial de Investigaci\u00f3n Cient\u00edfica","doi-asserted-by":"publisher","award":["22320200200186UD"],"award-info":[{"award-number":["22320200200186UD"]}],"id":[{"id":"10.13039\/501100006049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006049","name":"Comisi\u00f3n Sectorial de Investigaci\u00f3n Cient\u00edfica","doi-asserted-by":"publisher","award":["22320200200186UD"],"award-info":[{"award-number":["22320200200186UD"]}],"id":[{"id":"10.13039\/501100006049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008725","name":"Agencia Nacional de Investigaci\u00f3n e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["FCE_3_2022_1_172495"],"award-info":[{"award-number":["FCE_3_2022_1_172495"]}],"id":[{"id":"10.13039\/100008725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008725","name":"Agencia Nacional de Investigaci\u00f3n e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["FCE_3_2022_1_172495"],"award-info":[{"award-number":["FCE_3_2022_1_172495"]}],"id":[{"id":"10.13039\/100008725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008725","name":"Agencia Nacional de Investigaci\u00f3n e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["FCE_3_2022_1_172495"],"award-info":[{"award-number":["FCE_3_2022_1_172495"]}],"id":[{"id":"10.13039\/100008725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008725","name":"Agencia Nacional de Investigaci\u00f3n e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["FCE_3_2022_1_172495"],"award-info":[{"award-number":["FCE_3_2022_1_172495"]}],"id":[{"id":"10.13039\/100008725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Sex Differ"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Sex determination and differentiation are complex processes shaped by a wide variety of molecular factors. In contrast to teleost species, many aspects of these processes remain poorly understood in basal non-teleost fishes such as the Siberian sturgeon (\n                      <jats:italic>Acipenser baerii<\/jats:italic>\n                      ). Genetic sexing of this important aquaculture species now enables studies of undifferentiated males and females to identify factors involved in early sexual differentiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twelve undifferentiated Siberian sturgeon (six males, six females) were genetically sexed at 2.5 months of age. High-quality RNA was extracted from gonad samples, and transcriptomes were assembled using a reference dataset. Bioinformatic analyses were performed to identify sex-biased genes through differential expression analysis, Gene Ontology (GO) enriched terms, and classification of coding and non-coding sequences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Genes potentially associated with sex differentiation were identified in gonadal tissue. Female-biased genes included classical estrogens production genes (\n                      <jats:italic>hsd17b1<\/jats:italic>\n                      ,\n                      <jats:italic>cyp19a1<\/jats:italic>\n                      ,\n                      <jats:italic>foxl2<\/jats:italic>\n                      ) and immediate early response genes known to react rapidly to estrogens (\n                      <jats:italic>jun-b<\/jats:italic>\n                      ,\n                      <jats:italic>c-fos<\/jats:italic>\n                      ,\n                      <jats:italic>egr1<\/jats:italic>\n                      ), as well as genes not previously linked to estradiol (\n                      <jats:italic>di-ras2<\/jats:italic>\n                      ,\n                      <jats:italic>ier2<\/jats:italic>\n                      ,\n                      <jats:italic>aanat<\/jats:italic>\n                      ). The enriched Gene Ontology results suggested that melatonin signaling and hypothalamic pathways may also contribute to female differentiation. In males, the well-known factor\n                      <jats:italic>tbx1<\/jats:italic>\n                      was upregulated along with novel candidates (\n                      <jats:italic>plin1<\/jats:italic>\n                      ,\n                      <jats:italic>nrxn3<\/jats:italic>\n                      ,\n                      <jats:italic>chs2<\/jats:italic>\n                      ,\n                      <jats:italic>mmp9<\/jats:italic>\n                      ). No sex-biased genes related to androgen production were identified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      By 2.5 months of age, sex-specific gonadal differences are already apparent in Siberian sturgeon. This study highlights the estrogen response pathway, including immediate early response genes described here for the first time in the context of fish gonadal differentiation. At the same time, an estrogen-independent ovarian pathway cannot be ruled out. Male differentiation appears to involve\n                      <jats:italic>tbx1<\/jats:italic>\n                      together with new candidates for testis regulation in the absence of sex-biased androgen-producing enzymes. These novel genes expressed near the onset of sex differentiation merit further investigation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13293-025-00810-8","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T13:14:25Z","timestamp":1770038065000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-specific gonadal transcriptome during early development of Siberian sturgeon"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5420-5149","authenticated-orcid":false,"given":"Andr\u00e9","family":"Lasalle Gerla","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6438-9931","authenticated-orcid":false,"given":"Germ\u00e1n","family":"Benech-Correa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7126-5477","authenticated-orcid":false,"given":"Christophe","family":"Klopp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7529-7556","authenticated-orcid":false,"given":"Denise","family":"Vizziano-Cantonnet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"810_CR1","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.cub.2012.02.054","volume":"22","author":"T Gamble","year":"2012","unstructured":"Gamble T, Zarkower D. Sex determination. Curr Biol. 2012;22:257\u201362.","journal-title":"Curr Biol"},{"key":"810_CR2","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1080\/10641260802324610","volume":"16","author":"DJ Penman","year":"2008","unstructured":"Penman DJ, Piferrer F. Fish gonadogenesis. Part I: genetic and environmental mechanisms of sex determination. Rev Fish Sci. 2008;16:16\u201334.","journal-title":"Rev Fish Sci"},{"key":"810_CR3","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.ygcen.2009.03.002","volume":"165","author":"Y Guiguen","year":"2010","unstructured":"Guiguen Y, Fostier A, Piferrer F, Chang CF. Ovarian aromatase and estrogens: a pivotal role for gonadal sex differentiation and sex change in fish. Gen Comp Endocrinol. 2010;165:352\u201366.","journal-title":"Gen Comp Endocrinol"},{"key":"810_CR4","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1146\/annurev-animal-021122-113935","volume":"12","author":"J Kitano","year":"2024","unstructured":"Kitano J, Ansai S, Takehana Y, Yamamoto Y. Diversity and convergence of sex-determination mechanisms in teleost fish. Annul Rev Anim Biosci. 2024;12:233\u201359.","journal-title":"Annul Rev Anim Biosci"},{"key":"810_CR5","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1152\/physrev.00044.2019","volume":"101","author":"Y Nagahama","year":"2021","unstructured":"Nagahama Y, Chakraborty T, Paul-Prasanth B, Ohta K, Nakamura M. Sex determination, gonadal sex differentiation, and plasticity in vertebrate species. Physiol Rev. 2021;101:1237\u2013308.","journal-title":"Physiol Rev"},{"key":"810_CR6","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1080\/10641260802324644","volume":"16","author":"F Piferrer","year":"2008","unstructured":"Piferrer F, Guiguen Y. Fish gonadogenesis. Part II: molecular biology and genomics of sex differentiation. Rev Fish Sci. 2008;16:35\u201355.","journal-title":"Rev Fish Sci"},{"key":"810_CR7","doi-asserted-by":"crossref","unstructured":"Yamamoto Y, Luckenbach JA. Sex determination and gonadal sex differentiation. 2024.","DOI":"10.1016\/B978-0-323-90801-6.00052-5"},{"key":"810_CR8","doi-asserted-by":"crossref","unstructured":"Yamamoto T-O. Sex differentiation. Fish physiol. 1969;3:117\u2009\u2013\u200975.","DOI":"10.1016\/S1546-5098(08)60113-2"},{"key":"810_CR9","doi-asserted-by":"publisher","first-page":"e23729","DOI":"10.1002\/mrd.23729","volume":"91","author":"A Lasalle","year":"2024","unstructured":"Lasalle A, Benech-Correa G, Brunet FG, Vizziano\u2010Cantonnet D. hsd17b1 is a key gene for ovarian differentiation of the Siberian sturgeon. Mol Reprod Dev. 2024;91:e23729.","journal-title":"Mol Reprod Dev"},{"key":"810_CR10","doi-asserted-by":"publisher","first-page":"741735","DOI":"10.1016\/j.aquaculture.2024.741735","volume":"596","author":"D Vizziano-Cantonnet","year":"2025","unstructured":"Vizziano-Cantonnet D, Benech-Correa G, Lasalle-Gerla A. Estradiol-17\u03b2 but not 11\u03b2-hydroxyandrostenedione induces sex transdifferentiation in Siberian sturgeon. Aquaculture. 2025;596:741735.","journal-title":"Aquaculture"},{"key":"810_CR11","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/nrg1381","volume":"5","author":"J Brennan","year":"2004","unstructured":"Brennan J, Capel B. One tissue, two fates: molecular genetic events that underlie testis versus ovary development. Nat Rev Genet. 2004;5:509\u201321.","journal-title":"Nat Rev Genet"},{"key":"810_CR12","doi-asserted-by":"publisher","first-page":"119163","DOI":"10.1016\/j.gep.2020.119163","volume":"39","author":"Q Qi","year":"2021","unstructured":"Qi Q, Dong Z, Zhang N, Wang L, Shao C, Xu W. Cloning, expression and functional analysis of the desert Hedgehog (dhh) gene in Chinese tongue sole (Cynoglossus semilaevis). Gene Expr Patterns. 2021;39:119163.","journal-title":"Gene Expr Patterns"},{"key":"810_CR13","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.ygcen.2013.06.010","volume":"191","author":"B Crespo","year":"2013","unstructured":"Crespo B, Gomez A, Maz\u00f3n MJ, Carrillo M, Zanuy S. Isolation and characterization of Ff1 and Gsdf family genes in European sea bass and identification of early gonadal markers of precocious puberty in males. Gen Comp Endocrinol. 2013;191:155\u201367.","journal-title":"Gen Comp Endocrinol"},{"key":"810_CR14","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.gene.2010.10.014","volume":"472","author":"A Gautier","year":"2011","unstructured":"Gautier A, Le Gac F, Lareyre J-J. The Gsdf gene locus harbors evolutionary conserved and clustered genes preferentially expressed in fish previtellogenic oocytes. Gene. 2011;472:7\u201317.","journal-title":"Gene"},{"issue":"Suppl","key":"810_CR15","first-page":"202","volume":"32","author":"J-J Lareyre","year":"2008","unstructured":"Lareyre J-J, Ricordel M-J, Mah\u00e9 S, Goupil A-S, Vizziano D, Bobe J, et al. Two new TGF beta members are restricted to the gonad and differentially expressed during sex differentiation and gametogenesis in trout. Cybium. 2008;32(Suppl):202.","journal-title":"Cybium"},{"key":"810_CR16","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.ydbio.2006.10.001","volume":"301","author":"E Sawatari","year":"2007","unstructured":"Sawatari E, Shikina S, Takeuchi T, Yoshizaki G. A novel transforming growth factor-\u03b2 superfamily member expressed in gonadal somatic cells enhances primordial germ cell and spermatogonial proliferation in rainbow trout (Oncorhynchus mykiss). Dev Biol. 2007;301:266\u201375.","journal-title":"Dev Biol"},{"key":"810_CR17","doi-asserted-by":"publisher","first-page":"684352","DOI":"10.3389\/fcell.2021.684352","volume":"9","author":"C-w Hsu","year":"2021","unstructured":"Hsu C-w, Chung B-c. Evolution, expression, and function of gonadal somatic cell-derived factor. Front Cell Dev Biol. 2021;9:684352.","journal-title":"Front Cell Dev Biol"},{"key":"810_CR18","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.mce.2015.08.008","volume":"415","author":"H Kaneko","year":"2015","unstructured":"Kaneko H, Ijiri S, Kobayashi T, Izumi H, Kuramochi Y, Wang D-S, et al. Gonadal soma-derived factor (gsdf), a TGF-beta superfamily gene, induces testis differentiation in the teleost fish Oreochromis niloticus. Mol Cell Endocrinol. 2015;415:87\u201399.","journal-title":"Mol Cell Endocrinol"},{"key":"810_CR19","doi-asserted-by":"publisher","first-page":"17716","DOI":"10.1038\/s41598-018-35553-7","volume":"8","author":"Y Zhu","year":"2018","unstructured":"Zhu Y, Meng L, Xu W, Cui Z, Zhang N, Guo H, et al. The autosomal Gsdf gene plays a role in male gonad development in Chinese tongue sole (Cynoglossus semilaevis). Sci Rep. 2018;8:17716.","journal-title":"Sci Rep"},{"key":"810_CR20","doi-asserted-by":"crossref","unstructured":"Klopp C, Lasalle A, Di Landro S, Vizziano-Cantonnet D. RNA-Seq transcriptome data of undifferentiated and differentiated gonads of Siberian sturgeon. Data Brief. 2020;31:105741.","DOI":"10.1016\/j.dib.2020.105741"},{"key":"810_CR21","unstructured":"Benech-Correa G, Lasalle Gerla AE, Vizziano Cantonnet D. gsdf is the only major pro-male gene activated during the molecular sex differentiation period of Siberian sturgeon. 30th CECE & 9th ISFE Joint Conference of the European Society for Comparative Endocrinology and of the International Society for Fish Endocrinology; Faro, Portugal. 2022."},{"key":"810_CR22","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-3-319-61664-3_1","volume-title":"The Siberian sturgeon (Acipenser baerii, Brandt, 1869) volume 1 - Biology","author":"GI Ruban","year":"2018","unstructured":"Ruban GI. Geographical Distribution, ecological and biological characteristics of the Siberian sturgeon species. In: Williot P, Nonnotte G, Vizziano-Cantonnet D, Chebanov M, editors. The Siberian sturgeon (Acipenser baerii, Brandt, 1869) volume 1 - Biology. Cham: Springer; 2018. pp. 3\u201328."},{"key":"810_CR23","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1111\/raq.12027","volume":"6","author":"M Rzepkowska","year":"2013","unstructured":"Rzepkowska M, Ostaszewska T. Proliferating cell nuclear antigen and Vasa protein expression during gonadal development and sexual differentiation in cultured Siberian (Acipenser baerii Brandt, 1869) and Russian (Acipenser gueldenstaedtii Brandt & Ratzeburg, 1833) sturgeon. R Rev Aquacult. 2013;6:75\u201388.","journal-title":"R Rev Aquacult"},{"key":"810_CR24","doi-asserted-by":"publisher","first-page":"20200089","DOI":"10.1098\/rstb.2020.0089","volume":"376","author":"H Kuhl","year":"2021","unstructured":"Kuhl H, Guiguen Y, H\u00f6hne C, Kreuz E, Du K, Klopp C, et al. A 180 Myr-old female-specific genome region in sturgeon reveals the oldest known vertebrate sex determining system with undifferentiated sex chromosomes. Philos T R Soc B. 2021;376:20200089.","journal-title":"Philos T R Soc B"},{"key":"810_CR25","doi-asserted-by":"publisher","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","volume":"34","author":"S Chen","year":"2018","unstructured":"Chen S, Zhou Y, Chen Y, Gu J. Fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics. 2018;34:i884\u201390.","journal-title":"Bioinformatics"},{"key":"810_CR26","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li H, Durbin R. Fast and accurate short read alignment with Burrows\u2013Wheeler transform. Bioinformatics. 2009;25:1754\u201360.","journal-title":"Bioinformatics"},{"key":"810_CR27","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","volume":"25","author":"H Li","year":"2009","unstructured":"Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The sequence alignment\/map format and samtools. Bioinformatics. 2009;25:2078\u20139.","journal-title":"Bioinformatics"},{"key":"810_CR28","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3389\/fgene.2015.00002","volume":"6","author":"AF Palazzo","year":"2015","unstructured":"Palazzo AF, Lee ES. Non-coding RNA: what is functional and what is junk? Front Genet. 2015;6:2.","journal-title":"Front Genet"},{"key":"810_CR29","unstructured":"Alexa A, topGO. Enrichment Analysis for Gene Ontology. R package version. 2016;2(0)."},{"key":"810_CR30","unstructured":"Sokal RR, Rohlf FJ. Biometry: the principles and practice of statistics in biological research. In: WH Freeman editor. New York, USA; 1995."},{"key":"810_CR31","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.ygcen.2018.08.007","volume":"268","author":"D Vizziano-Cantonnet","year":"2018","unstructured":"Vizziano-Cantonnet D, Lasalle A, Di Landro S, Klopp C, Genthon C. De Novo transcriptome analysis to search for sex-differentiation genes in the Siberian sturgeon. Gen Comp Endocrinol. 2018;268:96\u2013109.","journal-title":"Gen Comp Endocrinol"},{"key":"810_CR32","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1111\/jai.14268","volume":"37","author":"A Lasalle","year":"2021","unstructured":"Lasalle A, Norbis W, Vizziano-Cantonnet D. Sex identification of morphologically\u2010undifferentiated Siberian sturgeon with statistical analysis of gene expression patterns. J Appl Ichthyol. 2021;37:835\u201346.","journal-title":"J Appl Ichthyol"},{"key":"810_CR33","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1002\/mrd.22589","volume":"83","author":"D Vizziano-Cantonnet","year":"2016","unstructured":"Vizziano-Cantonnet D, Di Landro S, Lasalle A, Mart\u00ednez A, Mazzoni TS, Quagio\u2010Grassiotto I. Identification of the molecular sex\u2010differentiation period in the Siberian sturgeon. Mol Reprod Dev. 2016;83:19\u201336.","journal-title":"Mol Reprod Dev"},{"key":"810_CR34","doi-asserted-by":"crossref","unstructured":"Fujimoto J, Hori M, Ichigo S, Morishita S, Tamaya T. Estrogen induces expression of c-fos and c-jun via activation of protein kinase C in an endometrial cancer cell line and fibroblasts derived from human uterine endometrium. Gynecol Endocrinol. 1996;10:109\u2009\u2013\u200918.","DOI":"10.3109\/09513599609097900"},{"key":"810_CR35","doi-asserted-by":"crossref","unstructured":"Webb DK, Moulton BC, Khan SA. Estrogen induces expression of c-jun and jun-b protooncogenes in specific rat uterine cells. Endocrinology. 1993;133:20\u2009\u2013\u20098.","DOI":"10.1210\/endo.133.1.8319568"},{"key":"810_CR36","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.reprotox.2014.10.010","volume":"50","author":"H-R Kim","year":"2014","unstructured":"Kim H-R, Kim YS, Yoon JA, Lyu SW, Shin H, Lim HJ, et al. Egr1 is rapidly and transiently induced by Estrogen and bisphenol A via activation of nuclear Estrogen receptor-dependent ERK1\/2 pathway in the uterus. Reprod Toxicol. 2014;50:60\u20137.","journal-title":"Reprod Toxicol"},{"key":"810_CR37","doi-asserted-by":"crossref","unstructured":"Punetha M, Kumar S, Paul A, Jose B, Bharati J, Sonwane A, et al. Deciphering the functional role of EGR1 in prostaglandin F2 alpha induced luteal regression applying CRISPR in corpus luteum of Buffalo. Biol Res. 2021;54:9.","DOI":"10.1186\/s40659-021-00333-7"},{"key":"810_CR38","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1210\/me.2002-0066","volume":"17","author":"DL Russell","year":"2003","unstructured":"Russell DL, Doyle KMH, Gonzales-Robayna I, Pipaon C, Richards JS. Egr-1 induction in rat granulosa cells by follicle-stimulating hormone and luteinizing hormone: combinatorial regulation by transcription factors Cyclic adenosine 3\u2032, 5\u2032-monophosphate regulatory element binding protein, serum response factor, sp1, and early growth response factor-1. Mol Endocrinol. 2003;17:520\u201333.","journal-title":"Mol Endocrinol"},{"key":"810_CR39","first-page":"163","volume":"1592","author":"M-H Bae","year":"2002","unstructured":"Bae M-H, Jeong C-H, Kim S-H, Bae M-K, Jeong J-W, Ahn M-Y, et al. Regulation of Egr-1 by association with the proteasome component C8. BBA-Mol Cell Res. 2002;1592:163\u20137.","journal-title":"BBA-Mol Cell Res"},{"key":"810_CR40","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/S0079-6603(08)60815-6","volume":"50","author":"A Gashler","year":"1995","unstructured":"Gashler A, Sukhatme VP. Early growth response protein 1 (Egr-1): prototype of a zinc-finger family of transcription factors. Prog Nucleic Acid Res. 1995;50:191\u2013224.","journal-title":"Prog Nucleic Acid Res"},{"key":"810_CR41","first-page":"863","volume":"18","author":"J Liu","year":"2001","unstructured":"Liu J, Grogan L, Nau MM, Allegra CJ, Chu E, Wright JJ. Physical interaction between p53 and primary response gene Egr-1. Int J Oncol. 2001;18:863\u201370.","journal-title":"Int J Oncol"},{"key":"810_CR42","doi-asserted-by":"publisher","first-page":"101913","DOI":"10.1016\/j.aqrep.2024.101913","volume":"34","author":"J Zhang","year":"2024","unstructured":"Zhang J, Yang J, Ma Z, Pu H, Zhang T, Guo J, et al. Molecular and cellular regulation on sexual fate and gonadal development in hermaphrodite Yellowfin seabream Acanthopagrus latus. Aquaculture Rep. 2024;34:101913.","journal-title":"Aquaculture Rep"},{"key":"810_CR43","doi-asserted-by":"publisher","DOI":"10.1101\/2023.12.20.572697","author":"D Rocks","year":"2023","unstructured":"Rocks D, Purisic E, Gallo EF, Greally JM, Suzuki M, Kundakovic M. Egr1 is a sex-specific regulator of neuronal chromatin, synaptic plasticity, and behaviour. BioRxiv. 2023. https:\/\/doi.org\/10.1101\/2023.12.20.572697.","journal-title":"BioRxiv"},{"key":"810_CR44","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1210\/me.2004-0103","volume":"18","author":"Y Arao","year":"2004","unstructured":"Arao Y, Kikuchi A, Kishida M, Yonekura M, Inoue A, Yasuda S, et al. Stability of A\u2009+\u2009U-rich element binding factor 1 (AUF1)-binding messenger ribonucleic acid correlates with the subcellular relocalization of AUF1 in the rat uterus upon Estrogen treatment. Mol Endocrinol. 2004;18:2255\u201367.","journal-title":"Mol Endocrinol"},{"key":"810_CR45","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1210\/endo-100-6-1496","volume":"100","author":"A De Lean","year":"1977","unstructured":"De Lean A, Ferland L, Drouin J, Kelly PA, Labrie F. Modulation of pituitary Thyrotropin releasing hormone receptor levels by estrogens and thyroid hormones. Endocrinology. 1977;100:1496\u2013504.","journal-title":"Endocrinology"},{"key":"810_CR46","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1210\/endo-105-1-171","volume":"105","author":"MC Gershengorn","year":"1979","unstructured":"Gershengorn MC, Marcus-Samuels BE, Geras E. Estrogens increase the number of thyrotropin-releasing hormone receptors on mammotropic cells in culture. Endocrinology. 1979;105:171\u20136.","journal-title":"Endocrinology"},{"key":"810_CR47","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1210\/endo.134.1.8275956","volume":"134","author":"N Kimura","year":"1994","unstructured":"Kimura N, Arai K, Sahara Y, Suzuki H, Kimura N. Estradiol transcriptionally and posttranscriptionally up-regulates thyrotropin-releasing hormone receptor messenger ribonucleic acid in rat pituitary cells. Endocrinology. 1994;134:432\u201340.","journal-title":"Endocrinology"},{"key":"810_CR48","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.pharmthera.2012.09.001","volume":"137","author":"S Healy","year":"2013","unstructured":"Healy S, Khan P, Davie JR. Immediate early response genes and cell transformation. Pharmacol Therapeut. 2013;137:64\u201377.","journal-title":"Pharmacol Therapeut"},{"key":"810_CR49","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1042\/BST20110636","volume":"40","author":"A O\u2019Donnell","year":"2012","unstructured":"O\u2019Donnell A, Odrowaz Z, Sharrocks AD. Immediate-early gene activation by the MAPK pathways: what do and don\u2019t we know? Biochem Soc T. 2012;40:58\u201366.","journal-title":"Biochem Soc T"},{"key":"810_CR50","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1111\/j.1749-6632.2009.03705.x","volume":"1155","author":"SE Bulun","year":"2009","unstructured":"Bulun SE, Lin Z, Zhao H, Lu M, Amin S, Reierstad S, et al. Regulation of aromatase expression in breast cancer tissue. Ann NY Acad Sci. 2009;1155:121\u201331.","journal-title":"Ann NY Acad Sci"},{"issue":"5","key":"810_CR51","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1210\/me.2010-0368","volume":"25","author":"D Chen","year":"2011","unstructured":"Chen D, Reierstad S, Fang F, Bulun SE. JunD and JunB integrate prostaglandin E2 activation of breast cancer-associated proximal aromatase promoters. Mol Endocrinol. 2011;25(5):767\u201375.","journal-title":"Mol Endocrinol"},{"key":"810_CR52","first-page":"129","volume":"1072","author":"P Angel","year":"1991","unstructured":"Angel P, Karin M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. BBA-Rev Cancer. 1991;1072:129\u201357.","journal-title":"BBA-Rev Cancer"},{"key":"810_CR53","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/0303-7207(89)90149-4","volume":"64","author":"B van der Burg","year":"1989","unstructured":"van der Burg B, van Selm-Miltenburg AJP, de Laat SW, van Zoelen EJJ. Direct effects of Estrogen on c-fos and c-myc protooncogene expression and cellular proliferation in human breast cancer cells. Mol Cell Endocrinol. 1989;64:223\u20138.","journal-title":"Mol Cell Endocrinol"},{"issue":"Suppl2","key":"810_CR54","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1136\/ard.61.suppl_2.ii40","volume":"61","author":"EF Wagner","year":"2002","unstructured":"Wagner EF. Functions of AP1 (Fos\/Jun) in bone development. Ann Rheum Dis. 2002;61(Suppl2):40\u20132.","journal-title":"Ann Rheum Dis"},{"key":"810_CR55","doi-asserted-by":"publisher","first-page":"e1006281","DOI":"10.1371\/journal.pgen.1006281","volume":"12","author":"JD Klein","year":"2016","unstructured":"Klein JD, Qu C, Yang X, Fan Y, Tang C, Peng JC. c-Fos repression by Piwi regulates Drosophila ovarian germline formation and tissue morphogenesis. PLoS Genet. 2016;12:e1006281.","journal-title":"PLoS Genet"},{"key":"810_CR56","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/s10616-020-00447-y","volume":"73","author":"M Zhang","year":"2021","unstructured":"Zhang M, Xu P, Sun X, Zhang C, Shi X, Li J, et al. JUN promotes chicken female differentiation by inhibiting Smad2. Cytotechnology. 2021;73:101\u201313.","journal-title":"Cytotechnology"},{"key":"810_CR57","doi-asserted-by":"publisher","first-page":"2230","DOI":"10.1073\/pnas.0812880106","volume":"106","author":"S-K Hong","year":"2009","unstructured":"Hong S-K, Dawid IB. FGF-dependent left\u2013right asymmetry patterning in zebrafish is mediated by Ier2 and Fibp1. Proc Natl Acad Sci USA. 2009;106:2230\u20135.","journal-title":"Proc Natl Acad Sci USA"},{"key":"810_CR58","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1387\/ijdb.113288sh","volume":"55","author":"S-K Hong","year":"2011","unstructured":"Hong S-K, Tanegashima K, Dawid IB. XIer2 is required for convergent extension movements during xenopus development. Int J Dev Biol. 2011;55:917.","journal-title":"Int J Dev Biol"},{"key":"810_CR59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ydbio.2015.04.023","volume":"404","author":"J Irizarry","year":"2015","unstructured":"Irizarry J, Stathopoulos A. FGF signaling supports Drosophila fertility by regulating development of ovarian muscle tissues. Dev Biol. 2015;404:1\u201313.","journal-title":"Dev Biol"},{"key":"810_CR60","unstructured":"Jayasimha C. Expression and hormonal regulation of transcriptional regulatory genes modulated by luteinizing hormone in Buffalo ovarian cells identified using comparative genomics. 2011. (Doctoral dissertation, NDRI)."},{"key":"810_CR61","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.ccr.2007.01.013","volume":"11","author":"M Shipitsin","year":"2007","unstructured":"Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, et al. Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007;11:259\u201373.","journal-title":"Cancer Cell"},{"key":"810_CR62","doi-asserted-by":"publisher","first-page":"614","DOI":"10.4149\/neo_2020_190818N781","volume":"67","author":"X Xu","year":"2020","unstructured":"Xu X, Zhou W, Chen Y, Wu K, Wang H, Zhang J, et al. Immediate early response protein 2 promotes the migration and invasion of hepatocellular carcinoma cells via regulating the activity of Rho GTPases. Neoplasma. 2020;67:614\u201322.","journal-title":"Neoplasma"},{"key":"810_CR63","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.ygcen.2018.04.023","volume":"265","author":"A Tovo-Neto","year":"2018","unstructured":"Tovo-Neto A, da Silva Rodrigues M, Habibi HR, N\u00f3brega RH. Thyroid hormone actions on male reproductive system of teleost fish. Gen Comp Endocrinol. 2018;265:230\u20136.","journal-title":"Gen Comp Endocrinol"},{"key":"810_CR64","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1002\/etc.5620210318","volume":"21","author":"WL Goleman","year":"2002","unstructured":"Goleman WL, Carr JA, Anderson TA. Environmentally relevant concentrations of ammonium perchlorate inhibit thyroid function and alter sex ratios in developing Xenopus laevis. Environ Toxicol Chem. 2002;21:590\u20137.","journal-title":"Environ Toxicol Chem"},{"key":"810_CR65","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1093\/icb\/37.2.185","volume":"37","author":"TB Hayes","year":"1997","unstructured":"Hayes TB. Steroids as potential modulators of thyroid hormone activity in Anuran metamorphosis. Am Zool. 1997;37:185\u201394.","journal-title":"Am Zool"},{"key":"810_CR66","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.ygcen.2016.05.028","volume":"235","author":"P Sharma","year":"2016","unstructured":"Sharma P, Tang S, Mayer GD, Pati\u00f1o R. Effects of thyroid endocrine manipulation on sex-related gene expression and population sex ratios in zebrafish. Gen Comp Endocrinol. 2016;235:38\u201347.","journal-title":"Gen Comp Endocrinol"},{"key":"810_CR67","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s00018-023-04913-6","volume":"80","author":"DC Casta\u00f1eda-Cort\u00e9s","year":"2023","unstructured":"Casta\u00f1eda-Cort\u00e9s DC, Rosa IF, Boan AF, Marrone D, Pagliaro N, Oliveira MA, et al. Thyroid axis participates in high-temperature-induced male sex reversal through its activation by the stress response. Cell Mol Life Sci. 2023;80:253.","journal-title":"Cell Mol Life Sci"},{"key":"810_CR68","doi-asserted-by":"crossref","unstructured":"Feng K, Su J, Wu Z, Su S, Yao W. Molecular cloning and expression analysis of Thyrotropin-Releasing Hormone, and its possible role in gonadal differentiation in rice field eel Monopterus albus. Animals. 2022;12:1691.","DOI":"10.3390\/ani12131691"},{"key":"810_CR69","doi-asserted-by":"crossref","unstructured":"Klopp C, Cabau C, Greif G, Lasalle A, Di Landro S, Vizziano-Cantonnet DJD. Siberian sturgeon multi-tissue reference transcriptome database. Database. 2020;2020.","DOI":"10.1093\/database\/baaa082"},{"key":"810_CR70","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1093\/molehr\/5.5.402","volume":"5","author":"MT Itoh","year":"1999","unstructured":"Itoh MT, Ishizuka B, Kuribayashi Y, Amemiya A, Sumi Y. Melatonin, its precursors, and synthesizing enzyme activities in the human ovary. Mol Hum Reprod. 1999;5:402\u20138.","journal-title":"Mol Hum Reprod"},{"key":"810_CR71","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/0039-128X(95)00197-X","volume":"61","author":"M Tijmes","year":"1996","unstructured":"Tijmes M, Pedraza R, Valladares L. Melatonin in the rat testis: evidence for local synthesis. Steroids. 1996;61:65\u20138.","journal-title":"Steroids"},{"key":"810_CR72","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.anireprosci.2012.11.004","volume":"136","author":"AK Singh","year":"2013","unstructured":"Singh AK, Singh R. In vivo response of melatonin, gonadal activity and biochemical changes during CYP19 inhibited sex reversal in common carp Cyprinus Carpio (L). Anim Reprod Sci. 2013;136:317\u201325.","journal-title":"Anim Reprod Sci"},{"key":"810_CR73","doi-asserted-by":"crossref","unstructured":"Piferrer F. Epigenetics of sex determination and differentiation in fish. In: Han-Ping Wang, Francesc Piferrer, Song-Lin Chen, Zhi-Gang, Shen, editors. Sex control in aquaculture. 2018:65\u201383.","DOI":"10.1002\/9781119127291.ch3"},{"key":"810_CR74","doi-asserted-by":"publisher","first-page":"522","DOI":"10.3389\/fgene.2019.00522","volume":"10","author":"J Liu","year":"2019","unstructured":"Liu J, Liu X, Jin C, Du X, He Y, Zhang Q. Transcriptome profiling insights the feature of sex reversal induced by high temperature in tongue sole Cynoglossus semilaevis. Front Genet. 2019;10:522.","journal-title":"Front Genet"},{"key":"810_CR75","doi-asserted-by":"crossref","unstructured":"Zhang Y, Xu F, Li H, Chen S. Differential methylation reveals pathways associated with sex differentiation in Chinese tongue sole (Cynoglossus semilaevis). Aquaculture and Fisheries; 2024.","DOI":"10.1016\/j.aaf.2024.12.002"},{"key":"810_CR76","first-page":"97","volume":"32","author":"J Liu","year":"2008","unstructured":"Liu J, Mahe S, Guiguen Y. Expression of the T-box transcription factor, T-box 1 (tbx1), during rainbow trout (Oncorhynchus mykiss) testicular differentiation. Cybium. 2008;32:97.","journal-title":"Cybium"},{"key":"810_CR77","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1002\/mrd.21279","volume":"78","author":"A Yano","year":"2011","unstructured":"Yano A, Nicol B, Guerin A, Guiguen Y. The duplicated rainbow trout (Oncorhynchus mykiss) T-box transcription factors 1, tbx1a and tbx1b, are up\u2010regulated during testicular development. Mol Reprod Dev. 2011;78:172\u201380.","journal-title":"Mol Reprod Dev"},{"key":"810_CR78","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1016\/j.ygeno.2018.09.007","volume":"111","author":"Q Hu","year":"2019","unstructured":"Hu Q, Meng Y, Wang D, Tian H, Xiao H. Characterization and function of the T-box 1 gene in Chinese giant salamander Andrias Davidianus. Genomics. 2019;111:1351\u20139.","journal-title":"Genomics"},{"key":"810_CR79","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1007\/s10528-024-10815-4","volume":"63","author":"G Wan","year":"2025","unstructured":"Wan G, Zhang H, Wang P, Qin Q, Zhou X, Xiong G, et al. Gonadal transcriptome analysis reveals that SOX17 and CYP26A1 are involved in sex differentiation in the Chinese soft-shelled turtle (Pelodiscus sinensis). Biochem Genet. 2025;63:2190\u2013210.","journal-title":"Biochem Genet"},{"key":"810_CR80","first-page":"101200","volume":"50","author":"S Yang","year":"2024","unstructured":"Yang S, Tang X, Yan F, Yang H, Xu L, Jian Z, et al. A time-course transcriptome analysis revealing the potential molecular mechanism of early gonadal differentiation in the Chinese giant salamander. Comp Biochem Phys D. 2024;50:101200.","journal-title":"Comp Biochem Phys D"},{"key":"810_CR81","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/nrm2125","volume":"8","author":"A Page-McCaw","year":"2007","unstructured":"Page-McCaw A, Ewald AJ, Werb Z. Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Bio. 2007;8:221\u201333.","journal-title":"Nat Rev Mol Cell Bio"},{"key":"810_CR82","doi-asserted-by":"publisher","first-page":"114137","DOI":"10.1016\/j.ygcen.2022.114137","volume":"330","author":"JJ Carver","year":"2023","unstructured":"Carver JJ, Zhu Y. Metzincin metalloproteases in PGC migration and gonadal sex conversion. Gen Comp Endocrinol. 2023;330:114137.","journal-title":"Gen Comp Endocrinol"},{"key":"810_CR83","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1111\/j.2047-2927.2013.00109.x","volume":"1","author":"A D\u00edez-Torre","year":"2013","unstructured":"D\u00edez-Torre A, D\u00edaz\u2010N\u00fa\u00f1ez M, Eguiz\u00e1bal C, Silv\u00e1n U, Ar\u00e9chaga J. Evidence for a role of matrix metalloproteinases and their inhibitors in primordial germ cell migration. Andrology. 2013;1:779\u201386.","journal-title":"Andrology"},{"key":"810_CR84","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1007\/s00441-020-03288-5","volume":"383","author":"TS Mazzoni","year":"2021","unstructured":"Mazzoni TS, Quagio-Grassiotto I. Presence of the matrix metalloproteinases during the migration of the primordial germ cells in zebrafish gonadal ridge. Cell Tissue Res. 2021;383:707\u201322.","journal-title":"Cell Tissue Res"},{"key":"810_CR85","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3390\/cells7050034","volume":"7","author":"TS Mazzoni","year":"2018","unstructured":"Mazzoni TS, Lo Nostro FL, Antoneli FN, Quagio-Grassiotto I. Action of the metalloproteinases in gonadal remodeling during sex reversal in the sequential hermaphroditism of the teleostei fish Synbranchus marmoratus (Synbranchiformes: Synbranchidae). Cells. 2018;7:34.","journal-title":"Cells"},{"key":"810_CR86","doi-asserted-by":"publisher","first-page":"34281","DOI":"10.1038\/srep34281","volume":"6","author":"MC Adolfi","year":"2016","unstructured":"Adolfi MC, Herpin A, Regensburger M, Sacquegno J, Waxman JS, Schartl M. Retinoic acid and meiosis induction in adult versus embryonic gonads of Medaka. Sci Rep. 2016;6:34281.","journal-title":"Sci Rep"},{"key":"810_CR87","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.3390\/nu14061293","volume":"14","author":"MC Schleif","year":"2022","unstructured":"Schleif MC, Havel SL, Griswold MD. Function of retinoic acid in development of male and female gametes. Nutrients. 2022;14:1293.","journal-title":"Nutrients"}],"container-title":["Biology of Sex Differences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13293-025-00810-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13293-025-00810-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13293-025-00810-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:03:09Z","timestamp":1770040989000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13293-025-00810-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,2]]},"references-count":87,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["810"],"URL":"https:\/\/doi.org\/10.1186\/s13293-025-00810-8","relation":{},"ISSN":["2042-6410"],"issn-type":[{"value":"2042-6410","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,2]]},"assertion":[{"value":"9 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experiments and animal maintenance were conducted in accordance with the regulations of the Comisi\u00f3n Honoraria de Experimentaci\u00f3n Animal (CHEA), which regulates all protocols involving animal experimentation, under protocol No. 1516 (exp. 240012-000023-22).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17"}}