{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:47:53Z","timestamp":1784202473395,"version":"3.55.0"},"reference-count":63,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Nature Science Foundation of China","award":["31972997"],"award-info":[{"award-number":["31972997"]}]},{"name":"National Nature Science Foundation of China","award":["2022BBA0049"],"award-info":[{"award-number":["2022BBA0049"]}]},{"name":"National Nature Science Foundation of China","award":["CARS-38"],"award-info":[{"award-number":["CARS-38"]}]},{"name":"Provincial Key R&amp;D Program of Hubei","award":["31972997"],"award-info":[{"award-number":["31972997"]}]},{"name":"Provincial Key R&amp;D Program of Hubei","award":["2022BBA0049"],"award-info":[{"award-number":["2022BBA0049"]}]},{"name":"Provincial Key R&amp;D Program of Hubei","award":["CARS-38"],"award-info":[{"award-number":["CARS-38"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["31972997"],"award-info":[{"award-number":["31972997"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["2022BBA0049"],"award-info":[{"award-number":["2022BBA0049"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["CARS-38"],"award-info":[{"award-number":["CARS-38"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Animal reproduction performance is crucial in husbandry. Immunocastrated animals serve as an ideal animal model for studying testicular function. During androgen suppression, the testis undergoes dramatic developmental and structural changes, including the inhibition of hormone secretion and spermatogenesis. Methods: To characterize this process, we investigated the effects of castration using a recombinant B2L and KISS1 DNA vaccine, and then identified functional genes in the testes of Yiling goats using RNA-seq and WGS. The experimental animals were divided into three groups: the PVAX-asd group (control), PBK-asd-immunized group, and surgically castrated group. Results: The results demonstrated that the administration of the recombinant PBK-asd vaccine in goats elicited a significant antibody response, and reduced serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH), resulting in smaller scrotal circumferences and decreased sexual desire compared to the control group. In addition, RNA transcriptome sequencing (RNA-seq) analysis of the testes revealed that the biological processes after immunocastration mainly focused on the regulation of cell matrix adhesion, histone acetylation, negative regulation of developmental processes, apoptosis, and activation of the complement system and the thrombin cascade reaction system. Then, we integrated the whole-genome sequencing and testis transcriptome, and identified several candidate genes (FGF9, FST, KIT, TH, TCP1, PLEKHA1, TMEM119, ESR1, TIPARP, LEP) that influence steroidogenesis secretion and spermatogenesis. Conclusions: Multiple pathways and polygenic co-expression participate in the response to castration vaccines, altering hormone secretion and spermatogenesis. Taken together, our atlas of the immunocastration goat testis provides multiple insights into the developmental changes and key factors accompanying androgen suppression, and thus may contribute to understanding the genetic mechanism of testis function. Joint analysis of whole genome sequencing and RNA-seq enables reliable screening of candidate genes, benefiting future genome-assisted breeding of goats.<\/jats:p>","DOI":"10.3390\/cells13010006","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T03:51:45Z","timestamp":1703044305000},"page":"6","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Multiple-Pathway Synergy Alters Steroidogenesis and Spermatogenesis in Response to an Immunocastration Vaccine in Goat"],"prefix":"10.3390","volume":"13","author":[{"given":"Yi","family":"Ding","sequence":"first","affiliation":[{"name":"Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Smart Farming for Agricultural Animals, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Laboratory of Small Ruminant Genetics, Breeding and Reproduction, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunping","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Smart Farming for Agricultural Animals, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Laboratory of Small Ruminant Genetics, Breeding and Reproduction, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1380-4692","authenticated-orcid":false,"given":"Ling","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Smart Farming for Agricultural Animals, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Laboratory of Small Ruminant Genetics, Breeding and Reproduction, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyu","family":"Sha","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Smart Farming for Agricultural Animals, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Laboratory of Small Ruminant Genetics, Breeding and Reproduction, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Smart Farming for Agricultural Animals, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Laboratory of Small Ruminant Genetics, Breeding and Reproduction, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Sohail","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Smart Farming for Agricultural Animals, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Laboratory of Small Ruminant Genetics, Breeding and Reproduction, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3688-5958","authenticated-orcid":false,"given":"Guiqiong","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Key Laboratory of Smart Farming for Agricultural Animals, Huazhong Agricultural University, Wuhan 430070, China"},{"name":"Laboratory of Small Ruminant Genetics, Breeding and Reproduction, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, 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J. Anim. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/nature01019","article-title":"Evolution, consequences and future of plant and animal domestication","volume":"418","author":"Diamond","year":"2002","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6139","DOI":"10.1073\/pnas.1323964111","article-title":"Current perspectives and the future of domestication studies","volume":"111","author":"Larson","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.metabol.2017.11.018","article-title":"The hypothalamus-pituitary-gonad axis: Tales of mice and men","volume":"86","author":"Kaprara","year":"2018","journal-title":"Metabolism"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1080\/00480169.2005.36560","article-title":"The welfare significance of the castration of cattle: A review","volume":"53","author":"Stafford","year":"2005","journal-title":"N. Z. Veter. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1017\/S1751731112000146","article-title":"Meta-analysis of the effect of immunocastration on production performance, reproductive organs and boar taint compounds in pigs","volume":"6","author":"Batorek","year":"2012","journal-title":"Animal"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.theriogenology.2014.10.029","article-title":"Effect of immunization against GnRH on hypothalamic and testicular function in rams","volume":"83","author":"Han","year":"2015","journal-title":"Theriogenology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/biolre\/iox176","article-title":"Effects of active immunization with newly modified GnRH peptides on spermatogenesis and production performance of Holstein bulls","volume":"99","author":"Xu","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.theriogenology.2018.01.013","article-title":"Effect of active immunization using a novel GnRH vaccine on reproductive function in rats","volume":"111","author":"Yao","year":"2018","journal-title":"Theriogenology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1210\/en.2005-1397","article-title":"Effects of single or repeated intravenous administration of kisspeptin upon dynamic LH secretion in conscious male rats","volume":"147","author":"Tovar","year":"2006","journal-title":"Endocrinology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.lfs.2010.11.019","article-title":"Intraperitoneal kisspeptin-10 administration induces dose-dependent degenerative changes in maturing rat testes","volume":"88","author":"Ramzan","year":"2011","journal-title":"Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"17391","DOI":"10.1523\/JNEUROSCI.2438-12.2012","article-title":"Genetic mechanisms mediating kisspeptin regulation of GnRH gene expression","volume":"32","author":"Novaira","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1007\/s12035-015-9269-0","article-title":"Kisspeptin induces dynamic chromatin modifications to control GnRH gene expression","volume":"53","author":"Novaira","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1210\/me.2012-1405","article-title":"Kisspeptin regulates gonadotropin genes via immediate early gene induction in pituitary gonadotropes","volume":"27","author":"Witham","year":"2013","journal-title":"Mol. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"R131","DOI":"10.1530\/JME-17-0308","article-title":"Molecular regulation of follicle-stimulating hormone synthesis, secretion and action","volume":"60","author":"Das","year":"2018","journal-title":"J. Mol. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1007\/s00705-016-3178-z","article-title":"Functional characterization of recombinant major envelope protein (rB2L) of orf virus","volume":"162","author":"Yogisharadhya","year":"2017","journal-title":"Arch. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zhao, K., Song, D., Du, L., Wang, X., Gao, F., Lu, H., and Guan, J. (2022). Evaluation of the Immune Response Afforded by Combined Immunization with Orf Virus DNA and Subunit Vaccine in Mice. Vaccines, 10.","DOI":"10.3390\/vaccines10091499"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e13307","DOI":"10.1111\/asj.13307","article-title":"Effects of immunocastration performed at two live weights on the growth physiology, temperament and testicular development of feral beef bulls","volume":"91","author":"Noya","year":"2020","journal-title":"Anim. Sci. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/s41597-022-01917-y","article-title":"A transcriptome dataset for gonadectomy-induced changes in rat spinal cord","volume":"9","author":"Miller","year":"2022","journal-title":"Sci. Data"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1038\/s41467-023-36681-z","article-title":"Intra-pituitary follicle-stimulating hormone signaling regulates hepatic lipid metabolism in mice","volume":"14","author":"Qiao","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16262","DOI":"10.1038\/s41598-019-52744-y","article-title":"Recombinant B2L and kisspeptin-54 DNA vaccine induces immunity against orf virus and inhibits spermatogenesis in rats","volume":"9","author":"Wassie","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.vetimm.2004.03.011","article-title":"Efficacy of an anti-fertility vaccine based on mammalian gonadotrophin releasing hormone (GnRH-I)\u2014A histological comparison in male animals","volume":"101","author":"Ferro","year":"2004","journal-title":"Veter. Immunol. Immunopathol."},{"key":"ref_23","unstructured":"(2018, June 12). Babraham Bioinformatics\u2014FastQC A Quality Control Tool for High Throughput Sequence Data. Available online: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/1477-7827-8-96","article-title":"ReCGiP, a database of reproduction candidate genes in pigs based on bibliomics","volume":"8","author":"Yang","year":"2010","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.mce.2006.04.030","article-title":"Kisspepeptin-GPR54 signaling in the neuroendocrine reproductive axis","volume":"254\u2013255","author":"Gottsch","year":"2006","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6609","DOI":"10.1210\/jc.2005-1468","article-title":"Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males","volume":"90","author":"Dhillo","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10972","DOI":"10.1073\/pnas.1834399100","article-title":"Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54","volume":"100","author":"Genin","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4565","DOI":"10.1210\/en.2004-0413","article-title":"Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing activity of KiSS-1 peptide","volume":"145","author":"Navarro","year":"2004","journal-title":"Endocrinology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1016\/j.vaccine.2006.01.041","article-title":"Evaluation of two GnRH-I based vaccine formulations on the testes function of entire Suffolk cross ram lambs","volume":"24","author":"Earl","year":"2006","journal-title":"Vaccine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"485","DOI":"10.4103\/1008-682X.156856","article-title":"Active immunization with GnRH-tandem-dimer peptide in young male rats reduces serum reproductive hormone concentrations, testicular development and spermatogenesis","volume":"18","author":"Zeng","year":"2016","journal-title":"Asian J. Androl."},{"key":"ref_33","first-page":"54","article-title":"Immuno-castration by immunization with GnRH in Black Bengal bucks (Capra hircus)","volume":"9","author":"Mandal","year":"2019","journal-title":"Explor. Anim. Med. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.vaccine.2014.12.054","article-title":"KISS1 can be used as a novel target for developing a DNA immunocastration vaccine in ram lambs","volume":"33","author":"Han","year":"2015","journal-title":"Vaccine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4630","DOI":"10.1016\/j.vaccine.2017.09.001","article-title":"Kisspeptin recombinant oral vaccine: A master gene vaccine inhibiting the reproductive physiology and behavior of ram lambs","volume":"37","author":"Tesema","year":"2019","journal-title":"Vaccine"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1017\/S175173111000011X","article-title":"Immunocastration reduces aggressive and sexual behaviour in male pigs","volume":"4","author":"Rydhmer","year":"2010","journal-title":"Animal"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0079-6123(08)81005-9","article-title":"Physiological roles of the kisspeptin\/GPR54 system in the neuroendocrine control of reproduction","volume":"181","author":"Pineda","year":"2010","journal-title":"Prog. Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/978-1-4614-6199-9_12","article-title":"Kisspeptin and puberty in mammals","volume":"784","author":"Terasawa","year":"2013","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1093\/humupd\/dmn058","article-title":"The role of kisspeptin in the control of gonadotrophin secretion","volume":"15","author":"Roseweir","year":"2009","journal-title":"Hum. Reprod. Updat."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1262\/jrd.2018-110","article-title":"The roles of kisspeptin in the mechanism underlying reproductive functions in mammals","volume":"64","author":"Uenoyama","year":"2018","journal-title":"J. Reprod. Dev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.theriogenology.2018.03.013","article-title":"Immunocastration of goats using anti-gonadotrophin releasing hormone vaccine","volume":"114","author":"Lents","year":"2018","journal-title":"Theriogenology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.smallrumres.2018.11.016","article-title":"Influence of immunocastration vaccine administration interval on serum androgen concentrations and testis activity in ram lambs","volume":"170","author":"Needham","year":"2019","journal-title":"Small Rumin. Res."},{"key":"ref_43","first-page":"523","article-title":"Histone Acetylation and Mammalian Reproduction","volume":"39","author":"Yang","year":"2017","journal-title":"Chin. J. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4077","DOI":"10.1242\/jcs.00739","article-title":"Apoptosis-the p53 network","volume":"116","author":"Haupt","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"172","DOI":"10.2164\/jandrol.107.003848","article-title":"In Vivo Application of Histone Deacetylase Inhibitor Trichostatin\u2014A Impairs Murine Male Meiosis","volume":"29","author":"Fenic","year":"2008","journal-title":"J. Androl."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3389\/fphys.2017.00188","article-title":"Molecular and Cellular Mechanisms of Apoptosis during Dissociated Spermatogenesis","volume":"8","author":"Liu","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s00441-019-03150-3","article-title":"The cell\u2013cell junctions of mammalian testes\u2014A summary","volume":"379","author":"Domke","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s00441-018-2968-x","article-title":"The cell\u2013cell junctions of mammalian testes: II. The lamellar smooth muscle monolayer cells of the peritubular wall are laterally connected by vertical adherens junctions\u2014A novel architectonic cell\u2013cell junction system","volume":"375","author":"Domke","year":"2019","journal-title":"Cell Tissue Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s00441-019-03116-5","article-title":"The cell\u2013cell junctions of mammalian testes. III. Absence of an endothelial cell layer covering the peritubular wall of the seminiferous tubules\u2014An immunocytochemical correction of a 50-year-old error in the literature","volume":"379","author":"Franke","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.reprotox.2017.02.007","article-title":"Male reproductive toxicity of CrVI: In-utero exposure to CrVI at the critical window of testis differentiation represses the expression of Sertoli cell tight junction proteins and hormone receptors in adult F1 progeny rats","volume":"69","author":"Kumar","year":"2017","journal-title":"Reprod. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Bo, D., Jiang, X., Liu, G., Xu, F., Hu, R., Wassie, T., Chong, Y., Ahmed, S., Liu, C., and Girmay, S. (2020). Multipathway synergy promotes testicular transition from growth to spermatogenesis in early-puberty goats. BMC Genom., 21.","DOI":"10.1186\/s12864-020-6767-x"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1124\/pr.110.002790","article-title":"The blood-testis barrier and its implications for male contraception","volume":"64","author":"Cheng","year":"2011","journal-title":"Pharmacol. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1095\/biolreprod67.1.70","article-title":"Apoptosis, onset and maintenance of spermatogenesis: Evidence for the involvement of Kit in Kit-haplodeficient mice","volume":"67","author":"Guerif","year":"2002","journal-title":"Biol. Reprod."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1210\/me.2003-0364","article-title":"Overexpression of follistatin-like 3 in gonads causes defects in gonadal development and function in transgenic mice","volume":"18","author":"Xia","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Mizuhashi, K., Chaya, T., Kanamoto, T., Omori, Y., and Furukawa, T. (2015). Obif, a transmembrane protein, is required for bone mineralization and spermatogenesis in mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133704"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"36875","DOI":"10.1074\/jbc.M110.188888","article-title":"The chaperonin containing TCP1 complex (CCT\/TRiC) is involved in mediating sperm-oocyte interaction","volume":"286","author":"Dun","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1093\/biolre\/ioac088","article-title":"ESR1 mediates estrogen-induced feminization of genetic male Chinese soft-shelled turtle","volume":"107","author":"Li","year":"2022","journal-title":"Biol. Reprod."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1210\/en.2014-1852","article-title":"Estrogen receptor 1 (ESR1; ER\u03b1), not ESR2 (ER\u03b2), modulates estrogen-induced sex reversal in the American alligator, a species with temperature-dependent sex determination","volume":"156","author":"Kohno","year":"2015","journal-title":"Endocrinology"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Riis, M.L., and J\u00f8rgensen, A. (2022). Deciphering sex-specific differentiation of human fetal gonads: Insight from experimental models. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.902082"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Kourtidis, A., Dighera, B., Risner, A., Hackemack, R., and Nikolaidis, N. (2022). Origin and evolution of the multifaceted adherens junction component plekha7. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.856975"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Kamata, T., Yang, C.-S., Melhuish, T.A., Frierson, H.F., Wotton, D., and Paschal, B.M. (2021). Post-transcriptional regulation of PARP7 protein stability is controlled by androgen signaling. Cells, 10.","DOI":"10.3390\/cells10020363"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/S0306-4522(98)00341-8","article-title":"Gonadectomy in adult life increases tyrosine hydroxylase immunoreactivity in the prefrontal cortex and decreases open field activity in male rats","volume":"89","author":"Adler","year":"1999","journal-title":"Neuroscience"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"367","DOI":"10.3389\/fendo.2017.00367","article-title":"Leptin regulation of gonadotrope gonadotropin-releasing hormone receptors as a metabolic checkpoint and gateway to reproductive competence","volume":"8","author":"Odle","year":"2018","journal-title":"Front. Endocrinol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/1\/6\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:41:50Z","timestamp":1760132510000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/1\/6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,20]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["cells13010006"],"URL":"https:\/\/doi.org\/10.3390\/cells13010006","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,20]]}}}