{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:44:04Z","timestamp":1759970644872,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["32090022","31972285"],"award-info":[{"award-number":["32090022","31972285"]}]},{"name":"Xinjiang Tian-Chi Talents Introduction Program","award":["32090022","31972285"],"award-info":[{"award-number":["32090022","31972285"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Commonly in seasonal breeding animals, testicular development is inhibited prior to Sertoli cell maturation when environmental conditions become unfavorable, with recovery occurring once conditions improve. However, the precise molecular mechanisms governing this process remain unclear. We investigated the role of androgen receptor (AR) in the seasonal regulation of testicular development in a wild population of Rattus norvegicus caraco, a subspecies of brown rats in Northeast China residing in high-latitude regions, known for its seasonal reproductive patterns. Our results revealed a significant increase in Ar mRNA expression in wild rats with small testes less than 0.2 g and body weights ranging between 80 and 100 g during the nonbreeding season. Further examinations of Ar expression in the testicular development of R. n. caraco in the laboratory under different day lengths and temperatures that simulating breeding and nonbreeding seasons suggest that the maturation of Sertoli cells depends on the upregulation of Ar expression around a testis weight of 0.07\u20130.18 g, regardless of age and conditions, synchronously accompanying the initiation of the meiotic phase. When Ar expression was suppressed, testicular development was impeded around the stage of Sertoli cell maturation, resulting in decreased spermatogenesis and hindered growth in testis weight. Our findings elucidate how animals control the seasonal inhibition and subsequent recovery of testicular development by regulating Ar expression in R. n. caraco.<\/jats:p>","DOI":"10.3390\/biology14020123","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T09:40:39Z","timestamp":1737711639000},"page":"123","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Androgen Receptor Expression Governs the Seasonal Inhibition of Testicular Development and Subsequent Recovery in Rattus norvegicus caraco"],"prefix":"10.3390","volume":"14","author":[{"given":"Yaqi","family":"Ying","sequence":"first","affiliation":[{"name":"State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lewen","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7057-0549","authenticated-orcid":false,"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-315X","authenticated-orcid":false,"given":"Ying","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8674-1787","authenticated-orcid":false,"given":"Xiaohui","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1177\/0192623314547279","article-title":"Postnatal Development of the Testis in the Rat:Morphologic Study and Correlation of Morphology to Neuroendocrine Parameters","volume":"43","author":"Picut","year":"2015","journal-title":"Toxicol. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1530\/jrf.0.0650053","article-title":"Spermatogenesis in the Grey Squirrel (Sciurus Carolinensis) and Changes during Sexual Regression","volume":"65","author":"Tait","year":"1982","journal-title":"Reproduction"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1093\/biolreprod\/8.4.451","article-title":"Changes in Testicular Leydig Cells and in Plasma Testosterone Levels Among Seasonally Breeding Rock Hyrax","volume":"8","author":"Neaves","year":"1973","journal-title":"Biol. Reprod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s00429-004-0385-2","article-title":"Histological Organization of Roe Deer Testis throughout the Seasonal Cycle: Variable and Constant Components of Tubular and Interstitial Compartment","volume":"208","author":"Streich","year":"2004","journal-title":"Anat. Embryol. (Berl.)"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.4081\/ejh.2015.2456","article-title":"Seasonal Expression of Androgen Receptor, Aromatase, and Estrogen Receptor Alpha and Beta in the Testis of the Wild Ground Squirrel (Citellus Dauricus Brandt)","volume":"59","author":"Li","year":"2015","journal-title":"Eur. J. Histochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.acthis.2017.09.004","article-title":"Seasonal Expression of Luteinizing Hormone Receptor and Follicle Stimulating Hormone Receptor in Testes of the Wild Ground Squirrels (Citellus Dauricus Brandt)","volume":"119","author":"Wang","year":"2017","journal-title":"Acta Histochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/0040-8166(88)90008-0","article-title":"The Seasonal Breeding Hamster as a Model to Study Structure-Function Relationships in the Testis","volume":"20","author":"Bartke","year":"1988","journal-title":"Tissue Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1093\/humupd\/dmq003","article-title":"Molecular Insights into Androgen Actions in Male and Female Reproductive Function from Androgen Receptor Knockout Models","volume":"16","author":"Walters","year":"2010","journal-title":"Hum. Reprod. Update"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.beem.2015.04.006","article-title":"Androgen Receptor Roles in Spermatogenesis and Infertility","volume":"29","author":"Smith","year":"2015","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-3-030-77779-1_9","article-title":"Androgen Actions in the Testis and the Regulation of Spermatogenesis","volume":"1288","author":"Walker","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"25801","DOI":"10.1074\/jbc.M703268200","article-title":"Modulation of Androgen Receptor Activation Function 2 by Testosterone and Dihydrotestosterone","volume":"282","author":"Askew","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1096\/fj.09-138347","article-title":"Androgen Action via Testicular Peritubular Myoid Cells Is Essential for Male Fertility","volume":"23","author":"Welsh","year":"2009","journal-title":"FASEB J."},{"key":"ref_13","first-page":"3","article-title":"Androgen Receptor Structure, Function and Biology: From Bench to Bedside","volume":"37","author":"Davey","year":"2016","journal-title":"Clin. Biochem. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1210\/endo.142.6.8317","article-title":"Murine Germ Cells Do Not Require Functional Androgen Receptors to Complete Spermatogenesis Following Spermatogonial Stem Cell Transplantation","volume":"142","author":"Johnston","year":"2001","journal-title":"Endocrinology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1073\/pnas.0308114100","article-title":"A Sertoli Cell-Selective Knockout of the Androgen Receptor Causes Spermatogenic Arrest in Meiosis","volume":"101","author":"Swinnen","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s12020-007-9015-0","article-title":"Infertility with Defective Spermatogenesis and Steroidogenesis in Male Mice Lacking Androgen Receptor in Leydig Cells","volume":"32","author":"Xu","year":"2007","journal-title":"Endocrine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1126\/science.adp1166","article-title":"The Evolutionary History of Wild and Domestic Brown Rats (Rattus Norvegicus)","volume":"385","author":"Garcia","year":"2024","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s10340-011-0379-9","article-title":"Seasonal Variation in Population Characteristics and Management Implications for Brown Rats (Rattus Norvegicus) within Their Native Range in Harbin, China","volume":"84","author":"Wang","year":"2011","journal-title":"J. Pest Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Li, X., Li, N., Yao, D., Liu, Y., Song, Y., Wang, D., Feng, Z., and Liu, X. (2024). Adaptive Divergence in Reproductive Seasonality and Underlying Physiological Features Fit Rattus Norvegicus to Live as Opportunistic Breeders. Integr. Zool, 1\u201319.","DOI":"10.1111\/1749-4877.12913"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Edelsztein, N.Y., and Rey, R.A. (2019). Importance of the Androgen Receptor Signaling in Gene Transactivation and Transrepression for Pubertal Maturation of the Testis. Cells, 8.","DOI":"10.20944\/preprints201907.0061.v1"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wang, J.M., Li, Z.F., and Yang, W.X. (2022). What Does Androgen Receptor Signaling Pathway in Sertoli Cells During Normal Spermatogenesis Tell Us?. Front. Endocrinol. (Lausanne), 13.","DOI":"10.3389\/fendo.2022.838858"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1111\/1749-4877.12663","article-title":"Pitx2 Suppression at Meiotic Stages Associates with Seasonal Inhibition of Testis Development in Rattus Norvegicus Caraco","volume":"18","author":"Tian","year":"2023","journal-title":"Integr. Zool"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1101\/pdb.prot073411","article-title":"Manual Hematoxylin and Eosin Staining of Mouse Tissue Sections","volume":"2014","author":"Cardiff","year":"2014","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-1-4939-1050-2_3","article-title":"Tissue Processing and Hematoxylin and Eosin Staining","volume":"1180","author":"Feldman","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"SciPy 1.0: Fundamental Algorithms for Scientific Computing in Python","volume":"17","author":"Virtanen","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_26","unstructured":"Skipper, S., and Josef, P. (July, January 28). Statsmodels: Econometric and Statistical Modeling with Python. Proceedings of the 9th Python in Science Conference, Austin, TX, USA."},{"key":"ref_27","first-page":"2825","article-title":"Scikit-Learn: Machine Learning in Python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J. Mach. Learn. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: A 2D Graphics Environment","volume":"9","author":"Hunter","year":"2007","journal-title":"Comput. Sci. Eng."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1172\/JCI119653","article-title":"Regulation of AMH Production in Postnatal Life Rapid Publication Hormonal and Cellular Regulation of Sertoli Cell Anti-M\u00fcllerian Hormone Production in the Postnatal Mouse","volume":"100","author":"Dutertre","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"gaad004","DOI":"10.1093\/molehr\/gaad004","article-title":"Multiomics Approach to Profiling Sertoli Cell Maturation during Development of the Spermatogonial Stem Cell Niche","volume":"29","author":"Voigt","year":"2023","journal-title":"Mol. Hum. Reprod."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1530\/rep.0.1250769","article-title":"Proliferation and Functional Maturation of Sertoli Cells, and Their Relevance to Disorders of Testis Function in Adulthood","volume":"125","author":"Sharpe","year":"2003","journal-title":"Reproduction"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4408","DOI":"10.1210\/jc.2008-0915","article-title":"Physiological Androgen Insensitivity of the Fetal, Neonatal, and Early Infantile Testis Is Explained by the Ontogeny of the Androgen Receptor Expression in Sertoli Cells","volume":"93","author":"Chemes","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s12610-021-00150-8","article-title":"Effect of Androgens on Sertoli Cell Maturation in Human Testis from Birth to Puberty","volume":"31","author":"Lapoirie","year":"2021","journal-title":"Basic Clin. Androl."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4755","DOI":"10.1210\/en.2009-0416","article-title":"Sertoli Cell Androgen Receptor DNA Binding Domain Is Essential for the Completion of Spermatogenesis","volume":"150","author":"Lim","year":"2009","journal-title":"Endocrinology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1210\/er.2008-0025","article-title":"Androgen Receptor Roles in Spermatogenesis and Fertility: Lessons from Testicular Cell-Specific Androgen Receptor Knockout Mice","volume":"30","author":"Wang","year":"2009","journal-title":"Endocr. Rev."},{"key":"ref_36","first-page":"413","article-title":"Androgen Receptor Expression in Sertoli Cells as a Function of Seminiferous Tubule Maturation in the Human Cryptorchid Testis1","volume":"86","author":"Regadera","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.etp.2017.07.001","article-title":"Ameliorative Effect of \u03b1-Tocopherol on Polychlorinated Biphenyl (PCBs) Induced Testicular Sertoli Cell Dysfunction in F1 Prepuberal Rats","volume":"69","author":"Elayapillai","year":"2017","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"nrs-06001","DOI":"10.1621\/nrs.06001","article-title":"AR, the Cell Cycle, and Prostate Cancer","volume":"6","author":"Balk","year":"2008","journal-title":"Nucl. Recept Signal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.4161\/cc.6.11.4353","article-title":"The Complex Role of AR Signaling after Cytotoxic Insult: Implications for Cell Cycle Based Chemotherapeutics","volume":"6","author":"Comstock","year":"2007","journal-title":"Cell Cycle"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.mce.2011.06.033","article-title":"The AR Dependent Cell Cycle: Mechanisms and Cancer Relevance","volume":"352","author":"Schiewer","year":"2012","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/rda.13877","article-title":"AR Regulates Porcine Immature Sertoli Cell Growth via Binding to RNF4 and MiR-124a","volume":"56","author":"Yang","year":"2021","journal-title":"Reprod. Domest. Anim."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1002\/jemt.20754","article-title":"Ontogeny of the Androgen Receptor Expression in the Fetal and Postnatal Testis: Its Relevance on Sertoli Cell Maturation and the Onset of Adult Spermatogenesis","volume":"72","author":"Rey","year":"2009","journal-title":"Microsc. Res. Tech."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1091\/mbc.E20-05-0334","article-title":"Regulation of Meiotic Progression by Sertoli-Cell Androgen Signaling","volume":"31","author":"Larose","year":"2020","journal-title":"Mol. Biol. Cell"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Stanton, P.G., Sluka, P., Foo, C.F.H., Stephens, A.N., Smith, A.I., McLachlan, R.I., and O\u2019Donnell, L. (2012). Proteomic Changes in Rat Spermatogenesis in Response to in Vivo Androgen Manipulation; Impact on Meiotic Cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041718"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1210\/me.2014-1356","article-title":"Research Resource: The Dynamic Transcriptional Profile of Sertoli Cells during the Progression of Spermatogenesis","volume":"29","author":"Zimmermann","year":"2015","journal-title":"Mol. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9312","DOI":"10.1002\/ece3.5477","article-title":"Physiological Dynamics, Reproduction-Maintenance Allocations, and Life History Evolution","volume":"9","author":"English","year":"2019","journal-title":"Ecol. Evol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Rizzoto, G., Sekhar, D., Thundathil, J.C., Chelikani, P.K., and Kastelic, J.P. (2019). Calorie Restriction Modulates Reproductive Development and Energy Balance in Pre-Pubertal Male Rats. Nutrients, 11.","DOI":"10.3390\/nu11091993"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/2\/123\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:35:41Z","timestamp":1759919741000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/2\/123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,24]]},"references-count":47,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["biology14020123"],"URL":"https:\/\/doi.org\/10.3390\/biology14020123","relation":{},"ISSN":["2079-7737"],"issn-type":[{"type":"electronic","value":"2079-7737"}],"subject":[],"published":{"date-parts":[[2025,1,24]]}}}