{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:55:05Z","timestamp":1773273305647,"version":"3.50.1"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>This study aimed to explore the effects of neonatal vitamin A (VA) supplementation on testis development and spermatogenesis. A total of 32 newborn lambs were intramuscularly injected with corn oil (control group) or corn oil + 2500 IU\/kg BW VA (VA group). They were slaughtered and sampled at 3 weeks and 8 months of age to analyze spermatogenesis, cell proliferation, hormone secretion, antioxidant status of the testis, and adult sheep sperm parameters. Compared with the control group, the expression of spermatogonial differentiation-related genes in VA group was up-regulated (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). Testis weight, seminiferous tubule diameter, number of spermatogonium and spermatocyte, and sperm density increased significantly in VA group at 8 months of age (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). Neonatal VA injection upregulated the expression of the cell proliferation marker <jats:italic>PCNA<\/jats:italic> and cell cycle-related genes in the testis (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). VA increased the concentrations of testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in the serum and upregulated steroidogenesis-related genes in the testis (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). The antioxidant levels in the VA group were maintained at high levels. The total antioxidant capacity (T-AOC), antioxidant enzyme content and antioxidant-related genes were increased in the testis (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). Furthermore, neonatal VA injection activated retinoic acid (RA) signaling to maintain the blood-testosterone barrier (BTB) in the testis of 3-week-old sheep. AMP-activated protein kinase (AMPK) and protein kinase B (AKT) signaling were also modulated in the sheep testis (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). Taken together, VA supplementation in newborn rams promotes testis development and spermatogenesis to improve fertility.<\/jats:p>","DOI":"10.3389\/fvets.2024.1370576","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T12:54:03Z","timestamp":1714654443000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Neonatal vitamin A supplementation improves sheep fertility potential"],"prefix":"10.3389","volume":"11","author":[{"given":"Yating","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengkang","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiamin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weipeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangdong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyang","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junxing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1002\/ncp.10376","article-title":"The role of vitamin A in wound healing","volume":"34","author":"Polcz","year":"2019","journal-title":"Nutr Clin Pract."},{"key":"B2","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1172\/JCI41303","article-title":"The key role of vitamin A in spermatogenesis","volume":"120","author":"Hogarth","year":"2010","journal-title":"J Clin Invest."},{"key":"B3","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1262\/jrd.2013-058","article-title":"Vitamin A deprivation affects the progression of the spermatogenic wave and initial formation of the blood-testis barrier, resulting in irreversible testicular degeneration in mice","volume":"59","author":"Chihara","year":"2013","journal-title":"J Reprod Dev."},{"key":"B4","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1096\/fasebj.10.9.8801176","article-title":"A decade of molecular biology of retinoic acid receptors","volume":"10","author":"Chambon","year":"1996","journal-title":"FASEB J."},{"key":"B5","doi-asserted-by":"publisher","first-page":"108522","DOI":"10.1016\/j.steroids.2019.108522","article-title":"Crosstalk in the non-classical signal transduction of testosterone and retinol in immature rat testes","volume":"153","author":"do Nascimento","year":"2020","journal-title":"Steroids"},{"key":"B6","first-page":"34","article-title":"Gonadotropin regulation of retinoic acid activity in the testis","volume":"56","author":"Nourashrafeddin","year":"2018","journal-title":"Acta Med Iran."},{"key":"B7","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3109\/19396360902896844","article-title":"Temporal profiling of rat transcriptomes in retinol-replenished vitamin A-deficient testis","volume":"55","author":"Doyle","year":"2009","journal-title":"Syst Biol Reprod Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1530\/REP-14-0481","article-title":"Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling","volume":"149","author":"Chen","year":"2015","journal-title":"Reproduction."},{"key":"B9","doi-asserted-by":"publisher","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":"2012","journal-title":"Pharmacol Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1210\/er.2014-1101","article-title":"The mammalian blood-testis barrier: its biology and regulation","volume":"36","author":"Mruk","year":"2015","journal-title":"Endocr Rev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1016\/j.cub.2017.07.067","article-title":"Spermatogenesis","volume":"27","author":"Nishimura","year":"2017","journal-title":"Curr Biol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1093\/biolre\/ioac148","article-title":"Synchronizing spermatogenesis in the mouse","volume":"107","author":"Griswold","year":"2022","journal-title":"Biol Reprod."},{"key":"B13","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12958-020-00686-w","article-title":"FSH regulates RA signaling to commit spermatogonia into differentiation pathway and meiosis","volume":"19","author":"Khanehzad","year":"2021","journal-title":"Reprod Biol Endocrinol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"352","DOI":"10.3390\/cells11030352","article-title":"Action and interaction between retinoic acid signaling and blood-testis barrier function in the spermatogenesis cycle","volume":"11","author":"Zhou","year":"2022","journal-title":"Cells."},{"key":"B15","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1096\/fasebj.30.1_supplement.124.2","article-title":"Maternal vitamin A supplementation expands adipose progenitor population through promoting vascular development","author":"Wang","year":"2016","journal-title":"FASEB J 30."},{"key":"B16","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s40104-018-0296-3","article-title":"Neonatal vitamin A injection promotes cattle muscle growth and increases oxidative muscle fibers","volume":"9","author":"Wang","year":"2018","journal-title":"J Anim Sci Biotechnol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.aninu.2023.05.011","article-title":"Vitamin A injection at birth improves muscle growth in lambs","volume":"14","author":"Song","year":"2023","journal-title":"Anim Nutr."},{"key":"B18","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.theriogenology.2022.04.016","article-title":"Cross-talk between NOTCH2 and BMP4\/SMAD signaling pathways in bovine follicular granulosa cells","volume":"187","author":"Li","year":"2022","journal-title":"Theriogenology."},{"key":"B19","doi-asserted-by":"publisher","first-page":"775","DOI":"10.3390\/biom9120775","article-title":"Retinoic acid and germ cell development in the ovary and testis","volume":"9","author":"Endo","year":"2019","journal-title":"Biomolecules."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1016\/j.celrep.2018.06.111","article-title":"Retinoic acid antagonizes testis development in mice","volume":"24","author":"Bowles","year":"2018","journal-title":"Cell Rep."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1016\/j.gendis.2021.03.006","article-title":"Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RAR\u03b1 to restore spermatogenesis in cryptorchid infertile rats","volume":"9","author":"Long","year":"2021","journal-title":"Genes Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1095\/biolreprod.112.106526","article-title":"Minimal concentrations of retinoic acid induce stimulation by retinoic acid 8 and promote entry into meiosis in isolated pregonadal and gonadal mouse primordial germ cells","volume":"88","author":"Tedesco","year":"2013","journal-title":"Biol Reprod."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1016\/j.fertnstert.2014.08.004","article-title":"Inhibition of mammalian target of rapamycin signaling pathway decreases retinoic acid stimulated gene 8 expression in adult mouse testis","volume":"102","author":"Sahin","year":"2014","journal-title":"Fertil Steril."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.3390\/genes12111812","article-title":"PCNA loaders and unloaders-one ring that rules them all","volume":"12","author":"Arbel","year":"2021","journal-title":"Genes."},{"key":"B25","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.cell.2018.02.014","article-title":"Regulation of cell cycle to stimulate adult cardiomyocyte proliferation and cardiac regeneration","volume":"173","author":"Mohamed","year":"2018","journal-title":"Cell."},{"key":"B26","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1111\/j.1750-3639.1999.tb00532.x","article-title":"Amplification and expression of cyclin D genes (CCND1, CCND2 and CCND3) in human malignant gliomas","volume":"9","author":"B\u00fcschges","year":"1999","journal-title":"Brain Pathol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/bs.acr.2020.02.002","article-title":"Cyclin D-CDK4\/6 functions in cancer","volume":"148","author":"Gao","year":"2020","journal-title":"Adv Cancer Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1038\/s41418-022-00988-z","article-title":"Cell cycle regulation: p53-p21-RB signaling","volume":"29","author":"Engeland","year":"2022","journal-title":"Cell Death Differ."},{"key":"B29","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.dnarep.2016.04.008","article-title":"Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage","volume":"42","author":"Karimian","year":"2016","journal-title":"DNA Repair."},{"key":"B30","doi-asserted-by":"publisher","first-page":"101365","DOI":"10.1016\/j.jbc.2021.101365","article-title":"Tumor suppressor p53 promotes ferroptosis in oxidative stress conditions independent of modulation of ferroptosis by p21, CDKs, RB, and E2F","volume":"297","author":"Kuganesan","year":"2021","journal-title":"J Biol Chem."},{"key":"B31","doi-asserted-by":"publisher","first-page":"539","DOI":"10.2174\/1566524020666201203164910","article-title":"The role of the PI3K\/AKT\/mTOR signalling pathway in male reproduction","volume":"21","author":"Deng","year":"2021","journal-title":"Curr Mol Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"125036","DOI":"10.1016\/j.chemosphere.2019.125036","article-title":"Dimethoate blocks pubertal differentiation of Leydig cells in rats","volume":"241","author":"Dong","year":"2020","journal-title":"Chemosphere."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1242\/dev.160465","article-title":"Retinoic acid receptor signaling is necessary in steroidogenic cells for normal spermatogenesis and epididymal function","author":"Jauregui","year":"2018","journal-title":"Development."},{"key":"B34","doi-asserted-by":"publisher","first-page":"10132","DOI":"10.1038\/srep10132","article-title":"Retinoic acid receptor beta and angiopoietin-like protein 1 are involved in the regulation of human androgen biosynthesis","volume":"5","author":"Udhane","year":"2015","journal-title":"Sci Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1080\/07315724.2017.1387877","article-title":"Serum retinol, folic acid, and copper are associated with sperm abnormalities in men with obesity","volume":"37","author":"Calder\u00f3n","year":"2018","journal-title":"J Am Coll Nutr."},{"key":"B36","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1093\/humupd\/dml054","article-title":"The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility","volume":"13","author":"Ebisch","year":"2007","journal-title":"Hum Reprod Update."},{"key":"B37","doi-asserted-by":"publisher","first-page":"787","DOI":"10.29252\/ijrm.13.12.787","article-title":"Serum levels of lycopene, beta-carotene, and retinol and their correlation with sperm DNA damage in normospermic and infertile men","volume":"13","author":"Ghyasvand","year":"2015","journal-title":"Int J Reprod Biomed."},{"key":"B38","doi-asserted-by":"publisher","first-page":"14804","DOI":"10.1074\/jbc.M117.788901","article-title":"Hydrogen peroxide produced by superoxide dismutase SOD-2 activates sperm in Caenorhabditis elegans","volume":"292","author":"Sakamoto","year":"2017","journal-title":"J Biol Chem."},{"key":"B39","doi-asserted-by":"publisher","first-page":"e8361","DOI":"10.7717\/peerj.8361","article-title":"Flavonoids from Epimedium pubescens: extraction and mechanism, antioxidant capacity and effects on CAT and GSH-Px of Drosophila melanogaster","volume":"8","author":"Yang","year":"2020","journal-title":"PeerJ."},{"key":"B40","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1515\/jvetres-2017-0067","article-title":"MDA and GSH-Px activity in transition dairy cows under seasonal variations and their relationship with reproductive performance","volume":"61","author":"Colakoglu","year":"2017","journal-title":"J Vet Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1111\/andr.12722","article-title":"Cycles, waves, and pulses: Retinoic acid and the organization of spermatogenesis","volume":"8","author":"Gewiss","year":"2020","journal-title":"Andrology."},{"key":"B42","doi-asserted-by":"publisher","first-page":"10845","DOI":"10.1038\/ncomms10845","article-title":"ALDH1A1 provides a source of meiosis-inducing retinoic acid in mouse fetal ovaries","volume":"7","author":"Bowles","year":"2016","journal-title":"Nat Commun."},{"key":"B43","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.gene.2017.10.032","article-title":"Sertoli cell specific knockdown of RAR-related orphan receptor (ROR) alpha at puberty reduces sperm count in rats","volume":"641","author":"Mandal","year":"2018","journal-title":"Gene."},{"key":"B44","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s12199-021-01021-4","article-title":"Circadian effects of ionizing radiation on reproductive function and clock genes expression in male mouse","volume":"26","author":"Qin","year":"2021","journal-title":"Environ Health Prev Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1111\/j.1365-2443.1997.119gc0317.x","article-title":"Transcriptional regulation of a Purkinje cell-specific gene through a functional interaction between ROR alpha and RAR","volume":"2","author":"Matsui","year":"1997","journal-title":"Genes Cells."},{"key":"B46","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/s41419-019-1782-z","article-title":"Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis","volume":"10","author":"Ni","year":"2019","journal-title":"Cell Death Dis."},{"key":"B47","doi-asserted-by":"publisher","first-page":"144635","DOI":"10.1016\/j.gene.2020.144635","article-title":"The dynamics and regulation of microfilament during spermatogenesis","volume":"744","author":"Yang","year":"2020","journal-title":"Gene."},{"key":"B48","doi-asserted-by":"publisher","first-page":"593005","DOI":"10.3389\/fcell.2020.593005","article-title":"Roles of AMP-activated protein kinase (AMPK) in mammalian reproduction","volume":"8","author":"Yang","year":"2020","journal-title":"Front Cell Dev Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.mce.2016.01.001","article-title":"Specific deletion of AMP-activated protein kinase (\u03b11AMPK) in mouse Sertoli cells modifies germ cell quality","volume":"423","author":"Bertoldo","year":"2016","journal-title":"Mol Cell Endocrinol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"621","DOI":"10.14670\/HH-18-457","article-title":"The PI3K\/AKT signaling pathway: How does it regulate development of Sertoli cells and spermatogenic cells?","volume":"37","author":"Chen","year":"2022","journal-title":"Histol. Histopathol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.envpol.2019.04.114","article-title":"Icariin attenuate microcystin-LR-induced gap junction injury in Sertoli cells through suppression of Akt pathways","volume":"251","author":"Zhou","year":"2019","journal-title":"Environ Pollut."},{"key":"B52","doi-asserted-by":"publisher","first-page":"109824","DOI":"10.1016\/j.ecoenv.2019.109824","article-title":"Responses of the proteome in testis of mice exposed chronically to environmentally relevant concentrations of Microcystin-LR","volume":"187","author":"Zhou","year":"2020","journal-title":"Ecotoxicol Environ Saf."},{"key":"B53","doi-asserted-by":"publisher","first-page":"224","DOI":"10.3389\/fendo.2019.00224","article-title":"Molecular mechanisms and signaling pathways involved in sertoli cell proliferation","volume":"10","author":"Meroni","year":"2019","journal-title":"Front Endocrinol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1152\/ajpendo.00477.2011","article-title":"Signal transduction pathways in FSH regulation of rat Sertoli cell proliferation","volume":"302","author":"Riera","year":"2012","journal-title":"Am J Physiol Endocrinol Metab."},{"key":"B55","doi-asserted-by":"publisher","first-page":"e13220","DOI":"10.1111\/cpr.13220","article-title":"Long noncoding RNAs regulated spermatogenesis in varicocele-induced spermatogenic dysfunction","volume":"55","author":"Wang","year":"2022","journal-title":"Cell Prolif."},{"key":"B56","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.ydbio.2015.08.004","article-title":"Mammalian target of rapamycin complex 1 (mTORC1) Is required for mouse spermatogonial differentiation in vivo","volume":"407","author":"Busada","year":"2015","journal-title":"Dev Biol."}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2024.1370576\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T12:54:12Z","timestamp":1714654452000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2024.1370576\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,2]]},"references-count":56,"alternative-id":["10.3389\/fvets.2024.1370576"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2024.1370576","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,2]]},"article-number":"1370576"}}