{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T12:11:04Z","timestamp":1775477464353,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32172803"],"award-info":[{"award-number":["32172803"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["20240101255JC"],"award-info":[{"award-number":["20240101255JC"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Jilin Province, China","award":["32172803"],"award-info":[{"award-number":["32172803"]}]},{"name":"Natural Science Foundation of Jilin Province, China","award":["20240101255JC"],"award-info":[{"award-number":["20240101255JC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>5-Hydroxytryptamine (5-HT) is an inhibitory neurotransmitter widely distributed in mammalian tissues, exerting its effects through binding to various receptors. It plays a crucial role in the proliferation of granulosa cells (GCs) and the development of follicles in female animals, however, its effect on porcine follicle development is not clear. The aim of this study is to investigate the expression of 5-HT and its receptors in various parts of the pig ovary, as well as the effect of 5-HT on porcine follicular development by using ELISA, quantitative real-time PCR (qPCR) and EdU assays. Firstly, we examined the levels of 5-HT and its receptors in porcine ovaries, follicles, and GCs. The findings revealed that the expression of different 5-HT receptors varied among follicles of different sizes. To investigate the relationship between 5-HT and its receptors, we exposed the GCs to 5-HT and found a decrease in 5-HT receptor expression compared to the control group. Subsequently, the treatment of GCs with 0.5 \u03bcM, 5 \u03bcM, and 50 \u03bcM 5-HT showed an increase in the expression of cell cycle-related genes, and EdU results indicated cell proliferation after the 0.5 \u03bcM 5-HT treatment. Additionally, the expression of genes involved in E2 synthesis was examined after the treatment of granulosa cells with 0.5 \u03bcM 5-HT. The results showed that CYP19A1 and HSP17\u03b21 expression was decreased. These results suggest that 5-HT might affect the development of porcine follicle by promoting the proliferation of GCs and inhibiting the synthesis of estrogen. This provides a new finding for exploring the effect of 5-HT on follicular development, and lays a foundation for further research on the mechanism of 5-HT in follicles.<\/jats:p>","DOI":"10.3390\/ijms25179596","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T08:46:22Z","timestamp":1725439582000},"page":"9596","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effect of Serotonin (5-Hydroxytryptamine) on Follicular Development in Porcine"],"prefix":"10.3390","volume":"25","author":[{"given":"Yan","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo-Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Sen","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue-Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dao-Zhen","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"An-Tong","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0670-2452","authenticated-orcid":false,"given":"Xue-Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Zoonotic Diseases, College of Veterinary Medicine, Jilin University, Changchun 130062, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1093\/humupd\/dmad005","article-title":"Beyond apoptosis: Evidence of other regulated cell death pathways in the ovary throughout development and life","volume":"29","author":"Stringer","year":"2023","journal-title":"Hum. Reprod. Update"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1093\/toxsci\/kfx047","article-title":"Doxorubicin Has Dose-Dependent Toxicity on Mouse Ovarian Follicle Development, Hormone Secretion, and Oocyte Maturation","volume":"157","author":"Xiao","year":"2017","journal-title":"Toxicol. Sci."},{"key":"ref_3","first-page":"200","article-title":"Initial and cyclic recruitment of ovarian follicles","volume":"21","author":"McGee","year":"2000","journal-title":"Endocr. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1002\/mrd.23576","article-title":"Follicle development in pigs: State of the art","volume":"90","author":"Knox","year":"2022","journal-title":"Mol. Reprod. Dev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Liu, S., Jia, Y., Meng, S., Luo, Y., Yang, Q., and Pan, Z. (2023). Mechanisms of and Potential Medications for Oxidative Stress in Ovarian Granulosa Cells: A Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119205"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.fertnstert.2014.03.029","article-title":"Lipoxin A4 regulates expression of the estrogen receptor and inhibits 17\u03b2-E2 induced p38 mitogen-activated protein kinase phosphorylation in human endometriotic stromal cells","volume":"102","author":"Chen","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1016\/S0015-0282(16)55555-1","article-title":"Interinstitutional variability of follicle-stimulating hormone and E2 levels","volume":"58","author":"Hershlag","year":"1992","journal-title":"Fertil. Steril."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1210\/endo.141.7.7578","article-title":"An age-related ovarian phenotype in mice with targeted disruption of the Cyp 19 (aromatase) gene","volume":"141","author":"Britt","year":"2000","journal-title":"Endocrinology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1021\/cn300154j","article-title":"Life without Peripheral Serotonin: Insights from Tryptophan Hydroxylase 1 Knockout Mice Reveal the Existence of Paracrine\/Autocrine Serotonergic Networks","volume":"4","author":"Amireault","year":"2012","journal-title":"ACS Chem. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1365-2885.2008.00944.x","article-title":"Serotonin: A review","volume":"31","author":"Moses","year":"2008","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1124\/pr.118.015552","article-title":"International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function","volume":"73","author":"Barnes","year":"2021","journal-title":"Pharmacol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s00359-018-1247-3","article-title":"Distribution and dynamic expression of serotonin and dopamine in the nervous system and ovary of Holothuria scabra during ovarian maturation","volume":"204","author":"Chaiyamoon","year":"2018","journal-title":"J. Comp. Physiol. A"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1677\/joe.0.1250433","article-title":"Serotonin enhances oestradiol production by hamster preovulatory follicles in vitro: Effects of experimentally induced atresia","volume":"125","author":"Terranova","year":"1990","journal-title":"J. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/0303-7207(87)90128-6","article-title":"Mechanisms involved in the action of serotonin-induced stimulation of progesterone production by bovine luteal cells in vitro","volume":"51","author":"Battista","year":"1987","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1385\/ENDO:24:2:155","article-title":"Serotonin may alter the pattern of gonadotropin-induced progesterone release of human granulosa cells in superfusion system","volume":"24","author":"Koppan","year":"2004","journal-title":"Endocrine"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Han, Y., Zhang, M., Duan, J., Li, L., Du, J., Cheng, H., Zhang, S., Zhai, Y., An, X., and Li, Q. (2022). Maternal Prepregnancy 5-Hydroxytryptamine Exposure Affects the Early Development of the Fetus. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.761357"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1017\/S0967199407004194","article-title":"Role of follicle stimulating hormone and epidermal growth factor in the development of porcine preantral follicle in vitro","volume":"15","author":"Wu","year":"2007","journal-title":"Zygote"},{"key":"ref_18","first-page":"245","article-title":"Presence of biogenic amines in human follicular fluid and seminal plasma","volume":"39","author":"Sosa","year":"1988","journal-title":"Acta Cient. Venez."},{"key":"ref_19","first-page":"505","article-title":"Uterine and placental 5-HT profile in different gestational period of albino rats","volume":"27","author":"Acharya","year":"1989","journal-title":"Indian J. Exp. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1095\/biolreprod.104.039313","article-title":"Serotonin and its antidepressant-sensitive transport in mouse cumulus-oocyte complexes and early embryos","volume":"73","author":"Amireault","year":"2005","journal-title":"Biol. Reprod."},{"key":"ref_21","first-page":"1277","article-title":"Presence of a 5-HT7 receptor positively coupled to adenylate cyclase activation in human granulosa-lutein cells","volume":"85","author":"Graveleau","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1006\/geno.1999.6059","article-title":"Molecular phenotype of the human oocyte by PCR-SAGE","volume":"63","author":"Neilson","year":"2000","journal-title":"Genomics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1124\/mol.104.010124","article-title":"Intracellular cAMP and calcium signaling by serotonin in mouse cumulus-oocyte complexes","volume":"68","author":"Amireault","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ydbio.2005.08.019","article-title":"The G-protein-coupled receptors GPR3 and GPR12 are involved in cAMP signaling and maintenance of meiotic arrest in rodent oocytes","volume":"287","author":"Hinckley","year":"2005","journal-title":"Dev. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1006\/dbio.1993.1059","article-title":"Development of inositol trisphosphate-induced calcium release mechanism during maturation of hamster oocytes","volume":"156","author":"Fujiwara","year":"1993","journal-title":"Dev. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6619","DOI":"10.1002\/jcp.30305","article-title":"TGF-\u03b21 stimulates aromatase expression and E2 production through SMAD2 and ERK1\/2 signaling pathways in human granulosa-lutein cells","volume":"236","author":"Cheng","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1677\/joe.1.06549","article-title":"The susceptibility of granulosa cells to apoptosis is influenced by oE2 and the cell cycle","volume":"189","author":"Quirk","year":"2006","journal-title":"J. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/0024-3205(93)90713-D","article-title":"Serotonin stimulates steroidogenesis in rat preovulatory follicles: Involvement of 5-HT2 receptor","volume":"53","author":"Tanaka","year":"1993","journal-title":"Life Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.tjog.2014.10.007","article-title":"Sleep deprivation enhances peripheral serotonin secretion to regulate the large follicle steroidogenesis of rats","volume":"54","author":"Yang","year":"2015","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_30","first-page":"958","article-title":"Effect of serotonin and antiserotonin preparations on the development of early stages of mice embryos cultivated in vitro","volume":"188","author":"Leonov","year":"1969","journal-title":"Dokl. Akad. Nauk. SSSR"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e12546","DOI":"10.1111\/jpi.12546","article-title":"Effects of melatonin on the synthesis of estradiol and gene expression in pig granulosa cells","volume":"66","author":"Liu","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1095\/biolreprod.109.077016","article-title":"Significant Improvement in Cloning Efficiency of an Inbred Miniature Pig by Histone Deacetylase Inhibitor Treatment after Somatic Cell Nuclear Transfer","volume":"81","author":"Zhao","year":"2009","journal-title":"Biol. Reprod."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9596\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:48:37Z","timestamp":1760111317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/17\/9596"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,4]]},"references-count":32,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["ijms25179596"],"URL":"https:\/\/doi.org\/10.3390\/ijms25179596","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,4]]}}}