{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:19:37Z","timestamp":1790957977872,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:00:00Z","timestamp":1670371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>The increased hypothalamic neurokinin B (NKB) level may contribute to the hyperactive LH pulse secretion in Polycystic ovary syndrome (PCOS). However, the expression and role of the neurokinin B\u2010neurokinin 3 receptor (NKB\u2010NK3R) system in the local ovarian tissue of PCOS have not been clarified. We constructed in vivo and in vitro models to elucidate the mechanism of the NKB\u2010NK3R pathway in reproductive endocrine disorders of PCOS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of study<\/jats:title><jats:p>The granulosa cell line\u2010KGN cells were set in palmitic acid (PA) and dihydrotestosterone (DHT) to simulate the PCOS\u2010like conditions. And we used the high\u2010fat\/high\u2010glucose diet to build a PCOS\u2010like mice model and neurokinin 3 receptor antagonist (NK3Ra) was administered to half of the mice. The expression of the NKB\u2010NK3R system, mitochondrial functions, hormone levels, and inflammatory state was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The PCOS\u2010like stimulations induced the NKB\u2010NK3R system and MAPK\u2010ERK pathway overexpression in KGN cells, in an approximate dose and time\u2010dependent manner. The NKB\u2010NK3R system overactivated the MAPK\u2010ERK pathway to increase NNT overexpression, disturb NADH\/NADPH pools, aggravate the oxidation state, and decrease ATP production. With overexpression of the NKB\u2010NK3R system in the local ovarian tissue, ovulatory dysfunction, progesterone deficiency, and pro\u2010inflammatory states were apparent in PCOS\u2010like mice. Antagonizing the receptor, NK3R, reversed the adverse reproductive endocrine phenotypes via improving mitochondrial dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In addition to the central regulation, local ovarian overexpression of the NKB\u2010NK3R system participated in the adverse reproductive endocrine phenotypes, supporting the therapeutic implications of NK3Ra for PCOS.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13663","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T13:19:57Z","timestamp":1669900797000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The overexpression of neurokinin B\u2013neurokinin 3 receptor system exerts direct effects on the ovary under PCOS\u2010like conditions to interfere with mitochondrial function"],"prefix":"10.1111","volume":"89","author":[{"given":"Fei","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Gynecology Obstetrics and Gynecology Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taniya","family":"Fernando","sequence":"additional","affiliation":[{"name":"Department of Gynecology Obstetrics and Gynecology Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2512-9703","authenticated-orcid":false,"given":"Xiaoyong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Gynecology Obstetrics and Gynecology Hospital of Fudan University  Shanghai China"},{"name":"Laboratory for Reproductive Immunology Hospital of Obstetrics and Gynecology Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingli","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Gynecology Obstetrics and Gynecology Hospital of Fudan University  Shanghai China"},{"name":"Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.08.015"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2350"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.82.7.4105"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioab103"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.62455"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-16-0378"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqaa018"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod65.2.538"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.02.021"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deu247"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.116.139881"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2007.07.004"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/den090"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des191"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa108"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2021.06.013"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.892125"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.68930"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe0237"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5843"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-022-00531-5"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10528-022-10238-z"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13479"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1196"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqab020"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2019.11.001"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101650"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-018-1338-7"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.05.006"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1354"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dms059"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.05.013"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaaa081"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1938914"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2540001"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.04.035"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2020.10.009"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2017.12.020"},{"key":"e_1_2_9_40_1","doi-asserted-by":"crossref","unstructured":"Wawrzkiewicz\u2010Ja\u0142owieckaA KowalczykK TrybekP et\u00a0al. InSearch of new therapeutics\u2010molecular aspects of the PCOS pathophysiology: genetics hormones metabolism and beyond.Int J Mol Sci.2020;21(19).","DOI":"10.3390\/ijms21197054"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84216-7"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2017.09.002"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-021-00749-6"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.29252\/ijrm.15.8.491"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2017.10.010"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.repbio.2020.07.004"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.03.06.db05-0453"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2015-1409"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-3621"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-1202"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-01306"}],"container-title":["American Journal of Reproductive Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aji.13663","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/aji.13663","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aji.13663","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T02:15:58Z","timestamp":1692324958000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aji.13663"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,7]]},"references-count":50,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1111\/aji.13663"],"URL":"https:\/\/doi.org\/10.1111\/aji.13663","archive":["Portico"],"relation":{},"ISSN":["1046-7408","1600-0897"],"issn-type":[{"value":"1046-7408","type":"print"},{"value":"1600-0897","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,7]]},"assertion":[{"value":"2022-08-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13663"}}