{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:09:34Z","timestamp":1788408574802,"version":"build-2803163510"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T00:00:00Z","timestamp":1693612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Priority Research Area","award":["B.1.7.2021"],"award-info":[{"award-number":["B.1.7.2021"]}]},{"name":"Strategic Programme Excellence Initiative at Jagiellonian University in Krakow, Poland"},{"DOI":"10.13039\/501100014434","name":"Polish National Agency for Academic Exchange","doi-asserted-by":"publisher","award":["BPN\/BFR\/2022\/1\/00007"],"award-info":[{"award-number":["BPN\/BFR\/2022\/1\/00007"]}],"id":[{"id":"10.13039\/501100014434","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Spexin (SPX) is a novel neuropeptide and adipokine negatively correlated with obesity and insulin resistance. A recent study investigated expression and regulatory function of SPX in the hypothalamus and pituitary; however, the effect on ovarian function is still unknown. The aim of this study was to characterize the expression of SPX and its receptors, galanin receptors 2 and 3 (GALR2\/3), in the human ovary and to study its in vitro effect on granulosa cells (GC) function. Follicular fluid (FF) and GC were obtained from normal weight and obese healthy and diagnosed with polycystic ovarian syndrome (PCOS) women. Expression of SPX and GALR2\/3 in the ovary was studied by qPCR, western blot, and immunohistochemistry. The level of SPX in FF was assessed by enzyme-linked immunosorbent assay. The in vitro effect of recombinant human SPX on GC proliferation, steroidogenesis, and signaling pathways (MAP3\/1, STAT3, AKT, PKA) was analyzed. Moreover, GC proliferation and estradiol (E2) secretion were measured with and without an siRNA against GALR2\/3 and pharmacological inhibition of the above kinases. The results showed that both the SPX concentration in FF and its gene expression were decreased in GC of obese and PCOS women, while the protein expression of GALR2\/3 was increased. We noted that SPX reduced GC proliferation and steroidogenesis; these effects were mediated by GALR2\/3 and kinases MAP3\/1, AKT, and STAT3 for proliferation or kinases MAP3\/1 and PKA for E2 secretion. The obtained data clearly documented that SPX is a novel regulator of human ovarian physiology and possibly plays a role in PCOS pathogenesis.<\/jats:p>","DOI":"10.1093\/biolre\/ioad108","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T16:16:44Z","timestamp":1693325804000},"page":"705-719","source":"Crossref","is-referenced-by-count":19,"title":["Spexin role in human granulosa cells physiology and PCOS: expression and negative impact on steroidogenesis and proliferation"],"prefix":"10.1093","volume":"109","author":[{"given":"Patrycja","family":"Kurowska","sequence":"first","affiliation":[{"name":"Laboratory of Physiology and Toxicology of Reproduction , Institute of Zoology and Biomedical Research, , Krakow , Poland"},{"name":"Jagiellonian University in Krakow , Institute of Zoology and Biomedical Research, , Krakow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Dawid","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Toxicology of Reproduction , Institute of Zoology and Biomedical Research, , Krakow , Poland"},{"name":"Jagiellonian University in Krakow , Institute of Zoology and Biomedical Research, , Krakow , Poland"},{"name":"Doctoral School of Exact and Natural Sciences, Jagiellonian University in Krakow , Krakow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Oprocha","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Toxicology of Reproduction , Institute of Zoology and Biomedical Research, , Krakow , Poland"},{"name":"Jagiellonian University in Krakow , Institute of Zoology and Biomedical Research, , Krakow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Respekta","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Toxicology of Reproduction , Institute of Zoology and Biomedical Research, , Krakow , Poland"},{"name":"Jagiellonian University in Krakow , Institute of Zoology and Biomedical Research, , Krakow , Poland"},{"name":"Doctoral School of Exact and Natural Sciences, Jagiellonian University in Krakow , Krakow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo\u00efse","family":"Serra","sequence":"additional","affiliation":[{"name":"National Research Institute for Agriculture , Food and the Environment, , Nouzilly , France"},{"name":"UMR85, Unit\u00e9 Physiologie de la Reproduction et des Comportements , Food and the Environment, , Nouzilly , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Estienne","sequence":"additional","affiliation":[{"name":"National Research Institute for Agriculture , Food and the Environment, , Nouzilly , France"},{"name":"UMR85, Unit\u00e9 Physiologie de la Reproduction et des Comportements , Food and the Environment, , Nouzilly , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Pawlicki","sequence":"additional","affiliation":[{"name":"Center of Experimental and Innovative Medicine, University of Agriculture in Krakow , Krakow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Kotula-Balak","sequence":"additional","affiliation":[{"name":"Department of Animal Anatomy and Preclinical Sciences, University Centre of Veterinary Medicine JU-UA, University of Agriculture in Krakow , Krakow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Gu\u00e9rif","sequence":"additional","affiliation":[{"name":"National Research Institute for Agriculture , Food and the Environment, , Nouzilly , France"},{"name":"UMR85, Unit\u00e9 Physiologie de la Reproduction et des Comportements , Food and the Environment, , Nouzilly , France"},{"name":"Reproductive Medicine and Biology Department, University Hospital of Tours , Tours , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle","family":"Dupont","sequence":"additional","affiliation":[{"name":"National Research Institute for Agriculture , Food and the Environment, , Nouzilly , France"},{"name":"UMR85, Unit\u00e9 Physiologie de la Reproduction et des Comportements , Food and the Environment, , Nouzilly , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Rak","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology and Toxicology of Reproduction , Institute of Zoology and Biomedical Research, , Krakow , Poland"},{"name":"Jagiellonian University in Krakow , Institute of Zoology and Biomedical Research, , Krakow , Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,2]]},"reference":[{"key":"2023111518472009000_ref1","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1101\/gr.5755407","article-title":"Identification of novel peptide hormones in the human proteome by hidden Markov model screening","volume":"17","author":"Mirabeau","year":"2007","journal-title":"Genome Res"},{"key":"2023111518472009000_ref2","doi-asserted-by":"crossref","first-page":"e681646","DOI":"10.3389\/fendo.2021.681646","article-title":"Wong AOL. Mouse Spexin:SLive_RefAppend (I) NMR solution structure, docking models for receptor binding, and histological expression at tissue level","volume":"12","author":"Wong","year":"2021","journal-title":"Front Endocrinol"},{"key":"2023111518472009000_ref3","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1369\/jhc.2010.956300","article-title":"Spexin expression in normal rat tissues","volume":"58","author":"Porzionato","year":"2010","journal-title":"J Histochem Cytochem"},{"key":"2023111518472009000_ref4","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1210\/en.2013-2106","article-title":"Coevolution of the spexin\/galanin\/kisspeptin family: spexin activates galanin receptor type II and III","volume":"155","author":"Kim","year":"2014","journal-title":"Endocrinology"},{"key":"2023111518472009000_ref5","article-title":"Spexin enhances bowel movement through activating L-type voltage-dependent calcium channel via galanin receptor 2 in 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