{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:21:13Z","timestamp":1784557273521,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:p>\n                    Obesity is strongly linked to male infertility. Apoptotic inflammatory response caused by oxidative stress in testicular spermatogenic cells is one of the important causes of obesity-related male infertility. As bioactive peptide is secreted by the pituitary gland, pituitary adenylate cyclase activating polypeptide (PACAP) has a powerful triple role of anti-oxidation, anti-apoptosis, and anti-inflammation, and it is involved in the male reproduction regulation, but the specific mechanism remains unknown. The purpose of this study is to explore the role of PACAP in obesity-related male infertility. In cellular level experiments, mouse spermatocytes (GC-2) were treated with palmitate (PA) to establish an high-fat injury cell model\n                    <jats:italic>in vitro<\/jats:italic>\n                    and then treated with PACAP. In animal-level experiments, C57BL\/6 male mice were fed with a high-fat diet (HFD) to induce obesity and subsequently treated with PACAP. The cell mechanism studies show that PACAP selectively binded to the PAC1 receptor to attenuate palmitic acid-induced mouse spermatogenic cell (GC-2) oxidative damage and apoptotic inflammatory response via the PKA\/ERK\/Nrf2 signaling axis. However, this mechanism was inhibited in GC-2 cells inhibiting the activity of Nrf2. The animal experiment studies show that PACAP treatment ameliorated obesity characteristics, including body weight, epididymal adipose weight, testes\/body weight, serum lipids levels, and reproductive hormone levels\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Additionally, PACAP was shown to improve the reproductive function of the obese mice, which was characterized by improved testis morphology and sperm parameters via Keap1\/Nrf2\/ARE pathway. These beneficial effects of PACAP were abolished in obese mice with testes-specific knockdown of Nrf2. Our data suggested that PACAP could ameliorate fertility in obese male mice and may be a promising candidate drug for obesity-induced male infertility.\n                  <\/jats:p>","DOI":"10.1530\/joe-20-0316","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T09:42:26Z","timestamp":1613727746000},"page":"337-354","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":15,"title":["PACAP ameliorates the fertility of obese mice through PAC1\/PKA\/ERK\/Nrf2 signal axis"],"prefix":"10.1530","volume":"248","author":[{"given":"Wailan","family":"Shan","sequence":"first","affiliation":[{"name":"1Institute of Biomedicine, Department of Cellular Biology, Jinan University, Guangzhou, China"},{"name":"2National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyin","family":"Lu","sequence":"additional","affiliation":[{"name":"1Institute of Biomedicine, Department of Cellular Biology, Jinan University, Guangzhou, China"},{"name":"2National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biqian","family":"Ou","sequence":"additional","affiliation":[{"name":"1Institute of Biomedicine, Department of Cellular Biology, Jinan University, Guangzhou, China"},{"name":"2National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Feng","sequence":"additional","affiliation":[{"name":"1Institute of Biomedicine, Department of Cellular Biology, Jinan University, Guangzhou, China"},{"name":"2National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixian","family":"Wang","sequence":"additional","affiliation":[{"name":"1Institute of Biomedicine, Department of Cellular Biology, Jinan University, Guangzhou, China"},{"name":"2National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixian","family":"Li","sequence":"additional","affiliation":[{"name":"1Institute of Biomedicine, Department of Cellular Biology, Jinan University, Guangzhou, China"},{"name":"2National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Lu","sequence":"additional","affiliation":[{"name":"3The First Affiliated Hospital of Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Ma","sequence":"additional","affiliation":[{"name":"1Institute of Biomedicine, Department of Cellular Biology, Jinan University, Guangzhou, China"},{"name":"2National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/248\/3\/JOE-20-0316.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/248\/3\/JOE-20-0316.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:57:17Z","timestamp":1784555837000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/248\/3\/337-354\/5407"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":0,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1530\/joe-20-0316","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3]]}}}