{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T22:38:52Z","timestamp":1775860732602,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,5,28]],"date-time":"2023-05-28T00:00:00Z","timestamp":1685232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971314"],"award-info":[{"award-number":["81971314"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Advanced Biology"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Previous studies show that prenatal di\u2010(2\u2010ethylhexyl) phthalate (DEHP) exposure induces premature testicular aging. However, the evidence is weak, and the underlying mechanisms remain unclear. p38\/extracellular signal\u2010regulated kinase (ERK)\/c\u2010Jun NH(2)\u2010terminal kinase (JNK) MAPK pathways participate in aging. Leydig cell (LC) senescence results in testicular aging. Whether prenatal DEHP exposure induces premature testicular aging by promoting LC senescence warrants\u00a0further study. Here, male mice undergo prenatal exposure to 500\u00a0mg per kg per day DEHP, and TM3 LCs are treated with 200\u00a0\u00b5<jats:sc>m<\/jats:sc> mono (2\u2010ethylhexyl) phthalate (MEHP). MAPK pathways, testicular toxicity, and senescent phenotypes (<jats:italic>\u03b2<\/jats:italic>\u2010gal activity, p21, p16, and cell cycle) of male mice and LCs are explored. Prenatal DEHP exposure induces premature testicular aging in middle\u2010aged mice (poor genital development, reduced testosterone synthesis, poor semen quality, increased <jats:italic>\u03b2<\/jats:italic>\u2010gal activity, and upregulated expression of p21 and p16). MEHP induces LCs senescence (cell cycle arrest, increased <jats:italic>\u03b2<\/jats:italic>\u2010gal activity, and upregulated expression of p21). p38 and JNK pathways are activated, and the ERK pathway is inactivated. In conclusion, prenatal DEHP exposure induces premature testicular aging by promoting LC senescence through MAPK signaling pathways.<\/jats:p>","DOI":"10.1002\/adbi.202300130","type":"journal-article","created":{"date-parts":[[2023,5,28]],"date-time":"2023-05-28T23:26:20Z","timestamp":1685316380000},"source":"Crossref","is-referenced-by-count":10,"title":["Prenatal DEHP Exposure Induces Premature Testicular Aging by Promoting Leydig Cell Senescence through the MAPK Signaling Pathways"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0991-9219","authenticated-orcid":false,"given":"Xie","family":"Qigen","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery First Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou 510080 China"},{"name":"Department of Andrology First Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou 510080 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cao","family":"Haiming","sequence":"additional","affiliation":[{"name":"Department of Andrology Reproductive Center of the Seventh Affiliated Hospital Sun Yat\u2010Sen University  Shenzhen 518000 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Kai","sequence":"additional","affiliation":[{"name":"Department of Andrology First Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou 510080 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gao","family":"Yong","sequence":"additional","affiliation":[{"name":"Department of Andrology First Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou 510080 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deng","family":"Chunhua","sequence":"additional","affiliation":[{"name":"Department of Andrology First Affiliated Hospital Sun Yat\u2010Sen University  Guangzhou 510080 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,5,28]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12719"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1012119"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202227"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13062045"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2021.147371"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2021.129925"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2020.106228"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2022.133925"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2021.127807"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2021.152985"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfv317"},{"key":"e_1_2_10_12_1","first-page":"96","volume":"156","author":"Barakat R.","year":"2017","journal-title":"Toxicol. 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