{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:05:57Z","timestamp":1791378357890,"version":"4.3.2"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373625"],"award-info":[{"award-number":["82373625"]}],"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":["82173564"],"award-info":[{"award-number":["82173564"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Male fertility depends on normal pubertal development. Di-(2-ethylhexyl) phthalate (DEHP) is a potent antiandrogen chemical, and exposure to DEHP during peripuberty can damage the developing male reproductive system, especially the testis. However, the specific cellular targets and differentiation processes affected by DEHP, which lead to testicular toxicity, remain poorly defined. Herein, we presented the first single-cell transcriptomic profile of the pubertal mouse testis following DEHP exposure. To carry out the experiment, 2 groups (n\u2009=\u20098 each) of 3-week-old male mice were orally administered 0.5% carboxymethylcellulose sodium salt or 100\u2009mg\/kg body weight DEHP daily from postnatal day 21\u201348, respectively. Using single-cell RNA sequencing, a total of 31 distinct cell populations were identified, notably, Sertoli and Leydig cells emerged as important targets of DEHP. DEHP exposure significantly decreased the proportions of Sertoli cell clusters expressing mature Sertoli markers (Sox9 and Ar), and selectively reduced the expression of testosterone synthesis genes in fetal Leydig cells. Through cell\u2013cell interaction analyses, we observed changed numbers of interactions in Sertoli cells 1 (SCs1), Leydig cells 1 (LCs1), and interstitial macrophages, and we also identified cell-specific ligand gene expressions in these clusters, such as Inha, Fyn, Vcam1, and Apoe. Complementary in vitro assays confirmed that DEHP directly reduced the expression of genes related to Sertoli cell adhesion and intercellular communication. In conclusion, peripubertal DEHP exposure reduced the number of mature Sertoli cells and may disrupt testicular steroidogenesis by affecting the testosterone synthesis genes in fetal Leydig cells rather than adult Leydig cells.<\/jats:p>","DOI":"10.1093\/toxsci\/kfae064","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T07:57:10Z","timestamp":1715241430000},"page":"287-298","source":"Crossref","is-referenced-by-count":6,"title":["Single-cell insights into mouse testicular toxicity under peripubertal exposure to di(2-ethylhexyl) phthalate"],"prefix":"10.1093","volume":"200","author":[{"given":"Yongning","family":"Li","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety Risk Assessment , Beijing 100021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaru","family":"Tian","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Food Safety and Health Research Center , Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, West China Hospital, Sichuan University , Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Qiu","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Zaozhuang Maternal and Child Health Care Hospital , Shandong 277100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongjian","family":"Bao","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Zaozhuang Maternal and Child Health Care Hospital , Shandong 277100, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Tang","sequence":"additional","affiliation":[{"name":"China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention , Beijing 100021, China"},{"name":"Center for Global Health, School of Public Health, Nanjing Medical University , Nanjing, Jiangsu 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wan","sequence":"additional","affiliation":[{"name":"Laboratory for Earth Surface Processes, College of 646 Urban and Environmental Sciences, Peking University , Beijing 100871, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Jia","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety Risk Assessment , Beijing 100021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety Risk Assessment , Beijing 100021, China"},{"name":"Guangdong Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Food Safety and Health Research Center , Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,10]]},"reference":[{"key":"2024072914595651200_kfae064-B1","volume-title":"Toxicological profile for di(2-ethylhexyl)phthalate (DEHP)","author":"Agency for Toxic Substances and Disease Registry (ATSDR)","year":"2022"},{"issue":"6","key":"2024072914595651200_kfae064-B2","doi-asserted-by":"crossref","first-page":"65001","DOI":"10.1289\/EHP5045","article-title":"Proposed key characteristics of male reproductive toxicants as an 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