PMID- 33912029 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210430 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 12 DP - 2021 TI - The Production of Testosterone and Gene Expression in Neonatal Testes of Rats Exposed to Diisoheptyl Phthalate During Pregnancy is Inhibited. PG - 568311 LID - 10.3389/fphar.2021.568311 [doi] LID - 568311 AB - Background: Diisoheptyl phthalate (DIHP) is a phthalate plasticizer, which is a branched phthalate. Here, we reported the effects of gestational exposure to DIHP on testis development in male rats. Methods: Pregnant Sprague-Dawley rats were orally fed with vehicle (corn oil, control) or DIHP (10, 100, 500, and 1,000 mg/kg) from gestational day (GD) 12-21. At GD21, serum testosterone levels, the number and distribution of fetal Leydig cells, and testicular mRNA and protein levels, the incidence of multinucleated gonocytes, and focal testicular hypoplasia in the neonatal testis were measured. Results: DIHP increased the fetal Leydig cell cluster size and decreased the fetal Leydig cell size with LOAEL of 10 mg/kg. DIHP did not affect the fetal Leydig cell number. DIHP significantly lowered serum testosterone levels, down-regulated the expression of steroidogenesis-related genes (Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3) and testis descent-related gene (Insl3) as well as protein levels of cholesterol side-chain cleavage enzyme (CYP11A1) and insulin-like 3 (INSL3). DIHP dose-dependently increased the percentage of multinucleated gonocytes with the low observed adverse-effect level (LOAEL) of 100 mg/kg. DIHP induced focal testicular hypoplasia. Conclusion: Gestational exposure to DIHP causes testis dysgenesis in rats. CI - Copyright (c) 2021 Ji, Wen, Ni, Zhu, Wang, Li, Zhong and Ge. FAU - Ji, Bin AU - Ji B AD - Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, China. FAU - Wen, Zina AU - Wen Z AD - Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China. AD - Chengdu Jinjiang Maternal and Child Health Hospital and Chengdu Xi'nan Gynecology Hospital, Chengdu, China. FAU - Ni, Chaobo AU - Ni C AD - Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, China. FAU - Zhu, Qiqi AU - Zhu Q AD - Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China. FAU - Wang, Yiyan AU - Wang Y AD - Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, China. FAU - Li, Xiaoheng AU - Li X AD - Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, China. FAU - Zhong, Ying AU - Zhong Y AD - Chengdu Jinjiang Maternal and Child Health Hospital and Chengdu Xi'nan Gynecology Hospital, Chengdu, China. FAU - Ge, Ren-Shan AU - Ge RS AD - Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, China. AD - Chengdu Jinjiang Maternal and Child Health Hospital and Chengdu Xi'nan Gynecology Hospital, Chengdu, China. LA - eng PT - Journal Article DEP - 20210412 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC8072358 OTO - NOTNLM OT - diisoheptyl phthalate OT - fetal leydig cell OT - leydig cell cluster OT - multinucleated gonocytes OT - testis dysgenesis COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer GH declared a shared affiliation, with no collaboration, with several of the authors, BJ, ZW, CN, QZ, YW, XL, YZ, RG, to the handling editor at the time of review. EDAT- 2021/04/30 06:00 MHDA- 2021/04/30 06:01 PMCR- 2021/04/12 CRDT- 2021/04/29 06:25 PHST- 2020/05/31 00:00 [received] PHST- 2021/02/17 00:00 [accepted] PHST- 2021/04/29 06:25 [entrez] PHST- 2021/04/30 06:00 [pubmed] PHST- 2021/04/30 06:01 [medline] PHST- 2021/04/12 00:00 [pmc-release] AID - 568311 [pii] AID - 10.3389/fphar.2021.568311 [doi] PST - epublish SO - Front Pharmacol. 2021 Apr 12;12:568311. doi: 10.3389/fphar.2021.568311. eCollection 2021.