AUTHOR=Ji Bin , Wen Zina , Ni Chaobo , Zhu Qiqi , Wang Yiyan , Li Xiaoheng , Zhong Ying , Ge Ren-Shan 

TITLE=The Production of Testosterone and Gene Expression in Neonatal Testes of Rats Exposed to Diisoheptyl Phthalate During Pregnancy is Inhibited

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.568311

DOI=10.3389/fphar.2021.568311

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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 (<italic>Lhcgr</italic>, <italic>Star</italic>, <italic>Cyp11a1</italic>, <italic>Hsd3b1</italic>, <italic>Cyp17a1</italic>, and <italic>Hsd17b3</italic>) and testis descent-related gene (<italic>Insl3</italic>) 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.</p><p><bold>Conclusion:</bold> Gestational exposure to DIHP causes testis dysgenesis in rats.</p>