Abstract
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.
Highlights
Diisoheptyl phthalate (DIHP, CAS number 71888–89–6) is a synthetic phthalate plasticizer
From the 12th to the 21st day of gestation (GD), the female rats were gavaged with DIHP with 0, 10, 100, 500 or 1,000 mg/kg bodyweight every day (Supplementary Figure S1)
Further research has shown that DIHP induced abnormal fetal Leydig cell aggregation and down-regulated the expression of genes related to steroid production (Lhcgr, steroidogenic acute regulatory protein (Star), Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3) and earlier testis descent (Insl3) and growth factor secreted by Sertoli cells (Dhh)
Summary
Diisoheptyl phthalate (DIHP, CAS number 71888–89–6) is a synthetic phthalate plasticizer. It is an ester formed by one molecule of phthalic acid and two molecules of branched carbon chain alcohol. It belongs to a branched phthalate ester with six carbon atoms in the carbon backbone (Supplementary Figure S1). DIHP may exist in lubricating oil (ECHA, 2011). There are no data on the absorption, distribution, metabolism, and excretion of DIHP in animal models and humans (ECHA, 2011), like other phthalates in the human body, DIHP may be rapidly converted to monoortho phthalate metabolites by lipase (Holm et al, 2004). Diisoheptyl phthalate (DIHP) is a phthalate plasticizer, which is a branched phthalate. We reported the effects of gestational exposure to DIHP on testis development in male rats
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