Objectve As an alternatve to environmental endocrine disruptor diethylhexyl phthalate (DEHP), diisodecyl phthalate (DINP) has gradually become one of the most widely used plastcizers. This study aims to explore the effects of embryonic and lactatonal DINP exposure on the reproductve system of male offspring and its possible mechanisms.
Methods In a two-generaton reproducton toxicity study, pregnant Wistar rats were treated with 5, 50, 500, and 1 000 mg/kg (body weight) DINP or corn oil (solvent control) by gavage once a day from gestatonal day 7 (GD7) to postnatal day 21 (PND21), with 5-6 pregnant rats in each group. On PND2, the anogenital distance (AGD) of the pups was measured and the AGD Index was calculated. On PND4, the liters were culled to 8 pups per liter (4 females and 4 males). On PND21 and PND49, 10 male pups randomly selected from each dose group were measured for serum testosterone levels by ELISA and observed for testcular pathological changes. The testis and epididymis coefficients were calculated on PND21, and the mRNA expressions of key genes in testosterone synthesis pathway were determined by real-tme quanttatve PCR.
Results Compared with the solvent control group, the perinatal loss and male-female sex rato of the newborn rats in the designed DINP groups were not statstcally different (P>0.05), but the AGDs of male pups were signifcantly shortened to (5.15±0.37), (5.17±0.33), (4.57±0.38), and (5.16±0.32) mm in the order of low to high DINP exposure level, respectvely, and the AGD indices of the 500 and 1 000mg/kg dose groups were signifcantly reduced to (2.48±0.19) and (2.51±0.13), respectvely. Compared with the control group, on PND21, the mRNA expression levels of Star were signifcantly increased in the DINP-treated groups at 50 mg/kg and above, the levels of Scarb1 were signifcantly decreased in the DINP-treated groups at 500 and 1 000 mg/kg, and the levels of Lhcgr was signifcantly reduced in the 1 000 mg/kg DINP-treated group (P < 0.05). The spermatogenic cells and spermatozoa decreased and aggregaton appeared in the intersttal cells afer the DINP treatment on PND49; but there was no signifcant decrease in serum testosterone concentratons in the male rats on PND21 and PND49 (P>0.05).
Conclusion Embryonic and lactatonal DINP exposure affects the reproductve system of male F1 rats. Scarb1, Star and Lhcgr, key genes of testosterone synthesis, may play a role in the male reproductve toxicity of DINP.
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