Inutero exposure to diisononyl phthalate caused testicular dysgenesis of rat fetal testis.
Diisononyl phthalate (DINP) is a synthetic material that has been widely used as a substitute for other plasticizers prohibited due to reproductive toxicity in consumer products. Some phthalates have been associated with testicular dysgenesis syndrome in male fetus when female pregnant dams were exposed to them. The present study investigated effects of DINP on fetal Leydig cell function and testis development. Female pregnant Sprague Dawley rats received control vehicle (corn oil) or DINP (10, 100, 500, and 1000 mg/kg) by oral gavage from gestational day (GD) 12 to 21. At GD 21.5, testicular testosterone production, fetal Leydig cell numbers and distribution, testicular gene and protein expression levels were examined. DINP showed dose-dependent increase of fetal Leydig cell aggregation with the low observed adverse-effect level (LOAEL) of 10 mg/kg and multinucleated gonocyte with LOAEL of 100 mg/kg. At 10 mg/kg, DINP also significantly increased fetal Leydig cell size, but inhibited insulin-like 3 and 3β-hydroxysteroid dehydrogenase gene expression and protein levels. DINP inhibited testicular testosterone levels at 1000 mg/kg. The results indicate that in utero exposure to DINP affects the expression levels of some fetal Leydig cell steroidogenic genes, gonocyte multinucleation and Leydig cell aggregation.
['Li|Linxi|L|', 'Bu|Tiao|T|', 'Su|Huina|H|', 'Chen|Zhichuan|Z|', 'Liang|Yuyuan|Y|', 'Zhang|Gaolong|G|', 'Zhu|Danyan|D|', 'Shan|Yuanyuan|Y|', 'Xu|Renai|R|', 'Hu|Yuanyuan|Y|', 'Li|Junwei|J|', 'Hu|Guoxin|G|', 'Lian|Qingquan|Q|', 'Ge|Ren-Shan|RS|']
D015096:3-Hydroxysteroid Dehydrogenases D000818:Animals D003893:Desmin D005260:Female D015870:Gene Expression D006059:Gonadal Dysgenesis D007985:Leydig Cells D008297:Male D010795:Phthalic Acids D010968:Plasticizers D011247:Pregnancy D051381:Rats D017207:Rats, Sprague-Dawley D013737:Testis D013739:Testosterone
Diisononyl phthalate Testicular dysgenesis Fetal Leydig cell Leydig cell aggregation Gonocyte multinucleation