Phthalate Exposure During Pregnancy and Lactation Transgenerationally Impairs the Epididymis in the Offspring of Rats

Phthalates are chemical compounds used as plasticizers in plastic products, for guaranteeing their flexibility. These compounds damage the epididymal morphophysiology. This study aimed to verify the changes in the epididymis of neonatal and adult rats over two generations. Pregnant Sprague-Dawley females were divided into four groups and gavaged daily from GD10 to PND21 with corn oil (Control:C) or the phthalate mixture at three doses (20, 200, and 200 mg/Kg). F1 animals were euthanized at 22PND and 120PND; unexposed females were mated with 90PND males to obtain the F2 generation. Male rats were euthanized at 22PND. Tissue remodeling of the compartments was observed at all doses in the 22PND animals of both generations. Treatment at 200 mg/Kg resulted in alterations, a decrease in the epithelium and a consequent increase in the lumen in the cauda in F1 PND22. The lumen in the caput and cauda increased, with a reduction in the interstitium at 200 mg/Kg in F2 PND22. The lumen diameter was reduced in the caput and increased in the interstitium at the two highest doses in adult animals. The expression of GPR30, GPX3, GSR, IL10, and TNFa was reduced in adult animals at the highest dose. GPR30 expression increased at 200 mg/Kg dose in PND22. TNFa expression was reduced at all doses in F1 PND22 animals and significantly increased in F2 PND22 animals at 200 µg/Kg and 200 mg/Kg doses. In conclusion, phthalates modify the epididymal structure and impair gene expression, mainly in the late phase.