Endoplasmic reticulum stress, a novel significant mechanism responsible for DEHP-induced increased distance between seminiferous tubule of mouse testis.

Di(2-ethylhexyl) phthalate (DEHP), a widely existed endocrine disruptor, has been concerned for many years owing to its toxicity in male reproductive development. In this study, we investigated the reproductive effects and the mechanism of mouse testis after in uterus exposure to the plasticizer DEHP. We found that the UPR signaling pathway could be fully activated after DEHP treatment. In uterus DEHP exposure significantly increased abnormal morphology seminiferous tubules, expanded the distance between the tubules as well as caused abnormal endoplasmic reticulum (ER) ultrastructure, which could be reversed by 4-phenylbutyrate (4-PBA), an ER stress inhibitor. In addition, DEHP-induced ER stress pathway promoted a decline in protein expression, including cadherin protein N-cadherin in testis, which could also be reversed by 4-PBA. Taken together, our results provide compelling evidence that the ER stress would be a novel significant mechanism responsible for DEHP-induced the increased the distance between seminiferous tubule by reducing the N-cadherin expression.