4.7 Article

The inhibition of CFTR in the descended testis of SD rats with unilateral cryptorchidism induced by di-(2-ethylhexyl) phthalate (DEHP)

Journal

ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
Volume 29, Issue 51, Pages 77047-77056

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s11356-022-21134-9

Keywords

DEHP; Environmental endocrine disruptors; Unilateral cryptorchidism; Testicular development

Funding

  1. Guangzhou Institute of Pediatrics [YIP-2019-036, GWCMC2020-4-011]
  2. Guangdong Basic and Applied Basic Research Foundation [2020A1515110796]

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DEHP, an environmental endocrine disruptor, may cause serious consequences such as cryptorchidism. This study found that DEHP exposure resulted in abnormal expression of CFTR and its downstream signals in both undescended and descended testis, suggesting that CFTR abnormal expression may contribute to abnormal male reproductive function.
Di-(2-ethylhexyl) phthalate (DEHP) is a kind of environmental endocrine disruptors (EEDs), which has been confirmed to cause serious consequences, such as cryptorchidism. Patients with unilateral cryptorchidism still had oligospermia or infertility even if they received orchidopexy before puberty. Testicular dysgenesis syndrome (TDS) attributes this kind of problems to the abnormal testicular development during the embryonic period, and considers that the environmental exposure factors during pregnancy play a major role. Therefore, for unilateral cryptorchidism, even if one testicle has dropped to scrotum, it may be exposed to these substances and cause damage. Cystic fibrosis transmembrane conduction regulator (CFTR) is very important for the maturation of male reproductive system. Previously, cryptorchidism was thought to cause abnormal expression of heat sensitive protein CFTR in testis, but the expression of CFTR in healthy side (descended side) testis was not clear. In this study, we established SD rats with unilateral cryptorchidism by exposure to DEHP (500 mg/kg/day) during pregnancy, and detected the expression of CFTR and downstream signal NF-kappa B/COX-2/PGE2 in bilateral testis. Finally, we found that the expression of CFTR and downstream signal NF-kappa B/COX-2/PGE2 in the undescended testis was significantly abnormal, but the expression of them in the descended testis was also abnormal to some extent. Therefore, we speculate that in addition to high temperature will affect the expression of CFTR, there may be other factors that cause abnormal expression of CFTR induced by DEHP, and lead to abnormal male reproductive function eventually, but the specific mechanism needs to be further studied.

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