A novel role for CFTR interaction with LH and FGF in azoospermia and epididymal maldevelopment caused by cryptorchidism

AbstractCryptorchidism occurs frequently in children with cystic fibrosis. Among boys with cryptorchidism and abrogated mini-puberty, the development of the epididymis and the vas deferens is frequently impaired. This finding suggests that a common cause underlies the abnormal development of Ad spermatogonia and the epididymis. The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette transporter protein that acts as a chloride channel. TheCFTR gene has been associated with spermatogenesis and male fertility. In boys with cryptorchidism, prepubertal hypogonadotropic hypogonadism induces suboptimal expression of the ankyrin-like protein gene,ASZ1, the P-element induced wimpy testis-like gene,PIWIL, andCFTR. The abrogated expression of these gene leads to transposon reactivation, and ultimately, infertility. Curative gonadotropin-releasing hormone agonist (GnRHa) treatment stimulates the expression ofCFTR andPIWIL3, which play important roles in the development of Ad spermatogonia and fertility. Furthermore, GnRHa stimulates the expression of the epididymal androgen-sensitive genes,CRISP1, WFDC8, SPINK13, andPAX2, which thereby promotes epididymal development. This review focuses on molecular evidence that favors a role forCFTR in cryptorchidism-induced infertility. Based on information available in the literature, we interpreted our RNA-Seq expression data obtained from samples before and after randomized GnRHa treatment in boys with bilateral c...
Source: Basic and Clinical Andrology - Category: Urology & Nephrology Source Type: research