ESPE Abstracts

Aim of the Study: Cryptorchidism occurs more frequently in CF-children, and malformed epididymis was found more in cryptorchid boys with abrogated mini-puberty. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is transporter protein that acts as a chloride channel. Specifically, CFTR is associated with spermatogenesis and fertility.

Patients and Methods: Testicular biopsies for histological and RNA analysis from bilateral cryptorchid boys were analyzed. RiboMinus Gold/TrueSeq (Illumina) RNA protocol was utilized. No Ad spermatogonia identified high infertility risk patients who were randomized for treatment either with surgery and GnRHa or surgery only.

Main results: In cryptorchid boys, hypogonadotropic hypogonadism induces the reactivation of transposons and suboptimal expression of ASZ1, PIWIL genes and CFTR. (Table 1) Curative GnRHa treatment stimulates expression of CFTR and PIWIL3 genes which are important for the development of Ad spermatogonia and subsequent fertility.(Table 2) Furthermore, GnRHa stimulates the expression of androgen sensitive epidydimal genes: CRISP1, WFDC8, SPINK13, PAX2. The high incidence of abnormal epididymis in HIR patients may stem from a combination of hypogonadotropic hypogonadism and insufficient CFTR activity.

Conclusions: Novel observation is that in cryptorchid boys CFTR is controlled by LH and testosterone influencing activities of genes that are important for fertility and the differentiation of the Wolffian duct.