title: Gene Expression Changes Underlying Idiopathic Central Hypogonadism in Cryptorchidism with Defective Mini-Puberty.
abstract: The whole genome RNA profiling of testicular biopsies by DNA strand-specific RNA sequencing was examined to determine a potential causative role of isolated congenital cryptorchidism in azoospermia and/or infertility in the context of our previously published GeneChip data. Cryptorchid patients, aged 7 months to 5 years and otherwise healthy, were enrolled in this prospective study. During surgery, testicular tissue biopsies were obtained for histological examination and RNA sequencing. Fifteen patients were selected based on the histological results and were divided into 2 groups. Seven were classified as belonging to the high infertility risk (HIR) and 8 to the low infertility risk (LIR) group. Cryptorchid boys in the HIR group lacked transformation of gonocytes into Ad spermatogonia due to impaired mini-puberty. This group of patients will be infertile despite successful surgery. The new important finding was a decreased PROK2, CHD7, FGFR1, and SPRY4 gene expression in the HIR group. Furthermore, identification of multiple differences in gene expression between HIR and LIR groups underscores the importance of an intact hypothalamic-pituitary-gonadal axis for fertility development. Our RNA profiling data strongly support the theory that in the HIR group of cryptorchid boys insufficient PROK2/CHD7/FGFR1/SPRY4 gene expression induces deficient LH secretion, resulting in impaired mini-puberty and infertility. We therefore recommend hormonal treatment for this cohort of cryptorchid boys with defective mini-puberty following a seemingly successful orchidopexy.
authors: Faruk
authors: F
authors: Hadziselimovic
authors: Katharina
authors: K
authors: Gegenschatz-Schmid
authors: Gilvydas
authors: G
authors: Verkauskas
authors: Maria J
authors: MJ
authors: Docampo-Garcia
authors: Philippe
authors: P
authors: Demougin
authors: Vytautas
authors: V
authors: Bilius
authors: Dalius
authors: D
authors: Malcius
authors: Darius
authors: D
authors: Dasevicius
authors: Michael B
authors: MB
authors: Stadtler
mesh_terms: D053713:Azoospermia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D002675:Child, Preschool; D003456:Cryptorchidism / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005768:Gastrointestinal Hormones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007006:Hypogonadism / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D007223:Infant; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D011446:Prospective Studies; D011627:Puberty / Q000235:genetics / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism; D013093:Spermatogonia / Q000378:metabolism / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D005768:Gastrointestinal Hormones; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C423608:PROK2 protein, human; C499038:SPRY4 protein, human; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D004265:DNA Helicases; C491434:CHD7 protein, human