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.
Subject(s)
Cryptorchidism/metabolism , Hypogonadism/metabolism , Hypogonadism/physiopathology , Puberty/physiology , Azoospermia/genetics , Azoospermia/metabolism , Azoospermia/physiopathology , Child, Preschool , Cryptorchidism/genetics , Cryptorchidism/physiopathology , DNA Helicases/genetics , DNA Helicases/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Gastrointestinal Hormones/genetics , Gastrointestinal Hormones/metabolism , Humans , Hypogonadism/genetics , Infant , Infertility, Male/genetics , Infertility, Male/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Male , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neuropeptides/genetics , Neuropeptides/metabolism , Prospective Studies , Puberty/genetics , Receptor, Fibroblast Growth Factor, Type 1/genetics , Receptor, Fibroblast Growth Factor, Type 1/metabolism , Spermatogonia/metabolism , Spermatogonia/physiologyABSTRACT
In Huntington's disease (HD), the distribution of pathological changes throughout the brain is incompletely understood. Some studies have identified leftward-biased lateralization, whereas others did not. We performed magnetic resonance imaging and a voxel-based asymmetry analysis in 44 right-handed HD gene carriers (presymptomatic, n = 5; stage I, n = 28; stage II, n = 11) and 44 right-handed healthy controls. The group comparison revealed leftward-biased gray matter loss in the striatum. Further analyses showed no indication of asymmetry in presymptomatic HD patients but an increase in asymmetry in the course of the HD stages under examination. Our study demonstrates and discusses leftward-biased gray matter loss in HD.
