Hodenhochstand – Page 2 – pediatrician.li

Decreased Expression of Genes Associated with Memory and X-Linked Mental Retardation in Boys with Non-Syndromic Cryptorchidism and High Infertility Risk

An elevated odds ratio for low IQ has been found for cryptorchid boys. Furthermore, poor school performance has been observed in cryptorchid boys with impaired mini-puberty.

Gene expression analysis, qPCR and immunohistology wereperformed on testicular biopsies from 7 boys who under-went orchiopexy and had testicular histology typical of ahigh risk of infertility (HIR). The results were compared with12 biopsies from cryptorchid boys with a low risk for develop-ing infertility. The following genes associated with mentalretardation were identically expressed: GDI1, OPHN1, PAK3,ARHGEF6, IL1RAPL, ACSL4, MECP2, RPS6KA3, ARX, and ATRX.However, boys in the HIR group had low or no expression ofEGR4, FMR2 (AFF2) and VCX3A. In conclusion, impaired ex-pression of genes known to encode proteins involved in sig-naling pathways that regulate cytoskeletal organization, syn-aptic vesicle transport and the establishment of connectionsbetween neuronal cells may contribute to reduced intellec-tual and cognitive functioning in infertile cryptorchid males.
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Publikation 'Master Gene'

The purpose of early medical or surgical treatment of boys with undescended testes is to prevent the development ofinf ertility. However, early and successful surgery cannot pre-vent infertility in cryptorchid boys who lack type A dark (Ad) spermatogonia. The aim of this study was to compare the gene expression pattern of patients with completed trans-formation of gonocytes into Ad spermatogonia, associated with low infertility risk, with patients that had failed to un-dergo this process and had a high infertility risk. Genes ex-pressed in the 16 cryptorchid testes were estimated using Affymetrix whole-genome microarray and compared to the expression profiles from four contralateral gonads of boys with unilateral testicular agenesis. Whole-genome expres-sion profiling showed that boys in the high infertility riskgroup according to testicular histology, showed decreasedor lack of expression of most of the genes essential for hypo-thalamo-pituitary-testicular axis function relative to low or intermediate risk group as well as controls. In particular,EGR4, which is involved in regulating the secretion of lutein-izing hormone, was virtually not expressed.
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Publikation Hodenhochstand

Deficient Expression of Genes Involved in the Endogenous Defense System against Transposons in Cryptorchid Boys with Impaired Mini-Puberty.

Mini-puberty is the period between 30 and 80 days after birth when testosterone and gonadotropin surges occur in male infants to induce the transformation of gonocytes into adult/dark spermatogonia. Cryptorchid boys with impaired mini-puberty develop infertility despite timely and success-ful surgical treatment. The decreased germ cell count found in this group of boys could be the result of uncontrolled transposon activity inducing genomic instability and germ cell death. A genome-wide analysis of 18 cryptorchid and 4 control testes was performed with Affymetrix chips. We found that 5 of 8 genes that are important for transposon silencing were not expressed in the high azoospermia risk group of cryptorchid boys but were expressed in the low azoospermia risk and control groups. Two genes, CBX3 and DNMT1, were equally expressed in all 3 groups. Impaired ex-pression of the DDX4, MAEL, MOV10L1, PIWIL2, PIWIL4, and TDRD9 genes in the group of cryptorchid boys at high risk of infertility indicates that gene instability induced by impaired expression of transposon silencing genes contribute to the Cryptorchidism represents one of the most frequent causes of azoospermia in men [Fedder et al., 2004]. Download complete article