Abnormal germ cell development in cryptorchidism is not a result of a congenital dysgenesis but is preceded by a hormone imbalance and perturbation in germ cell-specific gene expression during abrogated mini-puberty.Adequate treatment with low doses of GnRHa enables 86% of men to achieve a normal sperm count and, most importantly, prevent development of azoospermia. GnRHa treatment induces a significant transcriptional response, including protein coding genes involved in pituitary development, the hypothalamic-pituitary-gonadal axis, and testosterone synthesis. Furthermore, hormonal treatment to achieve epididymo-testicular descent as a first choice of treatment of cryptorchidism has a long tradition in Europe. It eliminates the necessity of subsequent surgery. Moreover, in the cases of non-responders it facilitates orchidopexy and contributes considerably to a reduced incidence of unilateral and the more serious bilateral complete post-surgical testicular atrophy.
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DMRTC2, PAX7, BRACHYURY/T and TERT Are Implicated in Male Germ Cell Development Following Curative Hormone Treatment for Cryptorchidism-Induced Infertility
Defective mini-puberty results in insufficient testosterone secretion that impairs the differentiation of gonocytes into dark-type (Ad) spermatogonia. The differentiation of gonocytes into Ad spermatogonia can be induced by administration of the gonadotropin-releasing hormone agonist, GnRHa (Buserelin, INN)). Nothing is known about the mechanism that underlies successful GnRHa treatment in the germ cells.
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Gene Expression Changes Underlying Idiopathic Central Hypogonadism in Cryptorchidism with Defective Mini-Puberty
Gene Expression Changes Underlying Idiopathic Central Hypogonadism in Cryptorchidism with Defective Mini-Puberty
The whole genome RNA profiling of testicular biopsies by DNA strand-specific RNA sequencing was examined to determine a potential causative role of isolated congenitalcryptorchidism 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.
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