GnRHa Treatment of Cryptorchid Boys Affects Genes Involved in Hormonal Control of the HPG Axis and Fertility

Sex Dev. 2017;11(3):126-136. doi: 10.1159/000471937. Epub 2017 May 16.

Abstract

The gonadotropin-releasing hormone agonist (GnRHa; Buserelin) rescues fertility during adulthood in the majority of high infertility risk cryptorchid boys presenting with defective mini-puberty. However, the molecular events governing this effect are not understood. We report the outcome of an RNA profiling analysis of testicular biopsies from 4 operated patients who were treated with GnRHa for 6 months versus 3 operated controls who were not treated. GnRHa induces a significant transcriptional response, including protein-coding genes involved in pituitary development, the hypothalamic-pituitary-gonadal axis, and testosterone synthesis. Furthermore, we observed an increased abundance of long noncoding RNAs (lncRNAs) participating in epigenetic processes, including AIRN, FENDRR, XIST, and HOTAIR. These data are consistent with the hypothesis that hypogonadotropic hypogonadism in boys with altered mini-puberty is the consequence of a profoundly altered gene expression program involving protein-coding genes and lncRNAs. Our results point to molecular mechanisms that underlie the ability of GnRHa to rescue fertility.

Keywords: Cryptorchidism; GnRHa treatment; Infertility; RNA sequencing.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Cryptorchidism / drug therapy*
  • Cryptorchidism / genetics*
  • Cryptorchidism / surgery
  • Fertility / drug effects
  • Fertility / genetics*
  • Gene Expression Regulation / drug effects
  • Gonadotropin-Releasing Hormone / pharmacology
  • Gonadotropin-Releasing Hormone / therapeutic use*
  • Humans
  • Hypothalamo-Hypophyseal System / pathology*
  • Infant
  • Male
  • Pituitary Gland / drug effects
  • Pituitary Gland / growth & development
  • Protein Interaction Maps / drug effects
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • Testosterone / biosynthesis
  • Testosterone / metabolism*

Substances

  • RNA, Long Noncoding
  • Gonadotropin-Releasing Hormone
  • Testosterone