Objective and hypotheses: The objective was to use whole-genome RNA profiling of testicular biopsies by DNA strand-specific RNA-sequencing to explore the causative role of isolated congenital cryptorchidism in azoospermia and/or infertility.
Method: Fifteen cryptorchid patients, aged 7 months to 5 years, were enrolled in this study and underwent orchidopexy. During surgery, testicular tissue biopsies were collected and split in half for histological examination and RNA-seq.
Results: Our RNA profiling data strongly supports the theory that idiopathic central hypogonadism induces impaired mini-puberty, resulting in azoospermia and/or infertility. The identification of multiple differences in gene expression between high and low-infertility risk groups further underscores the importance of an intact hypothalamic-pituitary-gonadal axis for fertility development. GnRH receptor expression is likewise regulated by Msx1, Dlx2, and Dlx3 in mice. Further mediators of GnRH receptor gene expression have been reported and include Sf1, Nr4a1/Nur77, Lhx3, Six3, and Six6. In our expression study, the MSX1, DLX2, DLX3, NR4A1, and LHX3 genes were decreased in the high infertility risk group.
Conclusion: Our finding of insufficiently expressed genes directly involved in the modulation of αGSU and LHβ expression implies a direct effect on LH production and provides a plausible explanation for the reduced LH levels measured in HIR patients. Furthermore, our molecular data supports the hypothesis of insufficient PROK2 gene expression participating in induction of luteinizing hormone deficiency, with EGR4/PITX1 as gene controller.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology