Abstract

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. Using RNA-sequencing of testicular biopsies, we recently examined RNA profiles of testes with and without GnRHa treatment. Here, we focused on the expression patterns of known gene markers for gonocytes and spermatogonia, and found that DMRTC2, PAX7, BRACHYURY/T, and TERT were associated with defective mini-puberty and were responsive to GnRHa. These results indicate novel testosterone-dependent genes and provide valuable insight into the transcriptional response to both defective mini-puberty and curative GnRHa treatment, which prevents infertility in man with one or both undescended (cryptorchid) testes.

Highlights

  • During mini-puberty, which occurs between 30 and 90 days of postnatal life in male infants, the substantial increase in gonadotropin releasing hormone (GnRH) secretion induces gonadotropin and testosterone production [1,2,3]

  • We focused on selected marker genes for gonocytes and adult dark (Ad) spermatogonia (Table 1)

  • The reduced levels of POU5F1 and TFAP2C RNA, observed in Ad− testes compared to Ad+ testes, lead to the assumption that they play an important role in luteinizing hormone (LH) and in the testosterone-dependent gonocyte-to-Ad spermatogonia transition

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Summary

Introduction

During mini-puberty, which occurs between 30 and 90 days of postnatal life in male infants, the substantial increase in gonadotropin releasing hormone (GnRH) secretion induces gonadotropin and testosterone production [1,2,3]. Transformation of gonocytes into adult dark (Ad) spermatogonia takes place. Ad spermatogonia have a characteristic nuclear feature that distinguishes them from the other germ cells (e.g., fetal, transient, and pale-type (Ap) spermatogonia)

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