Background: Spermatogonia contain processing bodies (P-bodies) that harbour P-element induced wimpy testis (Piwi) proteins associated specifically with Piwi-interacting RNAs to silence transposable DNA elements. In mice loss-of-function mutations in the Piwi pathway lead to de-repression of transposable elements, resulting in male-specific sterility.
Objective and hypotheses: No previous studies have examined expression of transposons silencing gene microchidia 1 (MORC1) in cryptorchidism.
Method: For microarray analysis we included 19 rice-grain-sized testicular biopsies. High infertility risk group (HIR, n=7) is defined as a lack of Ad spermatogonia due to impaired mini-puberty while low infertility risk group (LIR, n=12) is defined as ≥0.1 Ad spermatogonia per tubular cross section and intact mini-puberty.
Results: Conserved epigenetic regulator gene MORC1 an important repressor of transposons acting by facilitating DNA methylation of specific repetitive elements classes, was not expressed in HIR; 3.49 log2 in contrast to robust expression in LIR; 5.26 log2 (P<0.004).The HIR group showed stronger L1 staining in the cytoplasm of the germ cells. In contrast, ASZ1 testis specific transposon silencing gene was not expressed in the high infertility risk group, and it was not detected in four out of seven LIR testes. Three boys in the LIR group showed ASZ1 expression. Their testes had spermatocytes. Therefore, ASZ1 expression in prepubertal testes appeared to be correlated to the existence of spermatocytes.
Conclusions: This observation further supports our very recent finding that seven members of the TDRD family, three members of DDX family and GTSF1 gene had significantly lower RNA signals in high infertility risk group. Although both LIR and HIR groups contained GTSF1, L1, and PIWIL4 proteins in the germ cells, the HIR group showed weaker GTSF1 and PIWIL4 expression and stronger L1 staining. Furthermore, these new findings provide strong evidence that infertility in cryptorchidism is a consequence of alterations in the Piwi-pathway. MORC1 participates down-stream of the piRNA pathway with a separate silencing role. Moreover, this novel observation implies that the growth and formation of P-bodies are hormonally regulated during mini-puberty, and that, during that time, P-bodies contribute to the establishment of germ cell memory and male-specific DNA methylation pathways. Intact mini-puberty appears to be essential for the development of the endogenous defence system. mediated by transposon.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology