title: Piwi-pathway alteration induces LINE-1 transposon derepression and infertility development in cryptorchidism.
abstract: Spermatogonia contain processing bodies that harbor P-element-induced wimpy testis (Piwi) proteins. Piwi proteins are associated specifically with Piwi-interacting RNAs to silence transposable DNA elements. Loss-of-function mutations in the Piwi pathway lead to derepression of transposable elements, resulting in defective spermatogenesis. Furthermore, deletion of gametocyte-specific factor 1 (GTSF1), a factor involved in Piwi-mediated transcriptional repression, causes male-specific sterility and derepression of LINE-1 (L1) retrotransposons. No previous studies have examined GTSF1, L1 and PIWIL4 expression in cryptorchidism. We examined transposon-silencing genes and L1 transposon expression in testicular biopsies with Affymetrix microarrays and immunohistology. Seven members of the Tudor gene family, 3 members of the DEAD-box RNA helicase family, and the GTSF1 gene were found to show significantly lower RNA signals in the high-infertility-risk group. In the immunohistochemical analysis, patients from the low-infertility-risk group showed coherently stronger staining for GTSF1 and PIWIL4 proteins and weaker staining for L1 transposon when compared to the high-infertility-risk samples. These new findings provide first evidence consistent with the idea that infertility in cryptorchidism is a consequence of alterations in the Piwi pathway and transposon derepression induced by the impaired function of mini-puberty.
authors: Institute for Andrology, Liestal, Switzerland.
authors: Faruk
authors: F
authors: Hadziselimovic
authors: Nils O
authors: NO
authors: Hadziselimovic
authors: Philippe
authors: P
authors: Demougin
authors: Gunthild
authors: G
authors: Krey
authors: Eduard
authors: E
authors: Oakeley
mesh_terms: D002675:Child, Preschool; D003456:Cryptorchidism / Q000150:complications / Q000235:genetics*; D004251:DNA Transposable Elements / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D007248:Infertility, Male / Q000150:complications / Q000235:genetics*; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D012307:Risk Factors; D013094:Spermatozoa / Q000648:ultrastructure
chemical_list: D004251:DNA Transposable Elements; D012333:RNA, Messenger; D034741:RNA, Small Interfering