Inherited defects of piRNA biogenesis cause transposon de-repression, impaired spermatogenesis, and human male infertility.
Nat Commun
; 15(1): 6637, 2024 Aug 09.
Article
em En
| MEDLINE
| ID: mdl-39122675
ABSTRACT
piRNAs are crucial for transposon silencing, germ cell maturation, and fertility in male mice. Here, we report on the genetic landscape of piRNA dysfunction in humans and present 39 infertile men carrying biallelic variants in 14 different piRNA pathway genes, including PIWIL1, GTSF1, GPAT2, MAEL, TDRD1, and DDX4. In some affected men, the testicular phenotypes differ from those of the respective knockout mice and range from complete germ cell loss to the production of a few morphologically abnormal sperm. A reduced number of pachytene piRNAs was detected in the testicular tissue of variant carriers, demonstrating impaired piRNA biogenesis. Furthermore, LINE1 expression in spermatogonia links impaired piRNA biogenesis to transposon de-silencing and serves to classify variants as functionally relevant. These results establish the disrupted piRNA pathway as a major cause of human spermatogenic failure and provide insights into transposon silencing in human male germ cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espermatogênese
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Testículo
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Elementos de DNA Transponíveis
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RNA Interferente Pequeno
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Infertilidade Masculina
Limite:
Adult
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Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article