Deficiency of the onco-miRNA cluster, miR-106bâ¼25, causes oligozoospermia and the cooperative action of miR-106bâ¼25 and miR-17â¼92 is required to maintain male fertility.
Mol Hum Reprod
; 26(6): 389-401, 2020 06 01.
Article
en En
| MEDLINE
| ID: mdl-32330263
ABSTRACT
The identification of new genes involved in sexual development and gonadal function as potential candidates causing male infertility is important for both diagnostic and therapeutic purposes. Deficiency of the onco-miRNA cluster miR-17â¼92 has been shown to disrupt spermatogenesis, whereas mutations in its paralog cluster, miR-106bâ¼25, that is expressed in the same cells, were reported to have no effect on testis development and function. The aim of this work is to determine the role of these two miRNA clusters in spermatogenesis and male fertility. For this, we analyzed miR-106bâ¼25 and miR-17â¼92 single and double mouse mutants and compared them to control mice. We found that miR-106bâ¼25 knock out testes show reduced size, oligozoospermia and altered spermatogenesis. Transcriptomic analysis showed that multiple molecular pathways are deregulated in these mutant testes. Nevertheless, mutant males conserved normal fertility even when early spermatogenesis and other functions were disrupted. In contrast, miR-17â¼92+/-; miR-106bâ¼25-/- double mutants showed severely disrupted testicular histology and significantly reduced fertility. Our results indicate that miR-106bâ¼25 and miR-17â¼92 ensure accurate gene expression levels in the adult testis, keeping them within the required thresholds. They play a crucial role in testis homeostasis and are required to maintain male fertility. Hence, we have identified new candidate genetic factors to be screened in the molecular diagnosis of human males with reproductive disorders. Finally, considering the well-known oncogenic nature of these two clusters and the fact that patients with reduced fertility are more prone to testicular cancer, our results might also help to elucidate the molecular mechanisms linking both pathologies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oligospermia
/
MicroARNs
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Mol Hum Reprod
Asunto de la revista:
BIOLOGIA MOLECULAR
/
MEDICINA REPRODUTIVA
Año:
2020
Tipo del documento:
Article
País de afiliación:
España