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Declining levels of miR-382-3p at puberty trigger the onset of spermatogenesis.
Gupta, Alka; Mandal, Kamal; Singh, Parminder; Sarkar, Rajesh; Majumdar, Subeer S.
Afiliação
  • Gupta A; Cellular Endocrinology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
  • Mandal K; Cellular Endocrinology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
  • Singh P; Metabolic Research Laboratory, National Institute of Immunology, New Delhi, India.
  • Sarkar R; Cellular Endocrinology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
  • Majumdar SS; Cellular Endocrinology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Mol Ther Nucleic Acids ; 26: 192-207, 2021 Dec 03.
Article em En | MEDLINE | ID: mdl-34513304
ABSTRACT
A major change in the transcriptome of testicular Sertoli cells (Scs) at the onset of puberty enables them to induce robust spermatogenesis. Through comprehensive literature mining, we generated a list of genes crucial for Sc functioning and computationally predicted the microRNAs regulating them. Differential expression analysis of microRNAs in infant and pubertal rat Scs showed that miR-382-3p levels decline significantly in pubertal Scs. Interestingly, miR-382-3p was found to regulate genes like Ar and Wt1, which are crucial for functional competence of Scs. We generated a transgenic (Tg) mouse model in which pubertal decline of miR-382-3p was prevented by its overexpression in pubertal Scs. Elevated miR-382-3p restricted the functional maturation of Scs at puberty, leading to infertility. Prevention of decline in miR-382-3p expression in pubertal Scs was responsible for defective blood-testis barrier (BTB) formation, severe testicular defects, low epididymal sperm counts and loss of fertility in these mice. This provided substantial evidence that decline in levels of miR-382-3p at puberty is the essential trigger for onset of robust spermatogenesis at puberty. Hence, sustained high levels of miR-382-3p in pubertal Scs could be one of the underlying causes of idiopathic male infertility and should be considered for diagnosis and treatment of infertility.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article