Open AccessReduced micro RNA ‐188‐3p expression contributes to apoptosis of spermatogenic cells in patients with azoospermia
Author(s) -
Song WenYan,
Meng Hui,
Wang XueGai,
Jin HaiXia,
Yao GuiDong,
Shi SenLin,
Wu Liang,
Zhang XiangYang,
Sun YingPu
Publication year - 2017
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12297
Subject(s) - azoospermia , obstructive azoospermia , chromatin immunoprecipitation , biology , andrology , mlh1 , cancer research , spermatogenesis , apoptosis , histone , blot , microbiology and biotechnology , gene expression , medicine , dna mismatch repair , dna repair , gene , promoter , genetics , infertility , pregnancy
Background and aims Human mutL homologl ( MLH 1) works coordinately in sequential steps to initiate repair of DNA mismatches, and aberrant MLH 1 expression is related to spermatogenetic malfunction. In the present study, MLH 1 expression in patients with azoospermia was investigated, and moderating effects of miR‐188‐3p on MLH 1 expression and spermatogenesis were identified. Methods Testicular tissues from 16 patients with obstructive azoospermia ( OA ) and non‐obstructive azoospermia ( NOA ), and tissues of eight healthy patients were collected. Real‐time PCR , Western blotting and immunohistochemical staining were used to detect MLH 1 expression. Chromatin immunoprecipitation assay and luciferase reporter assay were performed to evaluate histone acetylation level of miR‐188‐3p and relationships between miR‐188‐3p and MLH 1. Results Testicular MLH 1 expression at mRNA and protein levels was significantly increased, while miR‐188‐3p expression was lower in patients with OA and NOA than that in controls. Reduced histone acetylation level of miR‐188‐3p promoter was observed in patients with azoospermia. Overexpression/inhibition of HDAC 1, but not HDAC 2, contributed to the significant reduction/increase of miR‐188‐3p expression. miR‐188‐3p targeted 3′ UTR of MLH 1 and regulated MLH 1 expression. miR‐188‐3p inhibitor led to elevation of apoptotic level of spermatogenic cells in mice, while this effect was reversed by si‐ MLH 1. Conclusion Down‐regulation of miR‐188‐3p by reducing histone acetylation up‐regulated MLH 1 expression and contributed to promotion of apoptosis in spermatogenic cells, in patients with azoospermia.