Genetic Deficiency of Mtdh Gene in Mice Causes Male Infertility via Impaired Spermatogenesis and Alterations in the Expression of Small Non-coding RNAs

Meng, Xiangjun; Yang, Shujie; Zhang, Yuping; Wang, Xinjun; Goodfellow, Renee X.; Jia, Yichen; Thiel, Kristina W.; Pineda, Henry Reyes; Yang, Baoli; Leslie, Kimberly K.

doi:10.1074/jbc.m114.627653

Cited by 20 publications

(14 citation statements)

References 39 publications

(54 reference statements)

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“…anti-H3K4me2 rabbit polyclonal 1/500 Millipore (07-030) [13][14][15] anti-H3K4me3 rabbit polyclonal 1/500 Abcam (ab8580) [16][17][18] anti-H3K9me3 rabbit polyclonal 1/500 Abcam (ab8898) [19][20][21] anti-H3K27ac rabbit polyclonal 1/500 Abcam (ab4729) [22][23][24] anti-H3K27me2 rabbit polyclonal 1/500 Abcam (ab24684) [25,26] anti-H3K27me3 rabbit polyclonal 1/500 Millipore (07-449) [24,[27][28][29] anti-H3K79me2 rabbit polyclonal 1/500 Abcam (ab3594) [30][31][32] anti-H3K79me3 rabbit polyclonal 1/500 Abcam (ab2621) [33][34][35] anti-SCP3 mouse monoclonal 1/500 Abcam (ab97672) [36][37][38] anti-α-Tubulin (S2 Fig) mouse monoclonal 1/500 Sigma-Aldrich (T6199) [39,40] All antibodies are commercially available, and their specificity has been reported in previous studies.…”

Section: Antibody Name Source Dilution Company (Catalogue) Referencementioning

confidence: 99%

Comprehensive histochemical profiles of histone modification in male germline cells during meiosis and spermiogenesis: Comparison of young and aged testes in mice

et al. 2020

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Human epidemiological studies have shown that paternal aging as one of the risk factors for neurodevelopmental disorders, such as autism, in offspring. A recent study has suggested that factors other than de novo mutations due to aging can influence the biology of offspring. Here, we focused on epigenetic alterations in sperm that can influence developmental programs in offspring. In this study, we qualitatively and semiquantitatively evaluated histone modification patterns in male germline cells throughout spermatogenesis based on immunostaining of testes taken from young (3 months old) and aged (12 months old) mice. Although localization patterns were not obviously changed between young and aged testes, some histone modification showed differences in their intensity. Among histone modifications that repress gene expression, histone H3 lysine 9 trimethylation (H3K9me3) was decreased in the male germline cells of the aged testis, while H3K27me2/3 was increased. The intensity of H3K27 acetylation (ac), an active mark, was lower/higher depending on the stages in the aged testis. Interestingly, H3K27ac was detected on the putative sex chromosomes of round spermatids, while other chromosomes were occupied by a repressive mark, H3K27me3. Among other histone modifications that activate gene expression, H3K4me2 was drastically decreased in the male germline cells of the aged testis. In contrast, H3K79me3 was increased in M-phase spermatocytes, where it accumulates on the sex chromosomes. Therefore, aging induced alterations in the amount of histone modifications and in the differences of patterns for each modification. Moreover, histone modifications on the sex chromosomes and on other chromosomes seems to be differentially regulated by aging. These findings will help elucidate the epigenetic mechanisms underlying the influence of paternal aging on offspring development.

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Section: Antibody Name Source Dilution Company (Catalogue) Referencementioning

confidence: 99%

Comprehensive histochemical profiles of histone modification in male germline cells during meiosis and spermiogenesis: Comparison of young and aged testes in mice

et al. 2020

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“…Recently, altered expression levels of some miRNAs have also been correlated with the extent of sperm DNA damage observed in male infertility. In an infertile knock-out mouse model, increase in unrepaired DNA breaks has been linked with reduced expression of miR-16 and miR-19b in testes [131]. Moreover, analysis of seminal plasmas from 94 infertile men with high sperm DNA fragmentation index has revealed significant downregulation of miR-424 in this group, implicating a role for miR-424 in repair of double-strand breaks during spermatogenesis [111].…”

Section: Seminal Fluidal Mirnas and Male Infertilitymentioning

confidence: 97%

The role of epigenetics in idiopathic male infertility

Güneş

Arslan

Hekim

et al. 2016

J Assist Reprod Genet

106

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Infertility is a complex disorder with multiple genetic and environmental causes. Although some specific mutations have been identified, other factors responsible for sperm defects remain largely unknown. Despite considerable efforts to identify the pathophysiology of the disease, we cannot explain the underlying mechanisms of approximately half of infertility cases. This study reviews current data on epigenetic regulation and idiopathic male infertility. Recent data have shown an association between epigenetic modifications and idiopathic infertility. In this regard, epigenetics has emerged as one of the promising research areas in understanding male infertility. Many studies have indicated that epigenetic modifications, including DNA methylation in imprinted and developmental genes, histone tail modifications and short non-coding RNAs in spermatozoa may have a role in idiopathic male infertility.

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“…Male infertility may have a variety of causes, including azoospermia, oligospermia, asthenospermia, orchitis, and varicocele (Esteves & Agarwal, 2016;Wu et al, 2016). The pathogenesis of the male diseases listed above is usually derived from two factors: a genetic factor (Liu et al, 2015;Meng et al, 2015) and an environmental factor. The latter includes oxidative stress and heat stress (Darr et al, 2016;Reyes et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia‐induced apoptosis of mouse spermatocytes is mediated by HIF‐1α through a death receptor pathway and a mitochondrial pathway

Yin

Liao

et al. 2017

Journal Cellular Physiology

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Hypoxia in vivo induces oligozoospermia, azoospermia, and degeneration of the germinal epithelium, but the underlying molecular mechanism of this induction is not fully clarified. The aim of this study was to investigate the role of the death receptor pathway and the mitochondrial pathway in hypoxia-induced apoptosis of mouse GC-2spd (GC-2) cells and the relationship between HIF-1α and apoptosis of GC-2 cells induced by hypoxia. GC-2 cells were subjected to 1% oxygen for 48 hr. Apoptosis was detected by flow cytometry, TUNEL staining, LDH, caspase-3/8/9 in the absence and presence of HIF-1α siRNA. The protein levels of apoptosis-related markers were determined by Western blot in the presence and absence of HIF-1α siRNA. Mitochondrial transmembrane potential change was observed by in situ JC-1 staining. Cell viability was assessed upon treatment of caspase-8 and 9 inhibitors. The results indicated that hypoxia at 1% oxygen for 48 hr induced apoptosis of GC-2 cells. A prolonged exposure of GC-2 cells to hypoxic conditions caused downregulation of c-FLIP, D R and Bcl-2 and upregulation of DR , TRAIL, Fas, p53, and Bax, with an overproduction of caspase-3/8/9. Moreover, hypoxia at this level had an effect on mitochondrial depolarization. In addition, specific inhibitors of caspase-8/9 partially suppressed hypoxia-induced GC-2 cell apoptosis, and the anti-apoptotic effects of the caspase inhibitors were additive. Of note, HIF-1α knockdown attenuated hypoxia and induced apoptosis of GC-2 cells. In conclusion, our data suggest that the death receptor pathway and mitochondrial pathway, which are likely mediated by HIF-1α, contribute to hypoxia-induced GC-2 cell apoptosis.

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Genetic Deficiency of Mtdh Gene in Mice Causes Male Infertility via Impaired Spermatogenesis and Alterations in the Expression of Small Non-coding RNAs

Cited by 20 publications

References 39 publications

Comprehensive histochemical profiles of histone modification in male germline cells during meiosis and spermiogenesis: Comparison of young and aged testes in mice

Comprehensive histochemical profiles of histone modification in male germline cells during meiosis and spermiogenesis: Comparison of young and aged testes in mice

The role of epigenetics in idiopathic male infertility

Hypoxia‐induced apoptosis of mouse spermatocytes is mediated by HIF‐1α through a death receptor pathway and a mitochondrial pathway

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