Testosterone-Dependent miR-26a-5p and let-7g-5p Act as Signaling Mediators to Regulate Sperm Apoptosis via Targeting PTEN and PMAIP1

Ma, Jideng; Fan, Yu; Zhang, Jinwei; Feng, Siyuan; Hu, Zihui; Qiu, Wanling; Long, Keren; Jin, Long; Tang, Qianzi; Wang, Xun; Zhou, Qi; Gu, Yiren; Xiao, Weihang; Liu, Lingyan; Li, Xuewei; Li, Mingzhou

doi:10.3390/ijms19041233

Cited by 43 publications

(26 citation statements)

References 71 publications

(77 reference statements)

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“…Interestingly the results from that study have shown 47%-52% of the miRNAs that has been detected in the wild type have been dysregulated in DICER and Drosha knockout sperm groups [87] indicating active transcription of miRNAs during spermatogenesis. Moreover, the importance of miRNAs in sperm synthesis and male infertility has been described by analyzing miRNA expression in sperm cells derived from prepubertally hemicastrated Yorkshire boars [88], Landrace and Duroc sperm [89]. On the other hand, altered expression of certain miRNAs could be associated with poor sperm quality and male infertility.…”

Section: The Role Of Mirnas In Male Gametogenesismentioning

confidence: 99%

The Role of MicroRNAs in Mammalian Fertility: From Gametogenesis to Embryo Implantation

Salilew‐Wondim

Gebremedhn

Hoelker

et al. 2020

IJMS

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The genetic codes inscribed during two key developmental processes, namely gametogenesis and embryogenesis, are believed to determine subsequent development and survival of adult life. Once the embryo is formed, its further development mainly depends on its intrinsic characteristics, maternal environment (the endometrial receptivity), and the embryo–maternal interactions established during each phase of development. These developmental processes are under strict genetic regulation that could be manifested temporally and spatially depending on the physiological and developmental status of the cell. MicroRNAs (miRNAs), one of the small non-coding classes of RNAs, approximately 19–22 nucleotides in length, are one of the candidates for post-transcriptional developmental regulators. These tiny non-coding RNAs are expressed in ovarian tissue, granulosa cells, testis, oocytes, follicular fluid, and embryos and are implicated in diverse biological processes such as cell-to-cell communication. Moreover, accumulated evidences have also highlighted that miRNAs can be released into the extracellular environment through different mechanisms facilitating intercellular communication. Therefore, understanding miRNAs mediated regulatory mechanisms during gametogenesis and embryogenesis provides further insights about the molecular mechanisms underlying oocyte/sperm formation, early embryo development, and implantation. Thus, this review highlights the role of miRNAs in mammalian gametogenesis and embryogenesis and summarizes recent findings about miRNA-mediated post-transcriptional regulatory mechanisms occurring during early mammalian development.

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Section: The Role Of Mirnas In Male Gametogenesismentioning

confidence: 99%

The Role of MicroRNAs in Mammalian Fertility: From Gametogenesis to Embryo Implantation

Salilew‐Wondim

Gebremedhn

Hoelker

et al. 2020

IJMS

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show abstract

“…Sperm apoptosis has an adverse effect on sperm vitality both in in vivo and in vitro and is considered as one of the critical factors affecting the fecundity in humans and animals [38][39][40]. It was reported that let-7g-5p can regulate the apoptosis in boar sperm by targeting PMAIP1 gene, resulting in low motility of sperm [41]. miR-98, miR-181, miR-19, miR-504, and miR-676 are also involved in sperm apoptosis by regulating their target genes such as FAS, Bcl-2, PTEN, and p53, respectively, and thereby affecting the sperm motility and survival [42].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, transcriptomic analysis has suggested that miR-26a is also implicated in bull sperm motility [48]. However, miR-26a regulates boar sperm apoptosis by targeting PTEN gene and has a link with decreased sperm motility [41]. Intriguingly, it has been reported that the expression level of miR-26a in highly motile frozen-thawed sperm was significantly higher as compared to the low-motile frozen-thawed sperm [49].…”

Section: Introductionmentioning

confidence: 99%

miR-26a is Involved in Glycometabolism and Affects Boar Sperm Viability by Targeting PDHX

Wang

Liang

Chang

et al. 2020

Cells

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miR-26a is associated with sperm metabolism and can affect sperm motility and apoptosis. However, how miR-26a affects sperm motility remains largely unknown. Our previous study indicated that the PDHX gene is predicted to be a potential target of miR-26a, which is responsible for pyruvate oxidative decarboxylation which is considered as a key step for connecting glycolysis with oxidative phosphorylation. In this study, we first reported a potential relationship between miR-26a and PDHX and their expressions in fresh, frozen-thawed, and epididymal boar sperm. Then, sperm viability and survival were determined after transfection of miR-26a. mRNA and protein expression level of PDHX in the liquid-preserved boar sperm after transfection were also determined by RT-qPCR and Western Blot (WB). Our results showed that expression level of PDHX was significantly increased during sperm transit from epididymal caput to corpus and cauda. Similarly, expression of PDHX was significantly higher (P < 0.05) in fresh sperm as compared to epididymal cauda and frozen-thawed sperm. However, the expression of miR-26a in epididymal corpus sperm was significantly higher (P < 0.05) than that of caput and cauda sperm. Furthermore, after transfection of boar sperm with miR-26a mimic and inhibitor under liquid storage, the lowest and highest sperm viability was observed in miR-26a mimic and inhibitor treatment (P < 0.05), respectively. The protein levels of PDHX, after 24 and 48 h of transfection of miR-26a mimics and inhibitor, were notably decreased and increased (P < 0.05), respectively, as compared to negative control (NC) group. In conclusion, the novel and enticing findings of our study provide a reasonable evidence that miR-26a via PDHX, a link between glycolysis and oxidative phosphorylation, could regulate the glycometabolic pathway which eventually affect boar sperm viability and survival.

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“…Recently research on spermatozoal miRNAs has made considerable progress. Ma J found that testosterone‐dependent miR‐26a‐5p and let‐7 g‐5p act as signaling mediators to regulate sperm apoptosis via targeting PTEN and PMAIP1(Ma et al ., ). Furthermore, miRNAs control mRNA fate by compartmentalization based on 3′ UTR length in male germ cells (Zhang et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Expressions of miR‐525‐3p and its target gene SEMG1 in the spermatozoa of patients with asthenozoospermia

et al. 2018

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Background Semenogelin 1 (SEMG1) is an important secretory protein in spermatozoa involved in the formation of a gel matrix encasing ejaculated spermatozoa. Previous studies show that the SEMG1 gene is highly expressed in spermatozoa from patients with asthenozoospermia (AZS); however, the underlying molecular mechanisms are not yet clear. Objectives To study the molecular mechanism of high expression of SEMG1 gene and its potential roles in AZS. Materials and Methods Western blot and real‐time PCR were used to detect the expression levels of SEMG1 protein and mRNA in the ejaculated spermatozoa from normozoospermic males and AZS patients. Bioinformatics analysis was used to predict miRNAs targeting for SEMG1 3′‐untranslated region detection of the expression levels of all the candidate miRNAs in ejaculatory spermatozoa in AZS patients or normozoospermic volunteers. Luciferase reporter assays were performed to confirm it can directly bind to SEMG1. Correlation of miR‐525‐3p and SEMG1 mRNA expression with clinical sperm parameters were also analyzed. Finally, we conducted a follow‐up study of reproductive history about all the subjects. Results SEMG1 mRNA and protein level were significantly higher in AZS patients compared to that in normozoospermic volunteers (p < 0.001). Subsequently, microRNA‐525‐3p (miR‐525‐3p) which was predicted as a candidate regulator of SEMG1 was found lower expressed in ejaculatory spermatozoa in AZS patients (p = 0.0074). Luciferase experiment revealed that microRNA‐525‐3p could directly target SEMG1 3′‐untranslated region and suppress its expression. Importantly, our retrospective follow‐up study showed that both low miR‐525‐3p expression and high SEMG1 expression level was significantly associated with low progressive sperm motility, abnormal sperm morphology, and infertility. Discussion and Conclusion The elevated expression of SEMG1 and reduced expression of miR‐525‐3p are associated with AZS and male infertility. Our study provides a potential therapeutic target for the treatment of male infertility or for male contraception.

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Testosterone-Dependent miR-26a-5p and let-7g-5p Act as Signaling Mediators to Regulate Sperm Apoptosis via Targeting PTEN and PMAIP1

Cited by 43 publications

References 71 publications

The Role of MicroRNAs in Mammalian Fertility: From Gametogenesis to Embryo Implantation

The Role of MicroRNAs in Mammalian Fertility: From Gametogenesis to Embryo Implantation

miR-26a is Involved in Glycometabolism and Affects Boar Sperm Viability by Targeting PDHX

Expressions of miR‐525‐3p and its target gene SEMG1 in the spermatozoa of patients with asthenozoospermia

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