IP3R Channels in Male Reproduction

Zhang, Xiaoning; Huang, Rongzu; Zhou, Yang; Zhou, Wenwen; Zeng, Xuhui

doi:10.3390/ijms21239179

Cited by 13 publications

(9 citation statements)

References 105 publications

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“…It has been documented that sperm ion channels including Ca 2+ play significant regulatory roles in the process of spermatogenesis, controlling sperm maturity and motility, the acrosome response, and fertilization 17 , 52 . These Ca 2+ ions are accumulated in spermatogenic cells at different developmental stages and manage the spermatogenesis and spermiogenesis processes 53 . Therefore, irregular Ca 2+ signaling pathways can impair testosterone levels, which leads to unnatural spermatogenesis and even complete male infertility Furthermore, several reports have shown that the calcium pathway could be interconnected with the apoptosis pathway 26 , 54 – 56 .…”

Section: Discussionmentioning

confidence: 99%

Identification of ITPR1 gene as a novel target for hsa-miR-34b-5p in non-obstructive azoospermia: a Ca2+/apoptosis pathway cross-talk

Maleki,

Modarres,

Salehi

et al. 2023

Sci Rep

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MiR-34b-5p has been reported as a non-invasive diagnostic biomarker for infertility. However, no gene targets regulating the mechanism of cation of this miRNA are known. In this study, using gene set enrichment analysis the Inositol 1,4,5-Trisphosphate Receptor Type 1 (ITPR1) gene was identified as the sole target for hsa-miR-34b-5p, and found significantly overexpressed in non-obstructive azoospermia (NOA) patients. This finding was confirmed by qRT-PCR on fresh testicular tissues from NOA patients. Then, pathway enrichment analysis as well as the diagnostic value analysis of hsa-miR-34b-5p/ITPR1 indicated ITPR1 as a hub gene in the calcium (Ca2+)-apoptosis pathway, and a valuable predictive biomarker for NOA. Moreover, gene expression and histological assays showed the association of the effects of ITPR1’s increased expression on spermatogenesis failure through induction of apoptosis in NOA patients. These data suggested that the hsa-miR-34b-5p/ITPR1 axis could serve as a potential regulatory predictive biomarker for human spermatogenesis through the Ca2+-apoptosis pathway cross-talk.

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Section: Discussionmentioning

confidence: 99%

Identification of ITPR1 gene as a novel target for hsa-miR-34b-5p in non-obstructive azoospermia: a Ca2+/apoptosis pathway cross-talk

Maleki,

Modarres,

Salehi

et al. 2023

Sci Rep

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show abstract

“…The GO analysis based on AS data indicated that Sugp2 may participate in metal ion and energy metabolism. Combined with the results of KEGG, Sugp2 may be involved in calcium transport and signal transduction, which play an essential role in male germ cell development and function ( 34 , 35 ).…”

Section: Discussionmentioning

confidence: 92%

Chromatin-Associated Protein Sugp2 Involved in mRNA Alternative Splicing During Mouse Spermatogenesis

Zhan

et al. 2021

Front. Vet. Sci.

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Mammalian spermatogenesis is a highly ordered process that is determined by chromatin-associated moderators which still remain poorly understood. Through a multi-control group proteomics strategy, we confirmed that Sugp2 was a chromatin-associated candidate protein, and its signal arose along spermatogenesis. The expression results showed that Sugp2, which is mainly expressed in the testis, had two transcripts, encoding one protein. During spermatogenesis, Sugp2 was enriched in the nucleus of male germ cells. With the depletion of Sugp2 by CRISPER-Cas9 technology, we found that Sugp2 controlled a network of genes on metal ion and ATP binding, suggesting that alternative splicing regulation by Sugp2 is involved in cellular ion and energy metabolism during spermatogenesis, while it had a little effect on meiotic progression and male fertility. Collectively, these data demonstrated that, as a chromatin-associated protein, Sugp2 mediated the alternative splicing regulatory network during spermatogenesis.

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“…Bitter tastants, including progesterone or chemokines, which can be secreted by the cumulus–oocyte complex, could potentially activate TAS2Rs in sperm. This activation could trigger the release of calcium from internal stores, (Correia et al, 2015; Zhang et al, 2020) resulting in an increase in [Ca 2+ ] i , which in turn could enhance sperm flagellar beating and hyperactivation. Given that cation channel of sperm (CatSper) is a dominant Ca 2+ channel for sperm activation (Hwang & Chung, 2023; Ren et al, 2001), it is plausible that the activation of TAS2Rs could functionally couple with CatSper.…”

Section: The Roles Of Tas2rs In the Male Reproductive Systemmentioning

confidence: 99%

Bitter taste receptors in the reproductive system: Function and therapeutic implications

Lu,

Moore Simas,

Delpapa

et al. 2024

Journal Cellular Physiology

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Type 2 taste receptors (TAS2Rs), traditionally known for their role in bitter taste perception, are present in diverse reproductive tissues of both sexes. This review explores our current understanding of TAS2R functions with a particular focus on reproductive health. In males, TAS2Rs are believed to play potential roles in processes such as sperm chemotaxis and male fertility. Genetic insights from mouse models and human polymorphism studies provide some evidence for their contribution to male infertility. In female reproduction, it is speculated that TAS2Rs influence the ovarian milieu, shaping the functions of granulosa and cumulus cells and their interactions with oocytes. In the uterus, TAS2Rs contribute to uterine relaxation and hold potential as therapeutic targets for preventing preterm birth. In the placenta, they are proposed to function as vigilant sentinels, responding to infection and potentially modulating mechanisms of fetal protection. In the cervix and vagina, their analogous functions to those in other extraoral tissues suggest a potential role in infection defense. In addition, TAS2Rs exhibit altered expression patterns that profoundly affect cancer cell proliferation and apoptosis in reproductive cancers. Notably, TAS2R agonists show promise in inducing apoptosis and overcoming chemoresistance in these malignancies. Despite these advances, challenges remain, including a lack of genetic and functional studies. The application of techniques such as single‐cell RNA sequencing and clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR‐associated endonuclease 9 gene editing could provide deeper insights into TAS2Rs in reproduction, paving the way for novel therapeutic strategies for reproductive disorders.

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IP3R Channels in Male Reproduction

Cited by 13 publications

References 105 publications

Identification of ITPR1 gene as a novel target for hsa-miR-34b-5p in non-obstructive azoospermia: a Ca2+/apoptosis pathway cross-talk

Identification of ITPR1 gene as a novel target for hsa-miR-34b-5p in non-obstructive azoospermia: a Ca2+/apoptosis pathway cross-talk

Chromatin-Associated Protein Sugp2 Involved in mRNA Alternative Splicing During Mouse Spermatogenesis

Bitter taste receptors in the reproductive system: Function and therapeutic implications

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