Androgen Indirectly Regulates Gap Junction Component Connexin 43 Through Wilms Tumor-1 in Sertoli Cells

Qin, Xia; Zhang, Danchen; Wang, Jingjing; Zhang, Xiaoyu; Song, Weixiang; Chen, Rong; Li, Hua; Xie, Wenhai; Zou, Kang

doi:10.1089/scd.2019.0166

Cited by 11 publications

(7 citation statements)

References 20 publications

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“…Once the germ cells were completely removed, only SCs were observed in the seminiferous tubules of the busulfan‐treated recipients identified by SSCs marker PLZF and SCs marker WT1 staining (Figure 1f). Our previous study has revealed that Connexin 43, a protein with a short half‐life of hours expressed by SCs, could be detected weeks after germ cells were deleted, demonstrating the vitality of SCs in the absence of germ cells (Xia et al, 2020). Here, we observed the expression of exosome‐specific proteins TSG101 and ALIX on the surface of SCs (Figure 1f), suggesting that SCs continuously secrete exosomes even in the absence of germ cells for a couple of days.…”

Section: Resultsmentioning

confidence: 99%

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Regulation of spermatogonial stem cell differentiation by Sertoli cells‐derived exosomes through paracrine and autocrine signaling

Tian,

Wang,

et al. 2024

Journal Cellular Physiology

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In the orchestrated environment of the testicular niche, the equilibrium between self‐renewal and differentiation of spermatogonial stem cells (SSCs) is meticulously maintained, ensuring a stable stem cell reserve and robust spermatogenesis. Within this milieu, extracellular vesicles, specifically exosomes, have emerged as critical conveyors of intercellular communication. Despite their recognized significance, the implications of testicular exosomes in modulating SSC fate remain incompletely characterized. Given the fundamental support and regulatory influence of Sertoli cells (SCs) on SSCs, we were compelled to explore the role of SC‐derived exosomes (SC‐EXOs) in the SSC‐testicular niche. Our investigation hinged on the hypothesis that SC‐EXOs, secreted by SCs from the testes of 5‐day‐old mice—a developmental juncture marking the onset of SSC differentiation—participate in the regulation of this process. We discovered that exposure to SC‐EXOs resulted in an upsurge of PLZF, MVH, and STRA8 expression in SSC cultures, concomitant with a diminution of ID4 and GFRA1 levels. Intriguingly, obstructing exosomal communication in a SC‐SSC coculture system with the exosome inhibitor GW4869 attenuated SSC differentiation, suggesting that SC‐EXOs may modulate this process via paracrine signaling. Further scrutiny revealed the presence of miR‐493‐5p within SC‐EXOs, which suppresses Gdnf mRNA in SCs to indirectly restrain SSC differentiation through the modulation of GDNF expression—an indication of autocrine regulation. Collectively, our findings illuminate the complex regulatory schema by which SC‐EXOs affect SSC differentiation, offering novel perspectives and laying the groundwork for future preclinical and clinical investigations.

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Section: Resultsmentioning

confidence: 99%

“…To confirm the secretion of exosomes by SCs, a germ cell‐depleted testicular model was established (Xia et al, 2020). Six‐week‐old male mice were intraperitoneally administered busulfan (44 mg/kg) to eliminate germ cells (Figure 1c), resulting in a significant reduction in testes size and weight compared to controls (Figure 1d).…”

Section: Resultsmentioning

confidence: 99%

Regulation of spermatogonial stem cell differentiation by Sertoli cells‐derived exosomes through paracrine and autocrine signaling

Tian,

Wang,

et al. 2024

Journal Cellular Physiology

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“…Moreover, inhibiting the action of testicular hormones or mutations in the androgen receptor can lead to the increased permeability of the BTB [ 38 , 39 , 40 ]. Testosterone regulates the expression of TJ proteins (including the membrane-associated guanylate kinase (MAGUK) family, Claudins, and Occludins) [ 41 , 42 , 43 , 44 ], tissue-type plasminogen activator (tPA) (which is involved in BTB degradation) [ 45 , 46 ], basal ectoplasmic specialization (ES) proteins [ 47 ], and gap junction proteins (including Connexin 43) directly or indirectly to maintain the integrity of the BTB and support its renewal [ 48 ].…”

Section: Hormone Regulation In Testicular Development and Functionmentioning

confidence: 99%

Hormone Regulation in Testicular Development and Function

Li,

Lin,

Wang

et al. 2024

IJMS

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The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and paracrine pathways. Male fertility hinges on the availability of testosterone, a cornerstone of spermatogenesis, while follicle-stimulating hormone (FSH) signaling is indispensable for the proliferation, differentiation, and proper functioning of Sertoli and germ cells. This review covers the research on how androgens, FSH, and other hormones support processes crucial for male fertility in the testis and reproductive tract. These hormones are regulated by the hypothalamic–pituitary–gonad (HPG) axis, which is either quiescent or activated at different stages of the life course, and the regulation of the axis is crucial for the development and normal function of the male reproductive system. Hormonal imbalances, whether due to genetic predispositions or environmental influences, leading to hypogonadism or hypergonadism, can precipitate reproductive disorders. Investigating the regulatory network and molecular mechanisms involved in testicular development and spermatogenesis is instrumental in developing new therapeutic methods, drugs, and male hormonal contraceptives.

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“…Androgen inhibits GATA-2 expression through the classical pathway. Wt1 can bind to the promoter of Cx43 and inhibit its expression, indicating that androgen can promote Cx43 expression by downregulating GATA-2 and Wt1 ( 139 ). What’s more, ouabain binding to its receptor ATP1A1can upregulate Cx43 expression via non-classical signaling pathway in vivo ( 140 ).…”

Section: Androgen Receptor Signaling Pathway In Sertoli Cells Can Reg...mentioning

confidence: 99%

What Does Androgen Receptor Signaling Pathway in Sertoli Cells During Normal Spermatogenesis Tell Us?

Wang

Yang

2022

Front. Endocrinol.

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Androgen receptor signaling pathway is necessary to complete spermatogenesis in testes. Difference between androgen binding location in Sertoli cell classifies androgen receptor signaling pathway into classical signaling pathway and non-classical signaling pathway. As the only somatic cell type in seminiferous tubule, Sertoli cells are under androgen receptor signaling pathway regulation via androgen receptor located in cytoplasm and plasma membrane. Androgen receptor signaling pathway is able to regulate biological processes in Sertoli cells as well as germ cells surrounded between Sertoli cells. Our review will summarize the major discoveries of androgen receptor signaling pathway in Sertoli cells and the paracrine action on germ cells. Androgen receptor signaling pathway regulates Sertoli cell proliferation and maturation, as well as maintain the integrity of blood-testis barrier formed between Sertoli cells. Also, Spermatogonia stem cells achieve a balance between self-renewal and differentiation under androgen receptor signaling regulation. Meiotic and post-meiotic processes including Sertoli cell - Spermatid attachment and Spermatid development are guaranteed by androgen receptor signaling until the final sperm release. This review also includes one disease related to androgen receptor signaling dysfunction named as androgen insensitivity syndrome. As a step further ahead, this review may be conducive to develop therapies which can cure impaired androgen receptor signaling in Sertoli cells.

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Androgen Indirectly Regulates Gap Junction Component Connexin 43 Through Wilms Tumor-1 in Sertoli Cells

Cited by 11 publications

References 20 publications

Regulation of spermatogonial stem cell differentiation by Sertoli cells‐derived exosomes through paracrine and autocrine signaling

Regulation of spermatogonial stem cell differentiation by Sertoli cells‐derived exosomes through paracrine and autocrine signaling

Hormone Regulation in Testicular Development and Function

What Does Androgen Receptor Signaling Pathway in Sertoli Cells During Normal Spermatogenesis Tell Us?

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