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SAUDI PHARMACEUTICAL JOURNAL · 2016 · IF 2.233

New discovery of cryptorchidism: Decreased retinoic acid in testicle

Jinpu Peng,Lianju Shen,Jinjun Chen,Xining Cao,Yue Zhou,Huali Weng,Chunlan Long,Deying Zhang,Shengfen Tu,Yan Zhang,Dawei He,Tao Lin,Guanghui Wei

This study focuses on investigation of cryptorchidism induced by flutamide (Flu) and its histopathological damage, and detects retinoic acid concentration in testicle tissue, in order to find a new method for clinical treatment to infertility caused by cryptorchidism. Twenty SD (Sprague Dawley) pregnant rats were randomly divided into Flu cryptorchidism group ( n   =   10) and normal control group ( n   =   10). HE stained for observing morphological difference. Transmission electron microscope (TEM) was used for observing the tight junction structure between Sertoli cells. Epididymal caudal sperms were counted and observed in morphology. The expression of stimulated by retinoic acid gene 8 (Stra8) was detected using immunohistochemistry, western blot, and Q-PCR. High performance liquid chromatography (HPLC) analysis was made on retinoic acid content. Sperm count and morphology observation confirmed cryptorchidism group was lower than normal group in sperm quantity and quality. The observation by TEM showed a loose structure of tight junctions between Sertoli cells. Immunohistochemistry, western blot, and Q-PCR showed that cryptorchidism group was significantly lower than normal group in the expression of Stra8. HPLC showed that retinoic acid content was significantly lower in cryptorchid testis than in normal testis. In the cryptorchidism model, retinoic acid content in testicular tissue has a significant reduction; testicles have significant pathological changes; damage exists in the structure of tight junctions between Sertoli cells; Stra8 expression has a significant reduction, perhaps mainly contributing to spermatogenesis disorder.

CAS / MDL: 8001-30-7
研究领域: 生殖生物学 · 内分泌学 · 组织病理学
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JOURNAL OF CELLULAR PHYSIOLOGY · 2024 · IF 4.5

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

Hairui Tian,Xingju Wang,Xiaoxiao Li,Weixiang Song,Jiaqi Mi,Kang Zou

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.

研究领域: 生殖生物学 · 干细胞生物学 · 分子生物学
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Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology · 2016 ·Vol. 299 ·期 4 ·450-460 · IF 1.507

Ameliorative Effect of Grape Seed Proanthocyanidin Extract on Cadmium-Induced Meiosis Inhibition During Oogenesis in Chicken Embryos

Fuyin Hou,Min Xiao,Jian Li,Devin W. Cook,Weidong Zeng,Caiqiao Zhang,Yuling Mi

Cadmium (Cd) is an environmental endocrine disruptor that has toxic effects on the female reproductive system. Here the ameliorative effect of grape seed proanthocyanidin extract (GSPE) on Cd-induced meiosis inhibition during oogenesis was explored. As compared with controls, chicken embryos exposed to Cd (3 µg/egg) displayed a changed oocyte morphology, decreased number of meiotic germ cells, and decreased expression of the meiotic marker protein γH2AX. Real time RT-PCR also revealed a significant down-regulation in the mRNA expressions of various meiosis-specific markers ( Stra8 , Spo11 , Scp3 , and Dmc1 ) together with those of Raldh2 , a retinoic acid (RA) synthetase, and of the receptors ( RARα and RARβ ). In addition, exposure to Cd increased the production of H 2 O 2 and malondialdehyde in the ovaries and caused a corresponding reduction in glutathione and superoxide dismutase. Simultaneous supplementation of GSPE (150 µg/egg) markedly alleviated the aforementioned Cd-induced embryotoxic effects by upregulating meiosis-related proteins and gene expressions and restoring the antioxidative level. Collectively, the findings provided novel insights into the underlying mechanism of Cd-induced meiosis inhibition and indicated that GSPE might potentially ameliorate related reproductive disorders. Anat Rec, 299:450–460, 2016. © 2016 Wiley Periodicals, Inc.

CAS / MDL: 7440-43-9
研究领域: 毒理学 · 生殖生物学 · 分子生物学
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