Glucocorticoids improve sperm performance in physiological and pathological conditions: their role in sperm fight/flight response.

IF 1.4 Q3 ANATOMY & MORPHOLOGY Anatomy & Cell Biology Pub Date : 2024-03-31 Epub Date: 2023-12-15 DOI:10.5115/acb.23.164
Vittoria Rago, Adele Vivacqua, Saveria Aquila
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Abstract

Glucocorticoids play a physiologic role in the adult male reproductive functions, modulating gonadal steroid synthesis and spermatogenesis, through the glucocorticoid receptor (GR). The expression of GR has been described in several key testicular cell types, including somatic cells and early germ cell populations. Nothing is known on GR in human spermatozoa. Herein, we explored the GR expression and its possible role in normal and testicular varicocele semen samples from volunteer donors. After semen parameter evaluation by macro- and microscopic analysis, samples were centrifuged; then spermatozoa and culture media were recovered for further investigations. By western blotting and immunofluorescence analyses we evidenced for the first time in spermatozoa the presence of GR-D3 isoform which was reduced in sperm from varicocele patients. By treating sperm with the synthetic glucocorticoid dexamethasone (DEXA), we found that survival, motility, capacitation, and acrosome reaction were increased in both healthy and varicocele samples. GR involvement in mediating DEXA effects, was confirmed by using the GR inhibitor mifepristone (M2F). Worthy, we also discovered that sperm secretes different cortisol amounts depending on its physio-pathological status, suggesting a defence mechanism to escape the immune system attach in the female genital tract thus maintaining the immune-privilege as in the testis. Collectively, our data suggests a role for glucocorticoids in determining semen quality and function, as well as in participating on sperm immune defensive mechanisms. The novelty of this study may be beneficial and needs to take into account in artificial insemination/drug discovery aimed to enhancing sperm quality.

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糖皮质激素改善精子在生理和病理条件下的表现:它们在精子战斗/飞行反应中的作用。
糖皮质激素通过糖皮质激素受体(GR)调节性腺类固醇合成和精子发生,在成年男性生殖功能中发挥生理作用。GR在几种关键的睾丸细胞类型中都有表达,包括体细胞和早期生殖细胞群。目前尚不清楚人类精子中的 GR 表达情况。在此,我们对志愿者捐献的正常精液样本和精索静脉曲张精液样本中的 GR 表达及其可能的作用进行了研究。通过宏观和显微镜分析评估精液参数后,对样本进行离心,然后回收精子和培养基进行进一步研究。通过 Western 印迹和免疫荧光分析,我们首次发现精子中存在 GR-D3 同工酶,而精索静脉曲张患者的精子中 GR-D3 同工酶减少。通过用合成糖皮质激素地塞米松(DEXA)处理精子,我们发现健康精子和精索静脉曲张样本中精子的存活率、运动能力、获能能力和顶体反应均有所提高。使用 GR 抑制剂米非司酮(M2F)证实了 GR 参与介导 DEXA 的作用。值得注意的是,我们还发现精子会根据其生理病理状态分泌不同数量的皮质醇,这表明女性生殖道中存在一种逃避免疫系统附着的防御机制,从而保持睾丸的免疫特权。总之,我们的数据表明,糖皮质激素在决定精液质量和功能以及参与精子免疫防御机制方面发挥作用。这项研究的新颖性可能是有益的,在旨在提高精子质量的人工授精/药物研发中需要加以考虑。
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来源期刊
Anatomy & Cell Biology
Anatomy & Cell Biology ANATOMY & MORPHOLOGY-
CiteScore
1.80
自引率
9.10%
发文量
75
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