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系统α-1 肾上腺素能受体抑制可减少成年和衰老自发性高血压大鼠的精子损伤。

Systemic alpha-1 adrenergic receptor inhibition reduces sperm damage in adult and aging spontaneously hypertensive rats.

机构信息

Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, 3o Floor, Room 319, Butanta, SP, 05508000, Brazil.

Department of Surgery, Division of Urology, Human Reproduction Section, São Paulo Federal University, São Paulo, Brazil.

出版信息

Sci Rep. 2024 Nov 20;14(1):28808. doi: 10.1038/s41598-024-77661-7.

DOI:10.1038/s41598-024-77661-7
PMID:39567544
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11579389/
Abstract

Decreased sperm quality has been reported in men with different clinical conditions, including aging and hypertension. In the male reproductive tract, it has been suggested that the α1-adrenergic receptor influences fertility and spermatogenesis, and important functions are also attributed to the renin-angiotensin axis, such as regulation of steroidogenesis, spermatogenesis, and sperm function. Previously, our group demonstrated impaired testicular vasomotion via α1-adrenergic receptor activation and increased hypoxia-related proteins in the testes of spontaneously hypertensive rats (SHRs) compared to Wistar normotensive rats. In this study, we aimed to investigate the effect of hypertension and inhibition of systemic α1-adrenergic receptor or angiotensin II AT1 receptor on sperm quality, sperm functional characteristics, and testicular microcirculation in rats from three different ages: young (8-10-week-old), adult (20-24-week-old) and older adult (60-66-week-old). We observed higher blood pressure in SHRs of all ages compared to age-matched Wistar rats. Lower blood pressure was observed either in prazosin or losartan-treated adult or aged SHRs. Additionally, lower sperm concentration, impaired motility and higher acrosome damage were demonstrated in SHRs. Prazosin treatment alleviated the effects of hypertension on sperm concentration and motility but not acrosome damage. Higher vasomotion was noticed in testicular blood vessels of adult and aged SHRs compared to Wistar rats. Thus, impaired sperm quality was observed in SHRs of different ages and was improved by sub-chronically blocking the α1-adrenergic receptor.

摘要

已有研究报道,不同临床条件下的男性(包括衰老和高血压患者)的精子质量会降低。在男性生殖系统中,α1-肾上腺素能受体被认为会影响生育能力和精子发生,肾素-血管紧张素轴也具有重要功能,例如调节类固醇生成、精子发生和精子功能。此前,我们的研究小组发现,与 Wistar 正常血压大鼠相比,自发性高血压大鼠(SHR)睾丸内的血管运动通过α1-肾上腺素能受体激活而受损,并且与缺氧相关的蛋白增加。在这项研究中,我们旨在研究高血压以及全身α1-肾上腺素能受体或血管紧张素 II AT1 受体抑制对来自三个不同年龄段(年轻:8-10 周龄;成年:20-24 周龄;老年:60-66 周龄)大鼠精子质量、精子功能特征和睾丸微循环的影响。我们观察到,所有年龄段的 SHRs 的血压均高于同龄的 Wistar 大鼠。成年或老年 SHRs 接受普萘洛尔或氯沙坦治疗后,血压降低。此外,SHRs 的精子浓度降低、运动能力受损,顶体损伤增加。普萘洛尔治疗减轻了高血压对精子浓度和运动能力的影响,但对顶体损伤没有影响。与 Wistar 大鼠相比,成年和老年 SHRs 的睾丸血管中的血管运动增强。因此,不同年龄的 SHRs 的精子质量受损,通过亚慢性阻断α1-肾上腺素能受体得到改善。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5885/11579389/e74bdbe3ab6a/41598_2024_77661_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5885/11579389/739860a3bc34/41598_2024_77661_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5885/11579389/ad60b4972349/41598_2024_77661_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5885/11579389/7e2d82907f56/41598_2024_77661_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5885/11579389/0b716c6fcdbc/41598_2024_77661_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5885/11579389/e74bdbe3ab6a/41598_2024_77661_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5885/11579389/739860a3bc34/41598_2024_77661_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5885/11579389/f9d584ada2f1/41598_2024_77661_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5885/11579389/ad60b4972349/41598_2024_77661_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5885/11579389/7e2d82907f56/41598_2024_77661_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5885/11579389/0b716c6fcdbc/41598_2024_77661_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5885/11579389/e74bdbe3ab6a/41598_2024_77661_Fig6_HTML.jpg

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本文引用的文献

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Mechanisms That Protect Mammalian Sperm from the Spontaneous Acrosome Reaction.保护哺乳动物精子免受自发顶体反应的机制。
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Testicular ACE regulates sperm metabolism and fertilization through the transcription factor PPARγ.睾丸中的血管紧张素转换酶(ACE)通过转录因子过氧化物酶体增殖物激活受体γ(PPARγ)调节精子代谢和受精。
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