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孕期糖尿病母亲运动和甘精胰岛素治疗可改善子代睾丸功能:对apelin-13 及其受体的影响。

Exercise and insulin glargine administration in mothers with diabetes during pregnancy ameliorate function of testis in offspring: Consequences on apelin-13 and its receptor.

机构信息

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.

出版信息

Life Sci. 2024 Apr 1;342:122517. doi: 10.1016/j.lfs.2024.122517. Epub 2024 Feb 22.

Abstract

AIMS

Despite the evidence exhibited that diabetes during gestation (DDG) is linked with reproductive dysfunction in offspring, the underlying cellular mechanisms involved are not precisely defined. This study was designed to assess the impact of voluntary exercise and insulin glargine on DDG-induced metabolic and reproductive disorders in male offspring.

MAIN METHODS

Fifty female Wistar rats (three weeks old) received a control diet (n = 10) or high-fat-high-sucrose diet (to induce DDG; n = 40) for six weeks before breeding. From the 7th day of pregnancy onwards, blood glucose over 140 mg/dL was characterized as DDG. Then, the DDG animals were randomly divided into four subgroups with/without voluntary exercise and/or insulin glargine. To evaluate insulin resistance, a glucose tolerance test was performed on the 15th day of pregnancy. After three weeks, male offspring were weaned, and fed a control diet until 12 weeks old. At the end of the experiment, the lipid profile, sex hormones, and apelin-13 in the serum, mRNA expression of apelin receptors (APJ) in the testis and sperm analysis were assessed.

KEY FINDINGS

Our results indicated that voluntary exercise and/or insulin glargine administration in mothers with DDG ameliorated lipid profile, and sex hormones alterations, reduced the serum level of apelin-13, as well as increased APJ expression in testis, and quality of sperm in offspring.

SIGNIFICANCE

Combined administration of voluntary exercise and insulin glargine during pregnancy by regulating of apelinergic system and inhibiting the metabolic and reproductive complications induced by DDG, can be considered as a suitable therapeutic strategy for improving sub-or in-fertility in the male offspring.

摘要

目的

尽管有证据表明妊娠期糖尿病(DDG)与后代生殖功能障碍有关,但涉及的潜在细胞机制尚不清楚。本研究旨在评估自愿运动和甘精胰岛素对 DDG 诱导的雄性后代代谢和生殖紊乱的影响。

方法

50 只雌性 Wistar 大鼠(3 周龄)接受对照饮食(n=10)或高脂高蔗糖饮食(诱导 DDG;n=40)6 周后繁殖。从妊娠第 7 天开始,血糖超过 140mg/dL 被定义为 DDG。然后,DDG 动物被随机分为 4 组,分别接受/不接受自愿运动和/或甘精胰岛素治疗。为评估胰岛素抵抗,在妊娠第 15 天进行葡萄糖耐量试验。3 周后,雄性后代断奶,喂食对照饮食直至 12 周龄。实验结束时,评估血清中的血脂谱、性激素和 Apelin-13,睾丸中 Apelin 受体(APJ)的 mRNA 表达和精子分析。

主要发现

我们的结果表明,DDG 母亲的自愿运动和/或甘精胰岛素治疗改善了血脂谱和性激素改变,降低了血清 Apelin-13 水平,增加了睾丸中 APJ 的表达,改善了后代精子的质量。

意义

在怀孕期间联合使用自愿运动和甘精胰岛素,通过调节 Apelin 系统和抑制由 DDG 引起的代谢和生殖并发症,可以被认为是改善雄性后代的亚生育或不孕的一种合适的治疗策略。

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