Maternal dexamethasone exposure does not affect glucose tolerance but alters renal haemodynamics in F1 rats in a sex-dependent manner

IF 2.7 Q3 ENDOCRINOLOGY & METABOLISM

Endocrinology, Diabetes and Metabolism Pub Date : 2023-09-18 DOI:10.1002/edm2.450

Slava A. Malatiali, Narayana Kilarkaje, Maie Al-Bader

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Abstract

Introduction

Prenatal programming with dexamethasone increases the risk of the development of hyperglycaemia and insulin resistance, leading to diabetes in adulthood. Dexamethasone also causes a decline in renal glomerular filtration in the adult offspring. Sodium-glucose cotransporter-2 (SGLT2) plays a significant role in regulating blood glucose and renal haemodynamics in diabetic patients. However, the role of SGLT2 in dexamethasone-induced programming and the putative sex-dependent effects on the changes named earlier is unknown. Therefore, this study aimed to investigate the impact of maternal dexamethasone treatment on glucose tolerance, insulin sensitivity, renal perfusion and renal function in adult male and female offspring and the possible contribution of SGLT2 to these changes.

Methods and Results

Pregnant Sprague Dawley rats (F₀) were treated with either vehicle or dexamethasone (0.2 mg/kg ip) from gestation Day 15 to 20. F₁ males and F₁ females were randomly selected from each mother at 4 months of age. There was no change in serum Na⁺, Na⁺ excretion rate, glucose tolerance or insulin sensitivity in F₁ male or female rats. However, dexamethasone caused significant glomerular hypertrophy and decreases in C_Sinistrin and C_PAH indicating decreased glomerular filtration rate and renal plasma flow, respectively, in dexamethasone-treated F1 male but not female rats. Dexamethasone did not affect SGLT2 mRNA or protein expression in F₁ males or females.

Conclusion

We conclude that dexamethasone-mediated prenatal programming of glomerular volume, renal function and haemodynamics is sex-dependent, occurring only in adult male offspring.

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母体地塞米松暴露不影响糖耐量，但以性别依赖的方式改变F1大鼠的肾血流动力学

产前使用地塞米松会增加高血糖和胰岛素抵抗的风险，从而导致成年后患糖尿病。地塞米松也会导致成年后代肾小球滤过功能下降。钠-葡萄糖共转运蛋白-2 (Sodium-glucose cotransporter-2, SGLT2)在糖尿病患者血糖和肾脏血流动力学调节中发挥重要作用。然而，SGLT2在地塞米松诱导的编程中的作用，以及对上述变化的假定的性别依赖作用尚不清楚。因此，本研究旨在探讨母体地塞米松治疗对成年雄性和雌性后代糖耐量、胰岛素敏感性、肾灌注和肾功能的影响，以及SGLT2在这些变化中的可能作用。方法与结果妊娠大鼠(F0)从妊娠第15 ~ 20天开始，分别给药或地塞米松(0.2 mg/kg / ip)。4月龄时，从每只母鼠中随机选取雄性和雌性各F1只。F1雄性和雌性大鼠血清Na+、Na+排泄率、葡萄糖耐量和胰岛素敏感性均无变化。然而，在地塞米松治疗的F1雄性大鼠中，地塞米松引起肾小球明显肥大，csiinistrin和CPAH降低，分别表明肾小球滤过率和肾血浆流量降低，而雌性大鼠没有。地塞米松不影响F1雄性或雌性中SGLT2 mRNA或蛋白的表达。结论地塞米松介导的肾小球体积、肾功能和血流动力学的产前规划是性别依赖的，仅发生在成年雄性后代中。

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