Milan K L, Anuradha M, Ramkumar Kunka Mohanram
Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603 203, India.
Department of Obstetrics & Gynaecology, SRM Medical College Hospital and Research Centre, Kattankulathur, Tamil Nadu 603203, India.
J Reprod Immunol. 2025 Feb;167:104422. doi: 10.1016/j.jri.2024.104422. Epub 2024 Dec 25.
Gestational diabetes is marked impaired glucose tolerance, poses various adverse outcomes including increased BMI and obesity. These outcomes results from excess lipid accumulation which is marked by elevated triglycerides. In GDM, placenta exhibits altered lipid metabolism, including reduced fatty acid oxidation and increased triglyceride accumulation. These elevated triglycerides can also contribute to oxidative stress in GDM. SIRT7 plays an important role in regulating lipid metabolism and triglycerides levels. This study aimed to investigate the potential of miRNA to regulate the placental SIRT7 in GDM. PCR analysis reveals that SIRT7 expression along with oxidative stress markers elevated in GDM placenta. These elevated SIRT7 levels were positively correlated with BMI and triglycerides levels in GDM subjects. miR-125b-5p was identified to regulate SIRT7 mRNA using in-silico approaches. Expression levels of miR-125b-5p were found to be downregulated in GDM placenta and found to be negatively correlated with SIRT7 mRNA expression. To confirm the hypothesis BeWo cells were transfected with anti-miR-125b and miR-125b-mimic. Anti-miR overexpressed the SIRT7 expression where mimic dysregulated it. Additionally, overexpressing miR-125b-5p controlled the elevated SIRT7 caused by the exposure of high glucose in BeWo cells. Collectively this study indicated that miR-125b-5p may regulate lipid metabolism via SIRT7 contributing to GDM. These findings highlights the warrant of further research to develop the therapeutic approaches that target miR-125b-5p to reduce lipid accumulation and obesity in GDM.
妊娠期糖尿病的特征是葡萄糖耐量显著受损，会导致包括体重指数增加和肥胖在内的各种不良后果。这些后果是由脂质过度积累引起的，其特征是甘油三酯升高。在妊娠期糖尿病中，胎盘表现出脂质代谢改变，包括脂肪酸氧化减少和甘油三酯积累增加。这些升高的甘油三酯也会导致妊娠期糖尿病中的氧化应激。沉默调节蛋白7（SIRT7）在调节脂质代谢和甘油三酯水平方面发挥着重要作用。本研究旨在探讨微小RNA（miRNA）调节妊娠期糖尿病胎盘SIRT7的潜力。聚合酶链反应（PCR）分析显示，妊娠期糖尿病胎盘的SIRT7表达以及氧化应激标志物升高。在妊娠期糖尿病患者中，这些升高的SIRT7水平与体重指数和甘油三酯水平呈正相关。使用计算机模拟方法确定miR-125b-5p可调节SIRT7信使核糖核酸（mRNA）。发现miR-125b-5p的表达水平在妊娠期糖尿病胎盘中下调，并且发现与SIRT7 mRNA表达呈负相关。为了证实这一假设，用抗miR-125b和miR-125b模拟物转染了BeWo细胞。抗miR使SIRT7表达上调，而模拟物使其失调。此外，过表达miR-125b-5p可控制BeWo细胞中高糖暴露引起的SIRT7升高。总体而言，本研究表明miR-125b-5p可能通过SIRT7调节脂质代谢，从而导致妊娠期糖尿病。这些发现凸显了进一步研究以开发靶向miR-125b-5p的治疗方法以减少妊娠期糖尿病中脂质积累和肥胖的必要性。
