Ramamoorthy Rajalakshmi, Carden Arianna K, Hussain Hussain, Druyan Brian Z, Chen Ping Ping, Hajjar Rima, Fernandez Carmen, Elumalai Nila, Rashed Amirah B, Young Karen, Speciale Anna Rosa, West Emily M, Marbin Staci, Safro Bradley, Bishop Ian J, Jayakumar Arumugam R, Sanchez-Ramos Luis, Paidas Michael J
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
School of Nursing and Health Studies, University of Miami, Coral Cables, Miami, FL 33146, USA.
J Dev Biol. 2025 Aug 15;13(3):29. doi: 10.3390/jdb13030029.
Glucagon-like peptide 1 (GLP-1), a hormone derived from the proglucagon gene, regulates various physiological processes; however, its impact on pregnancy outcomes remains poorly understood. Assessing the effects of GLP-1 on neonates is vital as GLP-1 is increasingly administered during pregnancy. This study evaluates the effect of GLP-1 exposure on maternal complications and neonatal defects in mice. Pregnant female A/J mice received subcutaneous injections of recombinant GLP-1 (rGLP-1; 1000 nmol/kg) on embryonic day 1 (EP, early pregnancy) or day 15 (E15, late pregnancy). Maternal and neonatal body weights, morphology, and mortality were recorded, and mRNA sequencing was conducted to analyze gene expression in neonatal tissues. Maternal body weight decreased following rGLP-1 exposure, and pups born to both the early and late exposure groups experienced significant weight loss. Pups in the late exposure group exhibited uniform skin detachment and a dramatically higher mortality rate than those born to the early exposure group. Further, RT-PCR analysis confirms the significantly increased expression of selected genes in the skin and associated pathogenesis. RNA sequencing of pups' skin, brain, lung, and liver tissues from the late exposure group showed altered gene expression. Since maternal weight loss, increased neonatal mortality, and altered gene expression have been observed, GLP-1 receptor agonists (GLP-1RAs) should be avoided during pregnancy.
胰高血糖素样肽1（GLP-1）是一种源自胰高血糖素原基因的激素，可调节多种生理过程；然而，其对妊娠结局的影响仍知之甚少。随着孕期越来越多地使用GLP-1，评估其对新生儿的影响至关重要。本研究评估了GLP-1暴露对小鼠母体并发症和新生儿缺陷的影响。怀孕的雌性A/J小鼠在胚胎第1天（EP，早孕）或第15天（E15，晚孕）接受重组GLP-1（rGLP-1；1000 nmol/kg）皮下注射。记录母体和新生儿的体重、形态和死亡率，并进行mRNA测序以分析新生儿组织中的基因表达。rGLP-1暴露后母体体重下降，早期和晚期暴露组出生的幼崽体重均显著减轻。晚期暴露组的幼崽出现皮肤均匀脱落，死亡率显著高于早期暴露组。此外，RT-PCR分析证实了皮肤中选定基因的表达显著增加以及相关的发病机制。对晚期暴露组幼崽的皮肤、大脑、肺和肝脏组织进行RNA测序，结果显示基因表达发生了改变。由于观察到母体体重减轻、新生儿死亡率增加和基因表达改变，孕期应避免使用GLP-1受体激动剂（GLP-1RAs）。
