GLP-1-Mediated Pregnancy and Neonatal Complications in Mice
Rajalakshmi Ramamoorthy, Arianna K. Carden, Hussain Hussain, Brian Zachary Druyan, Ping Ping Chen, Rima Hajjar, Carmen Fernández, Nila Elumalai, Amirah B. Rashed, Karen Young, Anna Rosa Speciale, Emily M. West, Staci Marbin, Bradley Safro, Ian J. Bishop, Arumugam R. Jayakumar, Luis Sanchez‐Ramos, Michael J. Paidas
Abstract
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.