INTRODUCTION: Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, widely used in the treatment of diabetes and obesity. Despite its increasing clinical use, limited data exist regarding the effects of maternal semaglutide exposure during pregnancy on offspring development. Manufacturers recommend discontinuing therapy two months before a planned pregnancy, yet nearly 45% of pregnancies are unplanned and detected in the first trimester, leading to continued treatment in early pregnancy.

AIM(S): This study aimed to evaluate the effects of maternal semaglutide exposure during pregnancy on early offspring development.

METHOD(S): Female Swiss albino mice received increasing doses of semaglutide or saline prior to mating and throughout 14 days of pregnancy. Early offspring development was evaluated through developmental milestones tests. Observations were conducted daily from day 3 to day 14 of pup life. The analyzed key milestones included: pinnae detachment (ear unfolding), ear opening, eye opening, fur development, crawling, transition from crawling to walking. These developmental markers reflect somatic and neuromotor maturation during early life.

RESULTS: Offspring of semaglutide-treated mothers demonstrated delayed timing of selected developmental milestones. Eye opening and ear opening occurred later compared to control, with the most pronounced differences observed on postnatal day 13. In contrast, motor development analysis revealed earlier onset of walking in offspring prenatally exposed to semaglutide, with significant differences also noted on 13 PND. No marked differences between groups were observed in the remaining milestones (pinnae detachment, fur development, crawling, transition).

CONCLUSIONS: These results suggest that maternal semaglutide exposure may modulate the pace of early neurological and motor development in offspring, delaying sensory maturation while accelerating locomotor development, highlighting the need for further studies on prenatal GLP-1 agonist exposure.

FINANCIAL SUPPORT: National Science Centre of Poland, grant number 2023/51/B/NZ7/02360 and statutory fund of IP PAS.