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GLP-1-Mediated Pregnancy and Neonatal Complications in Mice

Rajalakshmi Ramamoorthy1, Arianna K Carden2, Hussain Hussain3

  • 1Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA.

Journal of Developmental Biology
|August 22, 2025
PubMed

Insights

Glucagon-like peptide 1 (GLP-1) exposure during pregnancy led to maternal weight loss and significant neonatal complications, including weight loss and increased mortality. These findings suggest GLP-1 receptor agonists should be avoided during gestation.

Area of Science:

  • Endocrinology
  • Developmental Biology
  • Toxicology

Background:

  • Glucagon-like peptide 1 (GLP-1) is a crucial hormone with known physiological roles.
  • Its effects on pregnancy outcomes and neonatal development are not well-established.
  • GLP-1 administration during pregnancy is increasing, necessitating safety assessments.

Purpose of the Study:

  • To investigate the impact of GLP-1 exposure on maternal health and neonatal development in a mouse model.
  • To identify potential risks associated with GLP-1 administration during different stages of pregnancy.

Main Methods:

  • Pregnant A/J mice received subcutaneous recombinant GLP-1 (rGLP-1) injections on embryonic day 1 or day 15.
  • Maternal and neonatal parameters including body weight, morphology, and mortality were monitored.
  • Gene expression analysis using mRNA sequencing and RT-PCR was performed on neonatal tissues.

Main Results:

  • Maternal weight loss was observed following rGLP-1 exposure.
  • Neonatal pups from both early and late exposure groups exhibited significant weight reduction.
  • Late pregnancy exposure resulted in uniform skin detachment and a markedly higher mortality rate in pups.
  • Altered gene expression patterns were identified in neonatal skin, brain, lung, and liver tissues.

Conclusions:

  • GLP-1 exposure during pregnancy can induce adverse maternal and neonatal outcomes.
  • Significant risks, including increased neonatal mortality and developmental defects, are associated with late-pregnancy GLP-1 administration.
  • GLP-1 receptor agonists (GLP-1RAs) are not recommended for use during pregnancy due to observed adverse effects.

Keywords:
A/J miceGlucagon-like peptide 1gene sequencingneonatal complicationspregnancy

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