Effect of Multiparity on Pregnancy-Induced Islet Adaptation and Cellular Transdifferentiation

Area of Science:

• Endocrinology
• Cell Biology
• Reproductive Biology

Background:

• Pregnancy reversibly increases pancreatic islet and beta-cell mass.
• The impact of multiple pregnancies on these adaptations is not well understood.

Purpose of the Study:

• To investigate islet and beta-cell adaptations during multiple pregnancies (primi-, bi-, and tri-parity).
• To explore the role of cellular plasticity and transdifferentiation in maintaining beta-cell mass across gestations.

Main Methods:

• Utilized transgenic mice (Ins1^Cre/+;Rosa26-eYFP and Glu^CreERT2;Rosa26-eYFP) for beta- and alpha-cell lineage tracing.
• Assessed islet morphology, cell proliferation, apoptosis, and transdifferentiation in response to varying parity.

Main Results:

• All pregnant mice showed increased islet and beta-cell areas with reduced apoptosis and increased proliferation.
• Beta-cell proliferation decreased with higher parity but remained elevated compared to controls.
• Alpha-cells also increased in size and survival; alpha- to beta-cell transdifferentiation was enhanced in multiparity, suggesting a key role in beta-cell expansion.

Conclusions:

• Reduced beta-cell proliferation in multiparity is compensated by increased islet cell plasticity.
• Enhanced alpha- to beta-cell transdifferentiation and neogenesis contribute to sustained beta-cell mass expansion across multiple pregnancies.