Human supraphysiological gestational weight gain and fetoplacental vascular dysfunction

Area of Science:

• Obstetrics and Gynecology
• Maternal-Fetal Medicine
• Cardiovascular Physiology

Background:

• Maternal obesity and excessive gestational weight gain are linked to adverse pregnancy outcomes, including cardiovascular disease and neonatal complications.
• Understanding the impact of supraphysiological gestational weight gain (spGWG) on fetoplacental endothelial function is crucial for improving neonatal health.

Purpose of the Study:

• To investigate whether supraphysiological gestational weight gain (spGWG) leads to human fetoplacental endothelial dysfunction.
• To assess the effects of spGWG on fetoplacental vascular reactivity in women with normal prepregnancy weight.

Main Methods:

• Human umbilical vein endothelial cells (HUVECs) and umbilical vein rings were isolated from women with physiological (pGWG) or supraphysiological (spGWG) gestational weight gain.
• Vascular reactivity to insulin was measured in vein rings using wire myography.
• Endothelial nitric oxide synthase (eNOS) expression and phosphorylation, and adenosine transport via human equilibrative nucleoside transporter 1 (hENT1) were analyzed in HUVECs.

Main Results:

• spGWG was associated with reduced nitric oxide synthase (NOS) activity-dependent vasodilation and lower eNOS expression in umbilical vein rings.
• Maximal adenosine transport activity was reduced in HUVECs from the spGWG group, despite increased hENT1 expression.
• Chlorpromazine (CPZ) enhanced hENT1-mediated adenosine transport and membrane accumulation only in cells from the pGWG group.

Conclusions:

• Supraphysiological gestational weight gain in normal-weight women impairs fetoplacental vascular reactivity.
• The observed endothelial dysfunction is attributed to downregulated eNOS activity and impaired adenosine transport in HUVECs.
• Maternal spGWG poses a risk to fetoplacental endothelial function, and interventions targeting these alterations may improve neonatal outcomes.