Maternal obesity and inadequate gestational weight gain disrupts placental dopaminergic signaling: impact on infant neurodevelopment.

INTRODUCTION

The maternal-fetal axis plays a critical role in human development. Obesity during pregnancy may be associated with alterations in this axis, particularly the placental dopaminergic signaling, potentially affecting infant neurodevelopment.

METHODS

Participants (n=35) from the OBESO cohort (Mexico City) were classified by pregestational BMI as normal weight (n=20) or obese (n=15). Clinical and anthropometric variables of the mother-infant dyads were recorded. Neurodevelopment was evaluated in one-month-old infants using the Bayley-III Scales and classified as normal or altered (score ≤7 in any domain). Placental dopamine (DA) concentrations were quantified by ELISA and correlated with neurodevelopmental status. A subset of samples was analyzed by Western blot to explore the expression of key dopaminergic components: tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT), vesicular monoamine transporter 2 (VMAT2), organic cation transporter 3 (OCT3), dopamine transporter (DAT), and dopamine receptor D2 (DRD2).

RESULTS

Reduced placental DA concentrations, together with altered expression of key dopaminergic elements characterized by increased COMT and DAT, and decreased VMAT2, were observed in association with maternal obesity, inadequate gestational weight gain, and altered infant neurodevelopment.

CONCLUSIONS

This study provides exploratory evidence that maternal obesity and inadequate GWG may be associated with early alterations in the intrauterine metabolic and neuroendocrine environment, including changes in the placental dopaminergic system. Differences in the expression of COMT, DAT, and VMAT2, together with lower placental DA concentrations, which may be linked to early neurodevelopmental variability in infants. Overall, the results suggest a potential relationship between maternal metabolic status and placental neuroendocrine pathways, warranting further investigation in larger and longitudinal studies.