α-MSH positively influences fetal heart rate variability in relation to maternal metabolic state

Objective: Alpha-melanocyte stimulating hormone (α-MSH), produced by pro-opiomelanocortin neurons in the hypothalamus and pituitary, plays a key role in regulating energy balance and appetite. During pregnancy, α-MSH levels increase and have been positively associated with maternal insulin sensitivity. Previous studies have linked circulating α-MSH to alterations in cardiac function. This study aimed to explore the relationship between maternal α-MSH and fetal heart rate variability (fHRV) parameters, while accounting for maternal metabolic factors such as BMI and fasting glucose.

Methodology: Maternal and fetal data were collected as part of the PREG study (clinical trial identifier: NCT04270578). fHRV was assessed in both time and frequency domains using 122 magnetocardiography recordings from 63 fetuses at 27–35 weeks of gestational age. Maternal serum α-MSH and other blood parameters were measured via ELISA. Principal component analysis (PCA) was applied to fetal HRV and maternal metabolic parameters, retaining the first n components based on the scree plot's inflection point. Component scores were calculated and correlated with α-MSH levels. In addition, α-MSH was applied to primary fetal cardiomyocytes from C57BL6N mice and beat frequency was measured 6 and 24 hours post application in culture.

Results: Three principal components (PCs) were identified, explaining 49.5% of the total variance. PC1 (22.5%) showed strong positive loadings for fHRV parameters and negative loadings for maternal metabolic factors like BMI. PC1 was positively correlated with α-MSH (p<0.0001). PC2 (18.7%) had strong positive loadings for BMI, fasting glucose, and C-peptide, with negative loadings for insulin sensitivity, and was negatively correlated with α-MSH (p<0.0001). PC3 (8.3%), while explaining relations among maternal metabolic factors, was not associated with α-MSH (p>0.05). Primary cultured cardiomyocytes show a direct effect of α-MSH application, reducing beat frequency in culture.

Conclusions: In humans, higher maternal α-MSH levels were associated with higher fHRV, a marker of fetal well-being, and lower maternal BMI. Conversely, lower α-MSH levels were linked to poorer maternal metabolic health, characterized by higher BMI, fasting glucose, and C-peptide levels, and lower insulin sensitivity. In mice, primary cardiomyocytes culture could show direct effects of α-MSH application on the cardiomyocytes, strengthening the direct link between α-MSH levels and cardiac function. These findings highlight the potential role of maternal α-MSH and metabolic health in fetal development.

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Artikel online veröffentlicht:
28. Mai 2025