Sex-specific adaptations in placental mitochondrial biogenesis and function in babies born with critical congenital heart disease
Abstract
Congenital heart disease (CHD) is the leading cause of birth defects; most critical CHD (cCHD) newborns will develop neurodevelopmental disorders. Abnormal placental development may be involved, as genetics explains only 30% of sporadic CHD cases. Growing evidence suggests that placental dysfunction may result in heart and brain defects, as it shares a common early development. We hypothesized that newborns with cCHD exhibit sex-specific alterations in placental mitochondrial biogenesis and function, which may affect the fetal growth trajectory. Term placenta and paired umbilical cord (UC) blood were collected at birth from cCHD (n = 16) and matched control (n = 20) neonates. Mitochondrial lipid complex (phosphatidic acid (PA), phosphatidylglycerol (PG), and cardiolipin (CL)), acylcarnitine metabolites, and organic acids were determined in placenta by LC-MS/MS. Gene expressions of enzymes involved in mitochondrial biogenesis, dynamics, and lipid pathways were measured in the placenta by RT-qPCR. Placental protein expressions of β-oxidation and OXPHOS were determined by western blot. Mitochondrial dynamics were reduced in cCHD placentas, particularly in male infants. Long-chain acylcarnitine (LC-acar) metabolites decreased in female cCHD placentas and increased in males, while they increased in both sexes in UC plasma. Malonate levels increased in cCHD placentas, affecting the TCA cycle. CL de novo synthesis was dysregulated in the cCHD placentas, though CL concentrations were similar in both groups. The cCHD placenta may compensate for cardiac defects in a potential sex-dependent manner, leading to an accumulation of LC-acar in the UC plasma. Placental mitochondrial adaptation to metabolic needs may have cardioprotective and neuroprotective effects.
Related
- Lactate promotes mitochondrial biogenesis and fusion via GPR81 to enhance synaptic plasticity-related protein expression in hippocampal cells
- PPR9 mediates mitochondrial nad transcript maturation required for complex I biogenesis and early plant development in Arabidopsis.
- Astragalus Polysaccharide Enhances Mitochondrial Biogenesis and Function in Cardiomyocytes Through AMPK Activation.
- Metabolically reprogrammed blastoids from totipotent-like stem cells exhibit enhanced tissue-specific organ-like development and placental formation
- Lineage-specific and gestational age–dependent DNA methylation programming orchestrates human placental development
BibTeX
@article{demonceaux2026sexspecific,
title = {{Sex-specific adaptations in placental mitochondrial biogenesis and function in babies born with critical congenital heart disease}},
author = {Marie Demonceaux and Alban-Elouen Baruteau and Chloé Cloteau and Mathilde Gourdel and Bénédicte Romefort and Nadir Benbrik and Morgane Vincke and Garance Devarenne and Norbert Winer and Véronique Ferchaud-Roucher},
journal = {Clinical Science},
year = {2026},
month = nov,
doi = {10.1042/cs20260162},
url = {https://hal.inrae.fr/hal-05855932v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Sex-specific adaptations in placental mitochondrial biogenesis and function in babies born with critical congenital heart disease
AU - Marie Demonceaux
AU - Alban-Elouen Baruteau
AU - Chloé Cloteau
AU - Mathilde Gourdel
AU - Bénédicte Romefort
AU - Nadir Benbrik
AU - Morgane Vincke
AU - Garance Devarenne
AU - Norbert Winer
AU - Véronique Ferchaud-Roucher
PY - 2026
DA - 2026/11/07
JO - Clinical Science
DO - 10.1042/cs20260162
UR - https://hal.inrae.fr/hal-05855932v1
AB - Congenital heart disease (CHD) is the leading cause of birth defects; most critical CHD (cCHD) newborns will develop neurodevelopmental disorders. Abnormal placental development may be involved, as genetics explains only 30% of sporadic CHD cases. Growing evidence suggests that placental dysfunction may result in heart and brain defects, as it shares a common early development. We hypothesized that newborns with cCHD exhibit sex-specific alterations in placental mitochondrial biogenesis and function, which may affect the fetal growth trajectory. Term placenta and paired umbilical cord (UC) blood were collected at birth from cCHD (n = 16) and matched control (n = 20) neonates. Mitochondrial lipid complex (phosphatidic acid (PA), phosphatidylglycerol (PG), and cardiolipin (CL)), acylcarnitine metabolites, and organic acids were determined in placenta by LC-MS/MS. Gene expressions of enzymes involved in mitochondrial biogenesis, dynamics, and lipid pathways were measured in the placenta by RT-qPCR. Placental protein expressions of β-oxidation and OXPHOS were determined by western blot. Mitochondrial dynamics were reduced in cCHD placentas, particularly in male infants. Long-chain acylcarnitine (LC-acar) metabolites decreased in female cCHD placentas and increased in males, while they increased in both sexes in UC plasma. Malonate levels increased in cCHD placentas, affecting the TCA cycle. CL de novo synthesis was dysregulated in the cCHD placentas, though CL concentrations were similar in both groups. The cCHD placenta may compensate for cardiac defects in a potential sex-dependent manner, leading to an accumulation of LC-acar in the UC plasma. Placental mitochondrial adaptation to metabolic needs may have cardioprotective and neuroprotective effects.
SN - 0143-5221
SN - 1470-8736
ER -