Plasma Formate Is Greater in Fetal and Neonatal Rats Compared with Their Mothers

Area of Science:

• Biochemistry
• Developmental Biology
• Maternal-Fetal Medicine

Background:

• Formate is a crucial one-carbon unit precursor for purine and thymidylate synthesis, and homocysteine remethylation.
• Understanding formate's role in fetal and neonatal development is essential for metabolic health.

Purpose of the Study:

• To investigate plasma formate concentrations and gene expression related to formate metabolism in fetal, neonatal, and adult rats.
• To elucidate the dynamics of formate production and utilization during pregnancy and early development.

Main Methods:

• Plasma formate levels were quantified using gas chromatography-mass spectrometry (GC-MS).
• Messenger RNA (mRNA) abundance for key metabolic genes was analyzed via quantitative polymerase chain reaction (qPCR).
• Plasma amino acid profiles were determined using high-performance liquid chromatography (HPLC).

Main Results:

• Fetal plasma formate concentrations were significantly higher than maternal levels, and neonatal levels remained elevated before returning to adult concentrations by three weeks.
• Mitochondrial 10-formyl-tetrahydrofolate synthetase (Mthfd1l) and NAD-dependent methylene-tetrahydrofolate dehydrogenase (Mthfd2) mRNA expression were significantly upregulated in the placenta and fetus.
• Genes involved in 10-formyl-tetrahydrofolate (10-formyl-THF) catabolism showed lower expression in fetuses and neonates compared to adults.

Conclusions:

• Formate metabolism is highly active in the placenta and fetuses of pregnant rats.
• These findings highlight the critical role of active formate metabolism in supporting fetal and neonatal development.