Microrna-290 regulates maternal-fetal nutrient exchange during neural tube closure

The National Institute of Child Health and Human Development awarded Baylor College of Medicine $149,190 on January 1, 2026, to conduct research on microRNA-290's role in regulating maternal-fetal nutrient exchange during neural tube closure under the Child Health and Human Development Extramural Research program (CFDA 93.865).

The research investigates how microRNA-290 expressed in extraembryonic tissues, including the yolk sac, affects nutrient transport to embryos during early pregnancy neurulation. The project examines the mechanisms by which loss of microRNA-290 combined with maternal metabolic dysregulation—modeled through pregestational hyperglycemia—increases neural tube defects and cellular stress in the yolk sac and placenta. Preliminary metabolic analysis shows decreased folic acid reaching embryos from hyperglycemic dams, along with reduced antioxidant glutathione and elevated methyl donor SAM in affected embryos. The research focuses on one-carbon metabolism pathways that provide methyl groups for lipid synthesis, DNA and protein methylation, and antioxidant production. The work is performed at Baylor College of Medicine in Houston, Texas, with a period of performance from January 1, 2026, through August 13, 2027. This is a project grant, the standard assistance type for individual research proposals within NICHD's extramural portfolio.

Abstract

Neural tube defects (NTDS) are among the most common and severe birth defects, affecting over 300,000 infants worldwide each year. NTDS are often lethal and, if not, lead to devastating health consequences and early childhood mortality due to the improper development of the brain and /or spinal cord. Prevention of NTDS is also challenging because primary neurulation begins in the third to fourth week of pregnancy, often before a woman even knows they are pregnant. During this early pregnancy timepoint, the yolk SAC acts as the interface between the maternal and fetal environments. IT supplies the growing embryo with the correct balance of metabolites for successful growth and development. Microrna-290 is expressed exclusively in extraembryonic tissues, including the yolk SAC, and when knocked out, leads to a partially penetrant NTD phenotype. However, with pregestational hyperglycemia, as a model of maternal metabolic dysregulation, loss of MIR-290 leads to increased incidences of neural tube closure defects and cellular stress in both the yolk SAC and placenta. Additionally, preliminary metabolic analysis of the yolk SAC and cranial region of E10.5 embryos reveals decreased folic acid is reaching the embryos from hyperglycemia dams. Folic acid is an essential vitamin supplied from the maternal diet, and deficiency is known to contribute to NTDS; however, precisely how folate prevents NTDS is unclear. We also found decreases in antioxidant glutathione and increased methyl donor SAM in the MIR-290 KO embryos, likely exacerbating the metabolic dysregulation caused by maternal stress. Folic acid, SAM, and glutathione are all part of one-carbon metabolism, a series of interlocking, essential metabolic cycles that provide methyl groups for numerous cell functions, including lipid synthesis. DNA and protein methylation, and production of antioxidants. Therefore, we hypothesize that MIR-290 protects extraembryonic tissues from metabolic dysregulation by regulating one-carbon metabolism. We aim to build off our preliminary metabolic results to establish a mechanism by which defects in extra-embryonic tissue metabolism drive transcriptional changes in the neuroepithelial cells, impeding neural tube closure. We plan to investigate how maternal metabolic stress impacts the yolk SAC function, leading to impaired fetal central nervous system development, and to identify strategies that can be implemented before and during the earliest pregnancy time points.