To investigate the correlation between the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and placental cell apoptosis.

Using an external dataset, the impact of MTHFR gene polymorphism on its self-expression was explored. We initially explored placental tissues from 60 pregnant women were collected and divided into MTHFR mutant and wild-type groups. Hematoxylin and eosin staining were used to observe the morphological changes in the placental tissues of the two groups. Tunnel staining was employed to assess the level of apoptosis in placental tissues. Pearson correlation analysis was used to explore the relationship between MTHFR and the expression of apoptosis-related genes.

Expression Quantitative Trait Loci (eQTL) analysis revealed a negative correlation between the C677T gene polymorphism and its expression in 21 of tissues. Clinical sample verification showed a higher incidence of pregnancy complications in the MTHFR mutant group (56.67%,17/30) compared to the wild-type group (26.66%, 8/30) . The apoptosis index in the mutant group (35.82%± 8.45%) was higher than in the wild-type group (22.05%± 6.42%) . In placental tissues, MTHFR expression was positively correlated with the anti-apoptotic gene BCL2L2 (r = 0.211) and negatively correlated with the pro-apoptotic gene BAK1 (r = -0.182) .

MTHFR C677T gene polymorphism may lead to downregulation of MTHFR expression, and be correlated to placental cell apoptosis, and potentially contributing to adverse pregnancies.