Genetic expression of NKX2-5 gene among first trimester pregnancy loss

Abstract

First-trimester pregnancy loss is a serious public health problem, affecting both physical and mental well-being. Occurring in 10–15 % of clinically recognized pregnancies, it remains a critical issue in reproductive health. Genetic factors impacting fetal development and maternal inflammatory responses are linked to early pregnancy loss. This case-control study included 120 participants: 60 cases (including maternal samples for evaluating inflammatory markers and their products of conception or terminated fetuses without normal cardiac activity or suspected congenital heart defects for the evaluation of NKX2–5 gene expression) and 60 healthy mothers having one or two live children without any congenital heart defects as controls. Inflammatory markers CRP and IL-6 were measured using ELISA kits. Gene expression of NKX2–5 was quantified by real-time PCR after RNA extraction from products of conception or terminated fetuses, cDNA synthesis, and amplification using specific primers. Relative expression was calculated using the 2^(-ΔΔCt) method. The findings revealed significantly higher CRP and IL-6 levels in cases than controls (p < 0.001) and changes in NKX2–5 expression. The results indicate a significant increase in NKX2–5 expression in products of conception from women with early pregnancy loss compared to those with healthy pregnancies (p < 0.05). Increased maternal levels of TSH were also revealed to be an independent predictor for early abortion (OR = 3.57, p = 0.004). Our findings suggest that NKX2–5 gene deregulation and inflammation in the maternal compartment can play a role in early pregnancy loss as future candidate targets for both diagnostic and treatment intervention.