Deciphering the trace metal-inflammation axis in the pathophysiology of recurrent pregnancy loss.

BACKGROUND Recurrent Pregnancy Loss (RPL) is a multifactorial reproductive disorder influenced by genetic, immunological, and metabolic disturbances. Altered trace element and heavy metal levels increasingly contribute to oxidative stress, inflammation, and impaired methylation, potentially affecting pregnancy outcomes.

METHODS A case-control study was conducted including RPL patients (n = 48) and healthy controls (n = 48). Serum levels of Cu, Zn, Pb, Fe, Cr, Se, Cd, As, and Mg were assessed using Atomic Absorption Spectrophotometry. Inflammatory and metabolic biomarkers MMP-2, TNF-α, Vitamin B12, Folate, and Homocysteine measured using ELISA. Molecular docking analyses (Auto Dock Vina) performed to determine the binding affinities of the trace metals with TNF-α, Vitamin B12, and Homocysteine.

RESULTS Cu, Cr, Mg, and Pb levels were significantly elevated in RPL patients (p < 0.01), whereas Zn and Fe were markedly lower (p < 0.0001). No significant differences were observed for Se, Cd, and As. RPL patients exhibited higher MMP-2 and TNF-α levels (p = 0.0001 each) and reduced Vitamin B12 (p = 0.0364), while homocysteine levels were unexpectedly decreased (p = 0.006). Docking analysis revealed strong Pb²⁺ affinity for TNF-α (-12.58 kcal/mol), suggesting pro-inflammatory stabilization, while Cu²⁺ demonstrated high affinity for Vitamin B12 (-8.5 kcal/mol).

CONCLUSION The study findings indicate that dysregulated trace element patterns specifically elevated Pb²⁺, Cu²⁺, and Cr³⁺ with reduced Zn²⁺ and Fe²⁺ may disrupt inflammatory, metabolic, and methylation pathways in RPL. High-affinity metal-protein interactions further support their potential diagnostic and therapeutic relevance.