A meta-analytic review of early inflammatory exposure and intrinsic mechanochemical sensing

Intrinsic mechanochemical sensing—the ability of developing and regenerating tissues to perceive internal bioelectric, mechanical, and metabolic cues—plays a central role in both morphogenesis and lifelong tissue homeostasis. Disruptions in this sensing network are increasingly recognized as key contributors to congenital anomalies and impaired repair, yet their origins remain unclear. One plausible developmental risk factor is exposure to inflammatory stress during early ontogeny. Here we present a meta-analytic review examining the association between early inflammatory exposure and distinct facets of intrinsic mechanochemical sensing. Using random-effects models, we synthesized data from 17 animal and organoid studies that quantified the impact of prenatal or early postnatal cytokine challenge on sensing precision, sensitivity, integration, and signal fidelity. Across studies we found no consistent association between early inflammatory exposure and sensing precision, sensitivity, or integration. However, a history of inflammatory challenge—particularly chronic, low-grade cytokine exposure—was reliably linked to reduced signal fidelity, a dimension reflecting the confidence with which tissues translate internal cues into patterning decisions. These findings suggest that early adverse inflammatory environments may erode the foundational feedback loops governing tissue pattern memory, with potential long-term consequences for developmental robustness and regenerative competence.