Monocyte chemoattractant Protein-1 (MCP-1) decreases mineralization of the villous stroma in the macaque placenta

Abstract

Placental insufficiency occurs when a fetus does not receive adequate oxygen and/or nutrients, leading to adverse pregnancy outcomes (APOs). Increased leukocyte density has been observed in placental inflammatory lesions, resulting in placental insufficiency and APOs. MCP-1 is a chemokine associated with inflammatory disease, that actively attracts leukocyte populations. We investigated the effects of a supraphysiological MCP-1 injection into the maternal-fetal interface (MFI), using the macaque pregnancy model. METHODS: A placental injection of MCP-1 or saline was administered to macaques between gestational day (GD) 100-105, along the MFI. Acute effects (n = 2) and full-term effects (n = 8) were studied. Full-term pregnancies had maternal placental blood perfusion measured via dynamic contrast enhanced MRI, before and after injection. Fetoplacental tissues were collected near term (GD 155). Placental histopathology was investigated, along with decidual immune populations, MRI-defined maternal blood metrics, and fetal biometrics. RESULTS: Acutely, increased leukocyte clustering and decreased mineralization were observed within the villous stroma of MCP-1-treated cotyledons. Decreased villous mineralization with MCP-1 injection was also noted in full-term pregnancies, along with a proportional increase in decidual dendritic cells. MRI placental analysis revealed a trend of increased maternal blood flow and reduced fill time after MCP-1 injection, alongside healthy fetal biometrics. DISCUSSION: Although MCP-1 is typically associated with inflammation and tissue pathology, our study demonstrates that supraphysiological MCP-1 levels led to increased leukocyte clustering and reduced mineralization in the villous stroma, without impairing maternal blood perfusion or fetal growth. These findings suggest a beneficial role for MCP-1 in the context of placental function.

Part of CIRS Nexus · Curated by Lauren Lowenstein, The Biotoxin Lady