The effects of direct addition of lead(ii) acetate to a human in vitro model of hematopoiesis recapitulates exposure to lead in utero

Abstract

Metal and heavy metal exposure during pregnancy and early immune system development is a known environmental health concern in the United States and worldwide. Michigan's aging infrastructure has led to disparities in heath equity regarding exposure to lead. Flint, Michigan drew national attention for dangerous lead levels in the community's water sources. However, a 2016 report from the Michigan Department of Health and Human Services confirmed that no Michigan county has more lead-poisoned children than Kent County (Grand Rapids, MI), with a disproportionate number of lead-poisoned youth. Lead exposure during pregnancy has been associated with adverse obstetrical outcomes. Additionally, lead is a known immunotoxicant that easily crosses the placental barrier, and yet little is known about the effects of lead on the human developing immune system. Additionally, international regulatory agencies are moving to adopt new approach methodologies (NAM) for chemical safety assessments and regulatory decision-making. The purpose of the present study was to utilize a previously published NAM, which has been shown to develop cells from the myeloid and lymphoid immune lineages, to determine the effects of lead on human immune development, while confirming these findings with ex vivo human umbilical cord PBMCs exposed to lead in utero. Our results demonstrate that the in vitro approach recapitulates human exposure data and previously published rodent models.

Keywords: CD34; Hematopoiesis; Immune development; Lead.