A mixture of organophosphate esters sex-specifically impacts monocyte–macrophages in Sprague-Dawley rats

Exposure to individual organophosphate esters (OPEs) has been linked to immune dysfunction. However, the effect of OPEs as environmentally relevant mixtures on the immune system remains poorly understood. This study examines how parental exposure to an OPE mixture impacts the immune status of Sprague-Dawley rats and their offspring. Sprague-Dawley rats were fed a control or OPE-supplemented diet containing 13 OPEs detected in >85% of Canadian homes. Only male offspring of OPE-exposed animals showed a significant reduction in CD43lowHis48hi splenic monocyte-macrophages. There were no significant changes in CD43lowHis48hi splenic monocyte-macrophages in the F0 generation or female offspring. However, the OPE mixture significantly altered serum cytokine levels in both sexes and generations, with females and offspring experiencing more pronounced changes. Notably, female progeny had elevated levels of chemokines associated with monocyte recruitment. In vitro follow-up studies revealed that the OPE mixture delays monocyte-to-macrophage transition and monocyte migration in both sexes. These results indicate that an environmentally relevant OPE mixture disrupts immune function by affecting monocyte recruitment and differentiation but does not reveal clear sex differences. However, when combined with cytokine findings, these results support a hypothesis that OPE exposure causes male-specific decreases in CD43lowHis48hi monocyte-macrophages that are absent in females due to compensatory inflammation. These studies demonstrate that an environmentally relevant mixture of OPEs can alter basal immune status in the offspring of exposed animals. This work will be useful for risk assessment studies and regulations protecting human health.