Exposome & pregnancy-associated triggers of host immunity and SEX-dimorphic outcomes - the objective of the "exposome & pregnancy-associated triggers of host immunity and SEX-dimorphic outcomes…

The National Institutes of Health Office of the Director awarded Wayne State University a cooperative agreement for $1.5 million on August 1, 2026, under the Trans-NIH Research Support program (CFDA 93.310) to execute the Exposome & Pregnancy-Associated Triggers of Host Immunity and Sex-Dimorphic Outcomes (E-PATHS) program at the C.S. Mott Center for Human Growth and Development.

The award funds research examining how sexual dimorphism influences immune adaptation to environmental stressors during pregnancy and its implications for maternal, paternal, and fetal health outcomes. The program addresses three specific research aims: understanding sex-specific immunological responses of the placenta to outdoor air pollutant benzene and viral infections and their impact on fetal immune development; determining mechanisms by which indoor air pollutants (e-cigarette nicotine and benzoic acid) alter developing lung immune adaptations in a sex-specific manner, resulting in deficient antiviral innate immune responses; and investigating preconception perfluoroalkyl substances (PFAS) exposure in males and resulting effects on maternal immunity and offspring outcomes.

The cooperative agreement runs through July 31, 2031, with place of performance in Detroit, Michigan. Wayne State University's Sponsored Project Administration Division, doing business as Wayne State University Physician Group, is the recipient. The award obligates $1.5 million across the five-year period of performance.

Exposome & pregnancy-associated triggers of host immunity and SEX-dimorphic outcomes - the objective of the "exposome & pregnancy-associated triggers of host immunity and SEX-dimorphic outcomes program (e-paths) at the C.S. Mott center for human growth and development at wayne state university is to enhance our understanding related to the influence of sexual dimorphism on immune adaptation to environmental stressors and its implication on the health of the father, mother and the offspring. Adult sexual dimorphisms observed in the susceptibility to many cancers, autoimmune disorders, and infectious diseases are attributed to differences in the immune system between females and males. Similarly, fetal SEX has been associated with differential risks of perinatal outcomes, including preterm birth and pre-eclampsia. We propose an innovative hypothesis that challenges the current concept about the adaptation of the immune system during pregnancy and hypothesize that immunological responses from the paternal-maternal-placental-fetal tetrad to microbial and environmental stimuli is SEX-specific. The specificity of the response to the environmental stimuli and the SEX of the placental/fetal unit will determine the impact on the immunological development that will translate on tissue and SEX specific differential immune responses on the offspring. We propose the e-paths program to achieve the following overall specific aims: aim 1. To understand the SEX-specific immunological response of the placenta to outdoor air pollutant benzene and viral infections and its impact on the development of the fetal immune system during pregnancy. Aim 2. To determine the mechanism by which indoor air pollutant e-cigarettes' nicotine and benzoic acid alter the developing lung immune adaptations in a SEX-specific manner, resulting in deficient antiviral innate immune responses and increased risk to respiratory viral infections. Aim 3. To investigate preconception PFAS in males and resulting modulation of sperm methylation leading to sexually dimorphic placental programming and intergenerational predisposition to immune mediators of cardiometabolic disease in F1 offspring. Aim 4. To promote career development on the field of sexual dimorphism, with an emphasis on environmental stressors and fetal immune development. Upon successful completion of these aims, the e-paths program will deliver a solid foundation on SEX-specific pre-conception, gestational and developmental immune outcomes following microbial infections and enable future translational research and therapeutic approaches