Intrinsic Sexual Dimorphism in the Placenta Determines the Differential Response to Benzene Exposure
Year: 2022
Type: article
Abstract: Maternal immune activation (MIA) by environmental challenges is linked to severe developmental complications, such as neurocognitive disorders, autism, and even fetal/maternal death. Benzene is a major toxic compound in air pollution that affects the mother as well as the fetus and has been associated with reproductive complications. However, it is poorly understood how benzene induces these complications. Our objective was to elucidate whether benzene exposure during gestation triggers MIA and its impact on fetal development. We established a full body inhalation mouse model for maternal benzene exposure that mimics clinical phenotypes observed in human populations. Here, we report that benzene exposure during pregnancy leads MIA associated with increased fetal resorptions, abnormal placenta development, and low birth weight. More importantly, we demonstrate the existence of a sexual dimorphic response to benzene exposure in male and female placentas. In the male placenta, the transcriptome changes reveal a more immunologically relevant profile, while females have a metabolically related profile. Furthermore, our data provide evidence that the sexual dimorphic response could be a consequence of inherent differences between male and female placenta, indicating the significant difference between sexes in placental processes, in both humans and mouse. These data provide crucial information on the origins or sexual dimorphism and how exposure to environmental factors can have a differential impact on the development of male and female offspring.Funding Information: This work was supported in part by NIH grant NIAID 5R01AI145829-03 (GM), R00ES028734-01A1 (MP), CURES: 5 P30 ES020957, ECHO: 5 UH3 OD023285, S10: OD025170 (DR), NIEHS R01ES033171 (MS). We acknowledge the assistance of the Wayne State University Proteomics Core that is supported through NIH grants P30 ES020957, P30 CA022453 and S10 OD030484.Declaration of Interests: The authors have declared that no conflict of interest exists.Ethics Approval Statement: All experimental procedures were in accordance with National Institutes of Health guidelines (NIH Publication No. 85–23, revised 1996), with approval by the Animal Care and Use Committee at Wayne State University School of Medicine (Assurance Number A3310-01).
Source: iScience
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,000
Funders: Wayne State University, School of Medicine, Wayne State University, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Environmental Health Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1233667601, G1906908682, NovaSeq Shared Instrumentation Grant for Wayne State University, Mechanisms of trophoblast-induced immune modulation, G3642527456, Center for Urban Responses to Environmental Stressors (CURES), G5022595634, G5143905934, TMAO is a biomarker of dioxin-like pollutant exposure and cardiometabolic disease, G5967209050, Prenatal Exposures and Child Health Outcomes 2: Increasing ECHO Urban and Rural Diversity, Orbitrap Tribrid Mass Spectrometer for Wayne State Proteomics, G7931923669, G9000119117, G9000129347, G9000145461, Prenatal Exposures and Child Health Outcomes 2: A Statewide Study of Michigan Families, Benzene exposure promotes neuroinflammation and metabolic dysregulation, Impact of benzene-induced MIA on fetal T cell development, CANCER CENTER SUPPORT GRANT, Center for Leadership in Environmental Awareness and Research
OpenAlex ID: W4322491877