Intrinsic sexual dimorphism in the placenta determines the differential response to benzene exposure
Anthony Maxwell,
Nicholas Adzibolosu,
Anna Hu,
Yuan You,
Paul M. Stemmer,
Douglas M. Ruden,
Michael C. Petriello,
Marianna Sadagurski,
Lucas K. Debarba,
Lisa Koshko,
Jayanth Ramadoss,
Annie Thy Nguyen,
Darby Richards,
Aihua Liao,
Gil Mor,
Jiahui Ding
Affiliations
Anthony Maxwell
C.S Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
Nicholas Adzibolosu
C.S Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
Anna Hu
C.S Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
Yuan You
C.S Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
Paul M. Stemmer
Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, USA
Douglas M. Ruden
C.S Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
Michael C. Petriello
Institute of Environmental Health Sciences and Department of Pharmacology, Wayne State University, Detroit, MI, USA
Marianna Sadagurski
Department of Biological Sciences, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA
Lucas K. Debarba
Department of Biological Sciences, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA
Lisa Koshko
Department of Biological Sciences, Integrative Biosciences Center, Wayne State University, Detroit, MI, USA
Jayanth Ramadoss
C.S Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA
Annie Thy Nguyen
School of Medicine, Wayne State University, Detroit, MI, USA
Darby Richards
School of Medicine, Wayne State University, Detroit, MI, USA
Aihua Liao
Institute of Reproductive Health, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China
Gil Mor
C.S Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA; Corresponding author
Jiahui Ding
C.S Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA; Corresponding author
Summary: 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. Our objective was to elucidate whether benzene exposure during gestation triggers MIA and its impact on fetal development. We report that benzene exposure during pregnancy leads MIA associated with increased fetal resorptions, fetal growth, and abnormal placenta development. Furthermore, we demonstrate the existence of a sexual dimorphic response to benzene exposure in male and female placentas. The sexual dimorphic response is a consequence of inherent differences between male and female placenta. 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.
