Can the toxicity of Di(2-ethylhexyl) phthalate (DEHP) on the male reproductive tract be altered by the birth pathway due to changes in the intestinal microbiota and its systemic impacts in the long term?

• Grant number: 21/08127-6
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2022
• End date: March 31, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Juliana Elaine Perobelli
• Grantee: Juliana Elaine Perobelli
• Host Institution: Instituto do Mar (IMar). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• Associated researchers: Maria Christina Werneck de Avellar

Abstract

Recently, the relationship between the metabolization of environmental pollutants and the mammalian gut microbiota profile, capable of altering the activity, distribution and half-life of these xenobiotics has been described. It is known that the gut microbiota matures over the first years of the child's life, being the birth pathway, if vaginal or cesarean, the main factor interfering in this process. Worldwide, elective cesarean rates are far above those recommended by the World Health Organization, with Brazil being the second country in this ranking. For a better understanding of this issue, we propose a preclinical trial to investigate the influence of the birth pathway on the toxicity of the pollutant di(2-etilhexil)phthalate in the male reproductive system of male Wistar rats exposed for 65 days. We hypothesize that the gut microbiota installed on the first years of life is impacted by the cesarean section and influences the establishment of reproductive tissue microbiotas, as well as causes persistent modulation of the host's immunological and physiological profile; these alterations, in turn, would lead to a greater vulnerability of the individual to environmental pollutants, especially regarding the toxic effects of these compounds on the morphological and functional integrity of male reproductive organs, important targets of pollutants. In addition to the central aim, the proposed study will allow advancing on questions with translational relevance, such as (i) the long-term effects of the birth pathway on the gut microbiota; (ii) the long-term impact on the microbiota of reproductive tissues, (iii) the long-term effects of the birth pathway on immunological profile of the animals; (iv) the long-term effects of the birth pathway on morphophysiological profile of the reproductive tissues; thus, opening possibilities for new studies and mitigation strategies for these impacts. (AU)