Profile integration expression of microRNAs and mRNAs for reconstruction of gene regulatory networks in human Sertoli cells exposed to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)

• Grant number: 15/16863-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: April 01, 2016
• End date: July 31, 2016
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Wellerson Rodrigo Scarano
• Grantee: Mariana Antunes Ribeiro
• Supervisor: Stephen Andrew Krawetz
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: Wayne State University (WSU), United States
• Associated to the scholarship: 13/12154-2 - Overall micro-RNA expression profile in human Sertoli cells (HSEC) after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), BP.DR

Abstract

Male fertility and spermatogenesis process are directly related to the ability of Sertoli cells to produce factors associated with germ cells development. Only the Sertoli cells have receptors for FSH and testosterone, and therefore these cells are the major spermatogenesis regulators. Studies suggest that 60-70% male infertility cases are considered idiophatic, since the molecular mechanisms involved in spermatogenesis are still unknown. Recent studies report that regulatory RNA molecules encoded by the genome, such as microRNAs (miRNAs) are able to modulate testicular function during spermatogenesis and their altered expression may be involved with various factors of male infertility. miRNAs may play an important role in response to xenobiotics and chemical consequences to health, causing diseases. An important group of organic compounds with high toxic protencial are the dioxins, having as its most representative 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Experimental models of exposure (mice) demonstrated that TCDD causes low sperm count and delayed puberty. Thus, this study aims at correlating the action of TCDD compound on the human Sertoli cells and its possible action in the expression profile of miRNAs and mRNA and possible identify networks regulation and molecular pathways involved with fewer nephrons found in this model. In this context, the internship in the laboratory of Dr. Krawetz aims to: identify the global expression profile of mRNA transcripts (transcriptome) and microRNAs (microRNome) in the human Sertoli cells; identify the influence of TCDD on the expression profile of the transcriptome and microRNoma in Sertoli cells and build protein interaction networks between proteins encoded by target genes potentially regulated by microRNAs and identify altered molecular pathways related to spermatogenesis. (AU)