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Methylation pattern of the imprinting controlling regions and expression of the H19 and IGF-2 genes and androgenic response in human Sertoli cells after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TDCC)


Infertility affects 10-15% of couples on reproductive age and male factor may be responsible for 30-50% of cases. Male fertility and the spermatogenesis process are directly related to the ability of Sertoli cells to produce factors for the development of germ cells. Only Sertoli cells have receptors for testosterone and FSH, and therefore, these cells are the main regulators of spermatogenesis. Studies suggest that 60-70% of male infertility cases are considered idiophatic, once the molecular mechanisms involved in spermatogenesis are still unknown. Recent studies report that oligozoospermic men showed an alteration of the DNA methylation pattern in the sperm, specifically in the regions that control the geneexpression of genes regulated by imprinting, H19 and IGF2. Largely responsible for changing the methylation pattern of these genes are environmental factors, specially organic ompounds with high toxicity, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Experimental models of exposure (mice) showed that TCDD causes low sperm count and delayed puberty. Thus, this study aims to correlate the action of the compound TCDD on human Sertoli cells (*in vitro*) and its possible deleterious effects in controlling imprinting regions (ICRs) of *H19* and *IGF2* and their expressions, which can interfere in the spermatogenic process. Moreover, once the androgen control is performed by Sertoli cells, we intend to evaluate the expression of androgen receptor and NRF-2 molecule (cell stress) to the action of TCDD in order that it can act in different molecular targets in the promotion of issues related to infertility. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RIBEIRO, MARIANA ANTUNES; DOS REIS, MARIANA BISARRO; DE MORAES, LEONARDO NAZARIO; BRITON-JONES, CHRISTINE; RAINHO, CLAUDIA APARECIDA; SCARANO, WELLERSON RODRIGO. Defining suitable reference genes for RT-qPCR analysis on human sertoli cells after 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure. MOLECULAR BIOLOGY REPORTS, v. 41, n. 11, p. 7063-7066, . (11/04202-1, 12/00253-3)
DE FREITAS, ANDRE TEVES A. G.; PINHO, CRISTIANE FIGUEIREDO; AQUINO, ARIANA MUSA; DOMENICONI, RAQUEL FANTIN; JUSTULIN, LUIS ANTONIO; SCARANO, WELLERSON RODRIGO. Panax ginseng metabolite (GIM-1) modulates the effects of monobutyl phthalate (MBP) on the GPR30/GPER1 canonical pathway in human Sertoli cells. REPRODUCTIVE TOXICOLOGY, v. 96, p. 209-215, . (12/00253-3)
AQUINO GONCALVES DE FREITAS, ANDRE TEVES; RIBEIRO, MARIANA ANTUNES; PINHO, CRISTIANE FIGUEIREDO; PEIXOTO, ANDRE REBELO; DOMENICONI, RAQUEL FANTIN; SCARANO, WELLERSON R.. Regulatory and junctional proteins of the blood-testis barrier in human Sertoli cells are modified by monobutyl phthalate (MBP) and bisphenol A (BPA) exposure. TOXICOLOGY IN VITRO, v. 34, p. 1-7, . (12/00253-3)
DE FREITAS, ANDRE TEVES A. G.; PINHO, CRISTIANE FIGUEIREDO; DE AQUINO, ARIANA MUSA; FERNANDES, ANA ANGELICA H.; DOMENICONI, RAQUEL FANTIN; JUSTULIN, LUIS ANTONIO; SCARANO, WELLERSON RODRIGO. Panax ginseng methabolit (GIM-1) prevents oxidative stress and apoptosis in human Sertoli cells exposed to Monobutyl-phthalate (MBP). REPRODUCTIVE TOXICOLOGY, v. 86, p. 68-75, . (12/00253-3)

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