Impact of paternal exposure to benzo(a)pirene from juvenile to peripubetal period in rats: multigenerational and transgenerational effects on reproductive parameters

• Grant number: 19/03284-6
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2019
• End date: May 31, 2022
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Arielle Cristina Arena
• Grantee: Arielle Cristina Arena
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Deeh Defo Parick Brice ; Glaura Scantamburlo Alves Fernandes ; Rafael Henrique Nóbrega

Abstract

Exposure to Endocrine Disruptors (EDs) during critical windows of development can cause epigenetic alterations, which can appear immediately or long after exposure, even in subsequent generations. Benzo(a)pyrene (BaP) is a persistent organic pollutant, widely distributed in the environment. Studies have shown that BaP accumulates in vital and reproductive organs, including the testis; and may interfere with the steroidogenesis process through interaction with the StAR protein. Our laboratory has demonstrated that the BaP exposure provoked significant changes in spermatogenesis in male rats exposed from the juvenile period to peripuberty and that this compound can act as an ED, presenting a non- monotonic response patterns. However, additional data on the cellular and molecular causes of these changes and their persistence on a transgenerational scale are insufficient. The aim of this study is to evaluate the consequences of paternal exposure to BaP, from the juvenile period to peripuberty, on F1 (multigenerational) and F2 (transgenerational) generations in males, in addition to investigating the mechanisms by which BaP caused a reproductive change in a parental generation (F0). Wistar male rats (Postnatal day (PND) 23) will be distributed in two groups: a control group (corn oil + DMSO) and one group exposed to 0.1 µg/kg/day of BaP. The animals will be treated for 31 consecutive days, by the oral route. In the first step, the F0 generation will be evaluated on PND 120: stress oxidative analysis, gene expression, hormone levels, immunohistochemistry, sperm chromatin protamination and genomic sequencing of imprinting genes, TUNEL and comet assay. In the first step, the F0 generation will be evaluated on PND 120: stress oxidative analysis, gene expression, hormone levels, immunohistochemistry, sperm chromatin protamination and genomic sequencing of imprinting genes, TUNEL and comet assay. In a second step, the possible impacts provoked by parental exposure to BaP on F1 and F2 generation will be investigated, through the following evaluations: sexual development, reproductive parameters, TUNEL assay, comet assay, stress oxidative analysis, hormonal dosage, gene expression, immunohistochemistry, sperm chromatin protamination and genomic sequencing of imprinting genes. For the conduction of this project, there will be the participation of a doctoral student, a master's degree and under graduation students, as well as researchers from national and international universities. The results obtained in the present study could provide a better understanding of the preconception origins of diseases through the paternal genome, which is necessary for the field of transgenerational epigenetics and, ultimately, will help to guide public health policies in the future. (AU)

Scientific publications

(5)

(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)

JORGE, BARBARA CAMPOS; CASALI REIS, ANA CAROLINA; STERDE, ERIKA TISSIANA; BALIN, PAOLA DA SILVA; SCARANO, WELLERSON RODRIGO; HISANO, HAMILTON; ARENA, ARIELLE CRISTINA. Exposure to benzo(a)pyrene from juvenile period to peripubertal impairs male reproductive parameters in adult rats. Chemosphere, v. 263, JAN 2021. (17/22176-4, 19/03284-6)

REIS, ANA CAROLINA CASALI; JORGE, BARBARA CAMPOS; PASCHOALINI, BEATRIZ RIZZO; BUENO, JESSICA NOGUEIRA; STEIN, JULIA; MOREIRA, SUYANE DA SILVA; MANOEL, BEATRIZ DE MANOEL; FERNANDES, GLAURA SCANTAMBURLO ALVES; HISANO, HAMILTON; ARENA, ARIELLE CRISTINA. Long-term reproductive effects of benzo(a)pyrene at environmentally relevant dose on juvenile female rats. DRUG AND CHEMICAL TOXICOLOGY, v. N/A, p. 9-pg., 2022-07-29. (17/22176-4, 19/03284-6)

JORGE, BARBARA CAMPOS; STEIN, JULIA; REIS, ANA CAROLINA CASALI; BUENO, JESSICA NOGUEIRA; PASCHOALINI, BEATRIZ RIZZO; MOREIRA, SUYANE DA SILVA; MANOEL, BEATRIZ DE MATOS; ARENA, ARIELLE CRISTINA. Paternal low-dose benzo(a)pyrene exposure in rats impairs sexual development and fertility of the paternal lineage in F2 generation: A transgenerational study. Toxicology, v. 494, p. 10-pg., 2023-08-01. (19/03284-6, 19/03264-5, 19/07024-9)

JORGE, BARBARA CAMPOS; CASALI REIS, ANA CAROLINA; STEIN, JULIA; BALIN, PAOLA DA SILVA; STERDE, ERIKA TISSIANA; BARBOSA, MARIANA GAZOLI; DE AQUINO, ARIANA MUSA; LEITE KASSUYA, CANDIDA APARECIDA; ARENA, ARIELLE CRISTINA. Parental exposure to benzo(a)pyrene in the peripubertal period impacts reproductive aspects of the F1 generation in rats. REPRODUCTIVE TOXICOLOGY, v. 100, p. 126-136, MAR 2021. (17/22176-4, 19/03284-6)

JORGE, BARBARA CAMPOS; STEIN, JULIA; REIS, ANA CAROLINA CASALI; DE MATOS MANOEL, BEATRIZ; NAGAOKA, LIVIA TRIPPE; ARENA, ARIELLE CRISTINA. Insights from the maternal lineage of the F2 generation after exposure to an environmentally relevant dose of benzo(a)pyrene in the male rats of F0 generation. Environmental Science and Pollution Research, v. N/A, p. 14-pg., 2023-10-03. (19/03284-6, 19/03264-5)