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Interference of in utero exposure to di-n-butyl phthalate and excessive consumption of saturated fat to reproductive parameters of gerbil

Grant number: 14/04146-2
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2014
Effective date (End): February 28, 2018
Field of knowledge:Biological Sciences - Morphology - Histology
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Rejane Maira Góes
Grantee:Ana Carolina Negrin
Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil


The deleterious effects of endocrine disrupting chemicals (EDC) and obesity on reproductive parameters represent serious problems of modern life and has attracted increasing scientific interest. Toxicological studies show that EDC such as phthalates, cause, at high doses, severe abnormalities in the male genital system and damage to sperm production. Obesity has also been linked to damage to male fertility because it compromises the quality and quantity of sperm. However, there is little information about the influence of these environmental factors when analyzed together. In recently completed study, we found that exposure to di-n-butyl phthalate (DBP) in association with excess of dietary fat, from pregnancy to adulthood, have additive effects, causing losses to the daily sperm production and synthesis of testosterone. In this research we aim to get more details on this issue by evaluating the consequences of exposure to high doses of DBP during pregnancy to the testis and the sperm parameters of adult gerbils, and to examine whether excess of dietary saturated fat interferes in these effects. So, are set two objectives: 1) examine the effects of exposure to the lowest DBP dose resulting in adverse effects (LOAEL - lowest-observed-adverse-effect level), during pregnancy, the structure and testicular function and sperm parameters of adult gerbils, and 2) examine the effects of excess dietary saturated fat from weaning up to adulthood on these parameters and their influence on changes caused by exposure to DBP. To this end, pregnant females are divided into three groups: 1) untreated, 2) treated with 0.1 ml of mineral oil, and 3) treated with 100 mg / kg / day DBP dissolved in 0.1 ml of mineral oil. The administration will be performed oral (gavage) from the 8th to the 23th day of gestation. Male offspring (n = 15/group; 1 animal / family) will be treated or not with diet rich in saturated fat from postnatal day 30 up to adulthood. The response of the adult testis will be examined by histological and stereological analysis and by histopathological changes. Will be determined following sperm parameters: daily sperm production, spermatic efficiency, sperm transit time through the epididymis and sperm motility. In order to clarify the possible mechanisms involved in the observed changes, we analyze the serum and testicular concentrations of testosterone and estrogen and intratesticular expression of its receptors (AR and ER). The expression of nuclear receptor activators of proliferation of peroxisomes ³ (PPAR ³) and liver X receptor type ± (LXR ±) will be investigated and mapped the major cell populations of the testis. The rate of apoptosis of testicular cells will be investigated. The lipid profile and blood glucose and insulin resistance are evaluated. We believe that understanding how these situations isolated and together affect the reproductive biology of this rodent will bring new information on the mechanisms involved in testicular response due to obesity and phthalate exposure in utero. (AU)

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Scientific publications
(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)
NEGRIN, ANA CAROLINA; DE JESUS, MARIANA MARCIELO; CHRISTANTE, CAROLINE MARIA; HUMBERTO DA SILVA, DANILO GRUNIG; TABOGA, SEBASTIAO ROBERTO; PINTO-FOCHI, MARIA ETELVINA; GOES, REJANE MAIRA. Maternal supplementation with corn oil associated or not with di-n-butyl phthalate increases circulating estradiol levels of gerbil offspring and impairs sperm reserve. REPRODUCTIVE TOXICOLOGY, v. 81, p. 168-179, . (13/16368-7, 14/04146-2)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
NEGRIN, Ana Carolina. Interference of in utero exposure to di-n-butyl phthalate and an excessive consumption of saturated-fat diet in the reproductive parameters of the gerbil. 2018. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.

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