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Reproductive development of male rats exposed to the hypolipemic agent rosuvastatin.

Grant number: 11/15065-5
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): March 01, 2012
Effective date (End): February 28, 2014
Field of knowledge:Biological Sciences - Morphology - Embryology
Principal Investigator:Wilma de Grava Kempinas
Grantee:Gabriel Adan Araújo Leite
Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil


Dyslipidemy is a frequent disorder that have been manifested early in the population as a consequence of the increase of the number of obeses. Statins are inhibitors of the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA redutase) and are, therefore, responsible for reducing total cholesterol, mainly LDL-cholesterol. Rosuvastatin is a last generation statin and it presents several pharmacological advantages and superior inhibitory effects compared to other statins. Considering the use of hypolipemic substances by children and the lack of studies on the possible reproductive effects, we propose the present experimental study in that young rats will be exposed to rosuvastatin from weaning until puberty installation, evaluating immediate and late (sexual maturity) reproductive parameters. The choice of the exposure "window" is an attempt to mimic the human situation in that some children need the drug during the childhood and adolescence. For this, recently-weaned rats will be divided into three experimental groups and will receive 0, 3 and 10 mg/Kg/day of rosuvastatin, from post-natal day 21 until puberty installation, when part of the animals will be sacrificed and will be evaluated as to hormonal levels and histological aspect of the gonads and epididymis. The other rats will be maintained until sexual maturity, when they will be evaluated for sexual behavior, hormonal levels, sperm production, reserves and quality and fertile potential, besides testis and epididymis histology and immunohistochemistry for androgen receptors. Expected results are the preparation of qualified human resources in Biology and Toxicology of Reproduction and the achievement of new knowledge on the adverse effects of statins on the male reproductive tract, publishing the results in international journals, as well as presenting communications in scientific meetings.

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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)
ARAUJO LEITE, GABRIEL ADAN; SANABRIA, MARCIANA; CAVARIANI, MARILIA MARTINS; ANSELMO-FRANCI, JANETE APARECIDA; FELIPE PINHEIRO, PATRICIA FERNANDA; DOMENICONI, RAQUEL FANTIN; KEMPINAS, WILMA DE GRAVA. Lower sperm quality and testicular and epididymal structural impairment in adult rats exposed to rosuvastatin during prepuberty. JOURNAL OF APPLIED TOXICOLOGY, v. 38, n. 6, p. 914-929, . (11/15065-5)
ARAUJO LEITE, GABRIEL ADAN; ROSA, JOSIANE DE LIMA; SANABRIA, MARCIANA; CAVARIANI, MARILIA MARTINS; ANSELMO FRANCI, JANETE APARECIDA; FELIPE PINHEIRO, PATRICIA FERNANDA; KEMPINAS, WILMA DE GRAVA. Delayed reproductive development in pubertal male rats exposed to the hypolipemiant agent rosuvastatin since prepuberty. REPRODUCTIVE TOXICOLOGY, v. 44, p. 93-103, . (11/15065-5)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
LEITE, Gabriel Adan Araújo. Desenvolvimento reprodutivo de ratos machos expostos ao agente hipolipemiante rosuvastatina. 2014. Master's Dissertation - Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu Botucatu.

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