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Gestational exposure to betamethasone in rats: pharmacological reactivity of the isolated maternal uterine horn and initial development of the offspring testis

Grant number: 17/02764-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2017
Effective date (End): December 31, 2017
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Wilma de Grava Kempinas
Grantee:Jorge Willian Franco de Barros
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Corticotherapy has been widely used in obstetric practice in pregnant women at risk of preterm birth, promoting fetal lung maturation, consequently, decreasing the incidence of respiratory distress syndrome, mortality and neonatal morbidity. Studies conducted in our Laboratory have demonstrated that prenatal exposure to betamethasone promoted changes in the histophysiological aspect of the gonads of the male offspring of rats, both at puberty and adult life. In addition, administration of betamethasone increased post-implantation losses in directly exposed progenitors. Thus, the objective of the present work will be to perform an investigation of the mechanisms involved with these outcomes. The study will be conducted in two stages. Experiment 1: pregnant females on gestational day 19 will have their uterine horns removed and submitted to in vitro pharmacological reactivity assays in the presence of increasing concentrations of betamethasone, with the registration of the respective areas of tension developed. For Experiment 2, two experimental groups will be needed: Treated: pregnant females who will receive intramuscular treatment with 0.1 mg/kg betamethasone on gestational days 12, 13, 18 and 19; Control: females treated with the vehicle. The following parameters will be investigated in the male offspring of these matrices: On postnatal day (PND) 1 the body weight and the anogenital distance will be recorded; on PND 7, 14 and 28, one pup of each litter will be euthanized and the gonads will be collected and fixed for further histomorphometric analysis, Sertoli cell count, Leydig cell volume and immunohistochemistry for androgen receptors (AR) and Mullerian inhibiting substance (MIS). The project's theme is current and of great relevance, considering the use of this drug in the human clinic and due to the known action of glucocorticoids on fetal programming. Therefore, it is an experimental study with translational applications. In addition to generating new knowledge, it is intended to prepare qualified human resources in research and contribute to the progress of the country from the scientific and socio-economic point of view. (AU)

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)
FRANCO DE BARROS, JORGE WILLIAN; BORGES, CIBELE DOS SANTOS; MISSASSI, GABRIELA; PACHECO, TAINA LOUISE; KEMPINAS, WILMA DE GRAVA. Impact of intrauterine exposure to betamethasone on the testes and epididymides of prepubertal rats. Chemico-Biological Interactions, v. 291, p. 202-211, AUG 1 2018. Web of Science Citations: 1.

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