Effects of in utero exposure to betamethasone on puberty instalation and reproductive parameters of Female Wistar rats

• Grant number: 14/13660-1
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2014
• Effective date (End): September 30, 2016
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Wilma de Grava Kempinas
• Grantee: Tainá Louise Pacheco
• Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Glucocorticoids are powerful drugs with anti-rheumatic, anti-inflammatory and immunosuppressive action, and are the drugs used for antenatal therapy, promoting fetal lung maturation and thus reducing the incidence of neonatal respiratory distress syndrome, mortality and morbidity with featured glucocorticoid betamethasone. Studies conducted in partnership with our laboratory have shown that prenatal exposure to this drug promoted changes in testosterone levels and sperm parameters of male offspring, however there are few studies on female offspring. The objective of this study is to evaluate possible changes in installation of puberty and reproductive parameters, with emphasis on the fertility of female rats caused by in utero exposure to betamethasone. For this, pregnant rats will be allocated into a control group and treated with 0.1 mg / kg betamethasone on gestational days 12,13,18 and 19. The female pups of the first generation will be assessed in reference to litter weight at birth, the anogenital distance, nipples count, age of vaginal opening and first estrus (indicators of puberty onset), weight and histology of ovaries at 75 days of age, weight of liver, kidney, pituitary and adrenal hormone measurements, estrous cycle regularity, sexual behavior and fertility after natural mating. The present investigation is timely and very relevant, considering the wide use of this drug therapies with maternal risk of premature birth and due to the known action of glucocorticoids on fetal programming. In addition to generating new knowledgment on the effects of prenatal exposure to betamethasone, we intend to prepare qualified human resources in reproductive toxicology.

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)

ACEVEDO-RODRIGUEZ, A.; KAUFFMAN, A. S.; CHERRINGTON, B. D.; BORGES, C. S.; ROEPKE, T. A.; LACONI, M. Emerging insights into hypothalamic-pituitary-gonadal axis regulation and interaction with stress signalling. Journal of Neuroendocrinology, v. 30, n. 10, SI OCT 2018. Web of Science Citations: 7.

ADRIANA ABRUZZESE, GISELLE; CRISOSTO, NICOLAS; KEMPINAS, WILMA DE GRAVA; SOTOMAYOR-ZARATE, RAMON. Developmental programming of the female neuroendocrine system by steroids. Journal of Neuroendocrinology, v. 30, n. 10, SI OCT 2018. Web of Science Citations: 2.

BORGES, CIBELE S.; PACHECO, TAINA L.; GUERRA, MARINA T.; BARROS, ALINE L.; SILVA, PATRICIA V.; MISSASSI, GABRIELA; DA SILVA, KATIUSSIA PINHO; ANSELMO-FRANCI, JANETE A.; PUPO, ANDRE S.; KEMPINAS, WILMA DE G. Reproductive disorders in female rats after prenatal exposure to betamethasone. JOURNAL OF APPLIED TOXICOLOGY, v. 37, n. 9, p. 1065-1072, SEP 2017. Web of Science Citations: 6.