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Morphological and molecular aspects of the adrenal in rats exposed to a phthalate mixture during gland organogenesis/aging

Grant number: 21/10776-2
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2022
Effective date (End): January 31, 2023
Field of knowledge:Biological Sciences - Morphology - Embryology
Principal Investigator:Wellerson Rodrigo Scarano
Grantee:Natália Magosso
Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The adrenal glands are highly active and responsible for producing hormones that maintain homeostasis, control blood pressure and stress responses, and thus influence metabolism and growth. When these glands are early exposed to stressful factors, such as environmental toxins, they can trigger important responses that result in alterations in their development and functionality. Currently, the daily exposure of pregnant women to different endocrine disruptors (EDs) interfere with the individual's development, modifying the intrauterine microenvironment. Phthalates, ubiquitous in the environment, are a group of chemical compounds used as plasticizers to provide greater malleability and flexibility, and are considered DEs due to their antiandrogenic action. In this sense, understanding that constant exposure to phthalates is a current problem and can trigger important damage throughout life and in senescence, the aim of this study is to assess whether perinatal exposure to varying concentrations of the phthalate mixture, in proportions similar to those found in pregnant women, it modifies the steroidogenesis of young and senescent rats, as well as accelerating the aging of the glands. For this, pregnant females (SD) will be divided into 4 groups and treated daily (orally) from gestational day (DG) 10 to postnatal day (DPN) 21 with corn oil (vehicle; Control: C) or with combined phthalates, in three doses (20 ¼g/kg/d: T1; 200 ¼g/kg/d: T2; 200 mg/kg/d: T3) in the following proportion: 21% DEHP, 35% DEP, 15% DBP , 8% DiBP, 5% BBzP and 15% DiNP. In DPN 22 (young prepubescent), DPN 120 (young adults) and animals from the most effective treatment groups (T1 and T3) will be kept in vivarium until DPN540 (senescent). At the end of the respective periods, the animals will be weighed and euthanized. The right adrenal glands will be collected and fixed, histological sections (5µm) will be produced for morphological analysis using hematoxylin and eosin staining, and immunohistochemistry. The left adrenals will be frozen at -80°C in a biofreezer for analysis of gene expression of receptors and proteins that regulate steroidogenesis, in addition to the analysis of molecular markers involved in the aging process of the gland. (AU)

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