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Neuroendocrine and metabolic adjustments in the hypothalamic-pituitary-gonadal, interrenal and thyroid axes in Astyanax altiparanae females (Characiformes: Characidae) exposed to anti-inflammatory drugs

Grant number: 20/01527-6
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2020
Status:Discontinued
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal Investigator:Renata Guimarães Moreira Whitton
Grantee:Filipe Guilherme Andrade de Godoi
Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:14/16320-7 - Impacts of climate/environmental change on the fauna: an integrative approach, AP.PFPMCG.TEM
Associated scholarship(s):22/07911-8 - Assessment in the mode of action of emerging concern pharmaceuticals in Gammarus locusta (Crustacea: Amphipoda) using RNA-Seq approach with ecological parameters, BE.EP.DR

Abstract

Environmental contamination in the aquatic ecosystems by Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) has been observed mainly due to a persistence characteristic and wrong disposal of such compounds. These NSAIDs, eg. Diclofenac (DCF) and Ibuprofen (IBU) has caused several endocrine disorders in the Hypothalamus- Pituitary- Gonads (HPG) axis on the aquatic organisms acting as endocrine disrupting chemicals (EDCs). Studies in vivo using Astyanax altiparanae males showed the impacts of DCF in the reduction of 17²-estradiol e testosterone as well as morphological change on the hepatocytes. Also, reduction of gonadotropins related genes expression was observed in vitro studies using the males of same species, these data evidenced the impacts of NSAIDs as EDCs on different levels of HPG axis. As DCF, IBU has showed endocrine disorders in fish impacting the eggs production and modulating pituitary genes related to female reproduction. Also, both compounds affect other endocrine pathways including the Hypothalamus- Pituitary - Thyroid (HPT) axis and hypothalamus-pituitary -interrenal (HPI) axis where the cross-talk between these axes have an integrative importance in the modulation of reproduction. Considering the effects of NSAIDs in the fish neuroendocrine physiology and the crosstalk between the axes in reproduction, the present proposal has the main objective of evaluate the integrative responses in vivo of HPI and HPT axes and the impacts in the reproductive physiology adjustments in the A. altiparanae females expose acutely and chronically to DCF and IBU, as well as, the in vitro responses in the pituitary gland and ovaries. The study will use molecular, biochemistry and histological techniques in order to answer the proposed objectives related to the physiological adjustments in the axes of the females exposed to the NSAIDs. (AU)

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