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Steroidogenesis in the offspring of rats submitted to maternal protein restriction: evaluation and functional studies of microRNAs/mRNAs responsive to estrogen in the prostate

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Author(s):
Luiz Marcos Frediani Portela
Total Authors: 1
Document type: Master's Dissertation
Press: Botucatu. 2021-04-19.
Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
Defense date:
Advisor: Luis Antonio Justulin Júnior
Abstract

A maternal low protein diet (MLPD) is a determining factor in altering the health of offspring throughout life, placing it within the approach of the Developmental Origin of Health and Disease (DOHaD). It is associated with MLPD changes in serum levels of steroid hormones, loss of normal prostate development and becomes a determining factor for the increased incidence of prostate cancer (PCa) with aging. Here we describe that animals on a postnatal day (PND) 21 and that submitted MLPD, had low birth weight, decreased serum levels of progesterone, dehydroepiandrosterone, increased cholesterol, testosterone, and estrogen. We associate the increase in these hormones, especially estrogen, with the increased expression of Cyp19a1 (aromatase) in the skin, liver, and adrenal gland. As a result of this increase in estrogen levels, we observed a loss of normal development of the ventral prostatic (VP) lobe leading to smaller glands. Studies of miRNA sequencing showed the miR206-3p upregulated in the VP of these animals, through in silico analyzes we identified that the targets predicted to miR206-3p are potentially contributing to prostatic carcinogenesis, these targets lead to worse prognostic of survival in patients human with PCa. Assays that mimic the expression of miR206 in human prostatic cells normal (PNT2 lineage) showed a reduction in the cell viability as a result of an increase in miR206-3p. (AU)

FAPESP's process: 18/26120-6 - Steroidogenesis in the offspring of rats submitted to maternal protein restriction: Evaluation of estrogen-responsive microRNAs / mRNAs and functional prostate studies
Grantee:Luiz Marcos Frediani Portela
Support Opportunities: Scholarships in Brazil - Master