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Immediate and transgenerational epigenetic effects of heat stress on female gametes

Grant number: 17/20125-3
Support type:Research Program on Global Climate Change - Regular Grants
Duration: August 01, 2018 - July 31, 2020
Field of knowledge:Agronomical Sciences - Veterinary Medicine
Principal Investigator:Fabíola Freitas de Paula Lopes
Grantee:Fabíola Freitas de Paula Lopes
Home Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

Summer heat stress depression in fertility is a multifactorial problem. It has been shown that elevated temperature compromise follicular dynamics, hormonal secretion, uterine blood flow and endometrial function. Moreover, there is a great amount of evidence indicating that the oocyte and the early embryo are very susceptible to elevated temperature. Such reduction in fertility has been worsened by global warming. Therefore, a better understanding of the mechanisms underlying the impact of heat stress on oocyte function is necessary to the development of strategies to mitigate the deleterious effects of heat stress on fertility and consequent seasonality in milk production. Immediate and delayed effects of heat stress on oocyte function have been well characterized. The follicle-enclosed growing oocyte is very susceptible to heat stress. There is evidence that heat stress affects the series of cellular and molecular events triggered during oocyte growth compromising oocyte maturation, fertilization and preimplantation embryonic development. DNA methylation reprogramming is a major event that takes place during oocyte growth and early embryo development. Changes in the epigenome may be induced by environmental exposures, however, little is known regarding the effects of environmental stress during oogenesis on the epigenome of gametes and subsequent embryos. Moreover, recent evidence suggests that epigenetic variation may be transmitted from parents to offspring through their gametes, and that epigenetic modifications are not always completely erased between generations. The main goal of this study is to determine the effect of elevated temperature during oocyte growth on DNA methylation reprogramming during gametogenesis and preimplantation embryonic development and assess whether heat stress-induced epigenetic modifications are transgenerationally transmitted. The study will employ in vivo approaches using two animal models (mouse and bovine) to evaluate immediate and transgenerational effects of heat stress exposure on DNA methylation and gene regulation. In the first series of studies a mouse model will be established to investigate the effect of in vivo heat stress during oocyte growth on DNA methylation. A genome-wide analysis followed by single locus validations will be performed to identify immediate and transgenerational effects. In the second series of studies, variations in DNA methylation identified in the mouse will be investigated on the bovine species in vivo. A seasonal heat stress model with Holstein cows will be applied to determine the DNA methylation modifications in the bovine oocyte. (AU)