Epigenetic maturation of the oocyte and totipotence: the potential of the oocyte and its relationship with the ovarian follicular niche

• Grant number: 21/09886-8
• Support Opportunities: Research Projects - SPEC Program
• Duration: November 01, 2022 - October 31, 2027
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Lawrence Charles Smith
• Grantee: Lawrence Charles Smith
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Pesquisadores principais: Cláudia Lima Verde Leal
• Associated researchers: André Furugen Cesar de Andrade ; Carlos Eduardo Ambrósio ; Cibele Maria Prado Zinni ; Elisangela Chicaroni de Mattos ; Fabiana Fernandes Bressan ; Felipe Perecin ; Gisele Zoccal Mingoti ; Guilherme Pugliesi ; José Bento Sterman Ferraz ; Juliana Germano Ferst ; Juliano Coelho da Silveira ; Juliano Rodrigues Sangalli ; Laís Vicari de Figueiredo Pessôa ; Luciano Andrade Silva ; Maíra Bianchi Rodrigues Alves ; Marcella Pecora Milazzotto ; Marcelo Demarchi Goissis ; Naira Caroline Godoy Pieri ; Ricardo Perecin Nociti ; Tiago Henrique Camara de Bem
• Associated grant(s): 23/01579-4 - Manipulation of the in vitro environment aiming at the acquisition of totipotency in vitro by means of bovine induced pluripotent stem cells, AP.R; 23/04558-8 - Multi-user equipment granted from process 2021/09886-8: server and workstations, AP.EMU; 22/15066-6 - Multi-user equipment granted from process 2021/09886-8: Mica Confocal Microscope - Leica, AP.EMU
• Associated scholarship(s): 24/03347-6 - Analysis and acquisition of confocal microscopy images to evaluate the effects of meiotic blockage on oocyte epigenetic maturation and intrafollicular communication, BP.TT; 24/03373-7 - Technical training in next generation sequencing to study oocyte totipotency, BP.TT; 23/08037-2 - The potential of the oocyte and its relationship with the ovarian follicular niche, BP.PD; 22/15264-2 - Impact of MFN2 deficiency and maternal obesity on the oocyte and the transmission of metabolic syndromes, BP.DR; 21/14019-1 - Role of mitochondria-endoplasmic reticulum interaction on maternal inheritance of cardiac dysfunction, BP.PD

Abstract

The epigenetic mechanisms governing the ability of the female gamete, i.e. the oocyte, to become totipotent are at the center of many unanswered questions in biology and a better understanding of such a basic phenomenon offers a unique opportunity to develop novel biotechnologies with wide-reaching benefits for humans and animals. This thematic project brings together renowned Canadian and Brazilian experts working in a wide range of scientific fields from the subcellular to the whole organismal levels, who together aim to tackle the yet unanswered question in biology, i.e. what are the epigenetic cues provided by the follicular environment that enable the production of an oocyte capable of deriving all cells in an organism, including its perpetuation through the production of gametes for the next generation? Through the use of sophisticated retrospective approaches with state-of-the-art bioinformatic tools to analyze the epigenetic components at the molecular and cellular levels, a series of unique experimental models are aimed to (1) identify key molecular constituents involved in the oocyte-follicle interactions, (2) intervene on the meiotic resumption in vitro to simulate in vivo folliculogenesis, and (3) examine alternative models to unveil essential mechanisms of totipotency. The sharing of complementary know-how among the Canadian and Brazilian teams provides a distinctive opportunity to shed further light on fundamental mechanisms controlling the acquisition of totipotency by the oocyte. As practical relevance, humans and animals will benefit directly through the improvement and advent of novel assisted reproductive biotechniques that improve procreation in infertile couples, accelerate the dissemination of superior genotypes in domestic species, and restore threatened wildlife. (AU)