Epigenetic inheritance of predisposition to obesity: through the oocyte?
Maternal obesity is commonly associated with infertility; furthermore, strong evidence links between maternal obesity and offspring predisposition to obesity and associated comorbidities, such as cardiovascular disease. However, the extent to which this predisposition is a result of impairments to oocyte quality, as opposed to an altered intrauterine environment, is yet to be clearly elucidated. The ovaries of obese mothers present inflammation and dyslipidemia; therefore, the oocyte develops and matures in a physiologically altered environment, which could have consequences on oocyte quality including epigenetic information. The epigenome of the oocyte has the potential to control initial reprogramming events in the early embryo, as well as longer-term metabolic outcomes in the offspring. In this talk, I will present the results of a study investigating the impact of maternal obesity on the epigenomes of oocytes and developing embryos, including blastocyst and post-implantation stages, from C57BL/6J mice fed chow diet or high-fat diet for 16 weeks. I will try to answer two outstanding questions: i) the extent to which the oocyte epigenome senses metabolic changes in the mother; and ii) whether epigenetic changes established in the oocyte persist through the global wave of epigenetic reprogramming that occurs in early embryos.
António Galvão is an Assistant Professor at the Institute of Animal Reproduction and Food Research in Olsztyn, PAS, Poland and a Senior Research Scientist at the Babraham Institute in Cambridge, United Kingdom. He received his degree in veterinary medicine from Faculty of Veterinary Medicine, Lisbon, Portugal, and the PhD from University of Lisbon, Portugal. Throughout his PhD and first postdoc, António studied the immune-endocrine crosstalk controlling ovarian and endometrial function in the large animals. He was subsequently awarded a Fellowship for Excellence in Science, from the Polish Ministry of Higher Education, and appointed assistant professor at the IARFR and started instigating the impact of maternal obesity on the pathophysiology of ovarian failure. This work led to the award of a Marie Curie Individual Fellowship to train in cutting-edge single cell multiomic techniques to study epigenomics in the laboratory of Dr Gavin Kelsey, Babraham Institute in Cambridge, UK.
Within his research programme António integrates molecular, cellular and bioinformatic tools to study the cross-disciplinary link between maternal obesity, infertility, developmental programming and offspring predisposition to disease. He is interested in deciphering the impact of maternal obesity on ovarian and endometrial functional dysregulation. By applying state-of-the-art methods in single cell analysis and high throughput sequencing, he is seeking to elucidate the contribution of an obesogenic oocyte legacy, in contrast to that of the intrauterine environment, for developmental programming and intergenerational predisposition to obesity.