The role of fatty acids in oocyte and early embryo development Paul J. McKeegan A and Roger G. Sturmey A,B A Centre for Cardiovascular and Metabolic Research, Hull York Medical School, University of Hull, Hull, HU6 7RX, UK. B Corresponding author. Email: roger.sturmey@hyms.ac.uk Abstract. Growing evidence suggests that endogenous and exogenous fatty acids play diverse roles in developing mammalian oocytes and early embryos. In this review, we describe some of the regulatory roles of fatty acids in early development, in addition to their metabolic functions. We focus initially on the provision of individual fatty acids, and then discuss how these might affect metabolism, oxidative stress, membrane composition, cell signalling events and gene expression. We propose that ongoing research should focus on physiologically relevant ratios and combinations of fatty acids, rather than isolated individual fatty acids, as their combined roles are both subtle and complex. Changing the ratio of specific fatty acids in the diet of animal models, and in vitro culture medium can cause significant dysregulation of cellular processes and development, an issue that extends to human fertility. Introduction The study of metabolic activity of early embryos has tradition- ally focussed on the depletion and appearance of individual metabolites from the culture environment (Gardner and Leese 1986; Leese et al. 1986). From the early reports of Ralph Brinster, researchers have sought to discover how the early embryo modifies its environment in vitro, in the hope that improved understanding of individual embryo metabolism might yield biomarkers of viability to be used to select embryos for transfer in clinical IVF (Brinster 1968a, 1968b, 1969, 1971). This approach has been a modest success, with evidence to suggest that the pattern of consumption of any one of glucose (Rieger et al. 2002; Gardner et al. 2011), oxygen (Houghton et al. 1996; Thompson et al. 1996; Shiku et al. 2001; Scott et al. 2008; Lopes et al. 2010), pyruvate (Conaghan et al. 1993), amino acids (Brison et al. 2004), the appearance of lactate (Conaghan et al. 1993), or a combined measure of metabolism, known as metabolomics (Seli et al. 2008), might be predictive of a ‘healthy embryo’ in a variety of species. As well as generating possible markers of viability, data such as these have been fundamental in defining our current understanding of embryo metabolism. However, in many of the studies on embryo metabolism, the role of fatty acids has been overlooked. Recently we have seen the emergence of a body of literature that is beginning to consider the roles of fatty acids in periconceptual events. In this review, we will consider some of the most recent studies on the key effects and roles of fatty acids in oocyte and embryo development drawing on data from a variety of species. We will initially consider the supply and origin of fatty acids in the oocyte and early embryo, before discussing some of the effects of fatty acids on early embryo development. We will then briefly review the metabolic role of fatty acids, and conclude by considering some of the non-metabolic actions of these compounds. The origin of fatty acids in the oocyte and early embryo Fatty acids are typically stored in the cell cytoplasm in the form of triacylglycerol (TG), uncharged esters of glycerol subse- quently arranged as neutral lipid droplets that are virtually anhydrous and thus a highly concentrated store of metabolic energy. Whilst the major site of lipid droplet storage in adult mammals is the adipocyte, a specialised cell that possesses a cytoplasm composed almost entirely of a single large globule of TG, it is of interest to note that the oocytes and embryos of mammalian species such as the porcine, bovine and ovine also contain very high quantities of lipid in the ooplasm. This en- dogenous content of lipid is so high that these oocytes appear dark when visualised under the light microscope (Coull et al. 1998; Ferguson and Leese 1999; McEvoy et al. 2000), espe- cially when produced in vitro (Barcelo ´-Fimbres and Seidel 2011). Cat oocytes are also high in lipid (Guraya 1965) and it has been claimed that fatty acid levels of oocytes can be increased by a carnivorous diet (Spindler et al. 2000). It has been suggested that, on the basis of oxygen consumption, there is sufficient lipid to support the metabolic requirements of bovine and porcine preimplantation development as a sole energy source (Sturmey et al. 2009b). However, this feature of high levels of endogenous fat is by no means universal; the oocytes and embryos of mice are pale, and contain a low level of endogenous lipid (Loewenstein and Cohen 1964), with human oocytes containing an intermediate level (Matorras et al. 1998). Investigation of the CSIRO PUBLISHING Reproduction, Fertility and Development, 2012, 24, 59–67 http://dx.doi.org/10.1071/RD11907 Journal compilation Ó IETS 2012 www.publish.csiro.au/journals/rfd