A role of lipid metabolism during cumulus-oocyte complex maturation: impact of lipid modulators to improve embryo production

Abstract

Oocyte intracellular lipids are mainly stored in lipid droplets (LD) providing energy for proper growth and development. Lipids are also important signalling molecules involved in the regulatory mechanisms of maturation and hence in oocyte competence acquisition. Recent studies show that LD are highly dynamic organelles. They change their shape, volume, and location within the ooplasm as well as their interaction with other organelles during the maturation process. The droplets high lipid content has been correlated with impaired oocyte developmental competence and low cryosurvival. Yet the underlying mechanisms are not fully understood. In particular, the lipid-rich pig oocyte might be an excellent model to understand the role of lipids and fatty acid metabolism during the mammalian oocyte maturation and their implications on subsequent monospermic fertilization and preimplantation embryo development. The possibility of using chemical molecules to modulate the lipid content of oocytes and embryos to improve cryopreservation as well as its biological effects during development is here described. Furthermore, these principles of lipid content modulation may be applied not only to germ cells and embryo cryopreservation in livestock production but also to biomedical fundamental research.

Figure 1

Morphological appearance of immature pig oocytes.

Figure 2

A model for lipid droplets (LD) biogenesis ((a), (b)) during pig oocyte (c) maturation: (a), de novo synthesis of LD in endoplasmic reticulum membrane and (b) LD coalescence process, with lipid trafficking mediated by snare (Snare P, orange batons) and caveolins (orange coiled lines) proteins (based on a study by Suzuki et al. [18]). Perilipins proteins (TIP47 green batons) involved in the mechanism of lipolysis regulation. (c) Pig oocyte with 24 hours of in vitro maturation. Scale bar 50 μm. CE, cholesterol esters; ER, endoplasmic reticulum; TGA, triacylglycerols.

Figure 3

Immature pig oocyte with lipid droplets (LD) highlighted in white colour (LD areas were measured using Image J software) and scale bar 50 μm.

Figure 4

Hypothetical model for the effects of forskolin and trans-10, cis-12 conjugated linoleic acid (CLA) in the regulation of oocyte lipid metabolism and developmental competence acquisition: red colour and solid arrows, stimulation of cAMP intracellular levels, PKA and MAPK pathways by forskolin (see text for details); potential mechanisms of CLA action are also in red but illustrated by dashed arrows, including stimulation of PKA and MAPK pathways interfering with LD lipolysis, control of oocyte gene expression, and protein synthesis, namely, perilipins. Left, the cytoplasmic membrane and different events that are crucial for suitable oocyte maturation are represented in blue. R and G are the transmembrane G-protein-coupled receptor activated by different hormones or EGF (blue triangle) during this process. Red arrows illustrate the activity of different intracellular messengers and fatty acids regulating oocyte lipid metabolism and quality. DAG, diacylglycerol, DdGA, diradilglyceride, PIP2, phosphatidylinositol 4,5 bisphosphate, IP3, inositol 1,4,5-trisphosphate; PKA, protein kinase A; PKC, protein kinase C, MAPK, mitogen protein kinase; AC, adenylyl cyclase; HSL, hormone sensitive lipase; MGL, monoglyceride lipase; P, perilipin protein; LD, lipid droplet; NEFA, nonesterified fatty acids.