Role of Lipid Metabolism and Signaling in Mammalian Oocyte Maturation, Quality, and Acquisition of Competence

Abstract

It has been found that the quality of oocytes from obese women has been compromised and subsequent embryos displayed arrested development. The compromised quality may be either due to the poor or rich metabolic conditions such as imbalance or excession of lipids during oocyte development. Generally, lipids are mainly stored in the form of lipid droplets and are an important source of energy metabolism. Similarly, lipids are also essential signaling molecules involved in various biological cascades of oocyte maturation, growth and oocyte competence acquisition. To understand the role of lipids in controlling the oocyte development, we have comprehensively and concisely reviewed the literature and described the role of lipid metabolism in oocyte quality and maturation. Moreover, we have also presented a simplified model of fatty acid metabolism along with its implication on determining the oocyte quality and cryopreservation for fertilization.

Keywords: fertilization; lipid metabolism; obesity; oocyte development; oocyte maturation.

FIGURE 1

Proposed model of free fatty acid (FFA) mobilization and catabolism in COC. (A) Free fatty acids or non-esterified fatty acids (NEFAs) are incorporated with serum albumin and are transported to follicular fluids by fatty acid carrier or directly diffused through lipid bilayer. (B) The mobilization of triacylglycerol from lipoproteins in follicular fluids occurs due to enzymatic action of lipoprotein lipases through which free fatty acids are generated and become available for cellular uptake. (C) Intracellular triacylglycerols are stored in the cumulus cells and oocytes in the form of lipid droplets. These lipid droplets are activated and further liberate free fatty acids by lipase mediated hydrolysis. (D) All the liberated free fatty acids either intracellularly from lipid droplets or through transporter molecules from follicular fluids, are metabolized in the mitochondria and ATP is generated through β-oxidation.

FIGURE 2

Lipid signaling pathways during oocyte maturation. The flow chart representative diagram explaining the various signaling events occurs during mammalian oocyte maturation. Briefly, luteinizing hormone (LH) through its receptor luteinizing hormone receptor (LHR) stimulates the entry of arachidonic acid in theca cells (TCs) in the form of high density lipoprotein (HDL). Then HSL is activated through cAMP/PKA pathways, and initiates the release of cholesterol from lipid droplets. In the mitochondria, cholesterol molecules are converted into pregnenolone by action of steroidogenic acute regulatory protein (StAR). Furthermore, COX pathway is triggered inside the granulosa cells (GCs) via FSH stimulation which initiates the expression of aromatase and converts testosterone (T) into estradiol (E2). Estradiol further stimulates various pathways in the oocytes which safeguard the degradation of cAMP and concurrent inhibition of maturation-promoting factor (MPF). On the other hand, activation of progesterone (P4) signaling causes inhibition of cAMP production by blocking adenylate cyclase (AC) activity which results in MPF activation and GVBD.

FIGURE 3

Flow chart diagram describing the effect of obesity and advanced maternal age on oocyte maturation. Obesity and advanced maternal age cause improper lipid metabolism in oocyte which further affect spindle formation, lead to aneuploidy and poor embryonic development.

FIGURE 4

Pathophysiology of polycystic ovary syndrome (PCOS). The representative illustration of complex interactions underlying the pathophysiology of PCOS. Generally, insulin resistance occurs in PCOS that further causes hyperinsulinemia which is responsible for the majority of changes in PCOS women. Skeletal muscles and adipose tissues become insulin resistance with reduced glucose uptake and higher lipolysis, while the ovaries remain insulin sensitive. However, hyperinsulinemia occurs as a compensatory response to insulin resistance and stimulates enhanced production of androgens from ovaries and adrenal glands in PCOS women. In short, excess insulin stimulates increased androgen production in ovarian theca cells in response to luteinizing hormone, resulting in follicular arrest and anovulation. On the other hand, hyperinsulinemia causes suppression of hepatic sex hormone-binding globulin (SHBG) production and leads to hyperandrogenemia.