Metabolism throughout follicle and oocyte development in mammals

Abstract

Metabolic studies of mammalian embryos started with the development of in vitro culture systems more than 40 years ago. More recently, metabolic studies have begun to shed light on the requirements of growing oocytes/follicles from the earliest stages of folliculogenesis. While growing oocytes preferentially metabolise pyruvate over glucose, the somatic compartment of ovarian follicles is more glycolytic. The metabolic preferences of the oocyte are reflected in the early zygote, which becomes increasingly dependent on glycolytic energy production as development progresses to the blastocyst stage. Furthermore, the intricate metabolic relationship between each oocyte and its somatic surroundings is critical for oocyte growth and developmental competence. Measurements of amino acid turnover in bovine oocytes indicate that glutamine, arginine and leucine are consistently depleted, while alanine is produced, showing similarities with amino acid turnover in preimplantation embryos. Amino acid profiling is a good predictor of embryo quality and might also turn out to be a predictor of oocyte developmental competence. Finally, recent studies have uncovered lipid metabolism in oocytes and early embryos, suggesting that endogenous fatty acids might be used for energy production. Together, metabolic studies have revealed the multiplicity of energetic substrates used by oocytes and early embryos, and suggest that the versatility of the metabolic pathways available for energy production is key for high developmental potential. Metabolic studies of early embryos are now being applied to follicle culture, and the goal of describing the metabolome of the growing oocyte in its follicle is now very attainable.

Hypoxia-mediated carbohydrate metabolism and transport promote early-stage murine follicle growth and survival

“…Glucose metabolism via glycolysis and the pentose phosphate pathway is essential for production of energy substrates, NADPH, ribose-5-phosphate, and purine precursors (8,35). Glycolysis produces lactate and pyruvate, which is an essential energy substrate for oocytes and is transported via specialized transporters from granulosa cells to oocytes (28,33).…”

“…LOW OXYGEN TENSION PROMOTES FOLLICLE SURVIVAL produce lactate and consume twofold more pyruvate than glucose, suggesting that both glycolysis and TCA oxidation occur at this stage (8,13). Pyruvate is the preferred substrate for energy metabolism in primordial follicles and is attributed to consumption by the oocyte (4, 10, 13), whereas the low levels of glucose consumption and lactate production are attributed to glycolysis by granulosa cells (13).…”

“…Oxygen consumption by murine oocytes is stage dependent and closely linked to carbohydrate metabolism and energy demand at different stages (8,13). Follicles in this study were cultured using a static culture model (no media refresh) compared with a conventional culture model (media refresh).…”

“…By design, ovarian follicles operate in a moderate hypoxic environment rather than an anoxic one (16). Granulosa cells use relatively less O 2 and convert glucose to pyruvate and lactate via the glycolytic pathway; the pyruvate is shunted to oocyte, which uses it and O 2 to create ATP via the TCA cycle (8,13).…”

The effect of nutrition and metabolic status on the development of follicles, oocytes and embryos in ruminants

“…Within the follicle, glucose can be metabolized by four different pathways: (i) by glycolysis to produce ATP and pyruvate or lactate; (ii) by the pentose phosphate pathway to provide precursors for the synthesis of purine nucleotides and NADPH for various biosynthetic pathways including antioxidant defence; (iii) by the hexosamine biosynthetic pathway to provide substrates for the glycosylation of proteins and the synthesis of the hyaluronic acid required for cumulus expansion; and (iv) by the polyol pathway producing sorbitol and fructose whose roles in follicular function remains largely unknown (for a review see Collado-Fernandez et al (2012)). In cattle, the role of these four pathways for the utilization of glucose during the growth and development of follicles and Nutrients and metabolic hormones and ruminant ovary their oocytes is not clearly known.…”