Cadmium : Toxic effects on the reproductive system and the embryo

Minireview: Functions of the cumulus oophorus during oocyte maturation, ovulation, and fertilization.

The environment that the cumulus oocyte complex (COC) is exposed to during either in vivo or in vitro maturation (IVM) can have profound effects on the success of fertilisation and subsequent embryo development. Glucose is a pivotal metabolite for the COC and is metabolised by glycolysis, the pentose phosphate pathway (PPP), the hexosamine biosynthesis pathway (HBP) and the polyol pathway. Over the course of oocyte maturation, a large proportion of total glucose is metabolised via the glycolytic pathway to provide substrates such as pyruvate for energy production. Glucose is also the substrate for many cellular functions during oocyte maturation, including regulation of nuclear maturation and redox state via the PPP and for the synthesis of substrates of extracellular matrices (cumulus expansion) and O-linked glycosylation (cell signalling) via the HBP. However, the oocyte is susceptible to glucose concentration-dependent perturbations in nuclear and cytoplasmic maturation, leading to poor embryonic development post-fertilisation. For example, glucose concentrations either too high or too low result in precocious resumption of nuclear maturation. This review will discuss the relevant pathways of glucose metabolism by COCs during in vivo maturation and IVM, including the relative contribution of the somatic and gamete compartments of the COC to glucose metabolism. The consequences of exposing COCs to abnormal glucose concentrations will also be examined, either during IVM or by altered maternal environments, such as during hyperglycaemia induced by diabetes and obesity.

/pdf/the-pivotal-role-of-glucose-metabolism-in-determining-oocyte-3vgm0a4rmw.pdf

The pivotal role of glucose metabolism in determining oocyte developmental competence

There has been an improvement in the blastocyst rates achieved following in-vitro embryo production that can largely be attributed to improved embryo culture conditions based on an increased knowledge of the in-vivo environment, as well as the metabolic needs of the embryo. Despite this, in-vitro oocyte maturation (IVM) conditions have remained largely unchanged. Within the antral follicle, numerous events affect oocyte maturation and the acquisition of developmental competency, including: interactions between somatic cells of the follicle (in particular cumulus cells) and the oocyte; the composition of follicular fluid; and the temperature and vascularity of the follicular environment. Many of these factors change with follicle size and oocyte growth. In contrast, culture conditions for IVM are based on somatic cells that often do not reflect the follicular environment, and/or have complex compositions or additives such as macromolecule supplements that are undefined in nature. Metabolites included in media such as glucose, pyruvate, oxygen and amino acids have been shown to have differential influences on oocyte maturation and competency. Manipulation of these factors and application of gained knowledge of the in-vivo environment may result in improved in-vitro oocyte maturation and overall in-vitro embryo production.

/pdf/effects-of-in-vivo-and-in-vitro-environments-on-the-14ixyv9kff.pdf

Effects of in-vivo and in-vitro environments on the metabolism of the cumulus–oocyte complex and its influence on oocyte developmental capacity

TSG-6 expression is upregulated in many cell types in response to a variety of proinflammatory mediators and growth factors. This protein is detected in several inflammatory disease states (e.g. rheumatoid arthritis) and in the context of inflammation-like processes, such as ovulation, and is often associated with extracellular matrix remodelling. TSG-6 has anti-inflammatory and chondroprotective effects in various models of inflammation and arthritis, which suggest that it is a component of a negative feedback loop capable of downregulating the inflammatory response. Growing evidence also indicates that TSG-6 acts as a crucial factor in ovulation by influencing the expansion of the hyaluronan-rich cumulus extracellular matrix in the preovulatory follicle. TSG-6 is a member of the Link module superfamily and binds to hyaluronan (a vital component of extracellular matrix), as well as other glycosaminoglycans, via its Link module. In addition, TSG-6 forms both covalent and non-covalent complexes with inter-alpha-inhibitor (a serine protease inhibitor present at high levels in serum) and potentiates its anti-plasmin activity.

TSG-6: a multifunctional protein associated with inflammation.

The application of a quantitative videographic technique has provided an opportunity to compare the quantitative volumetric expansion of cultured oocyte complexes (COCs) to quantitative changes in gap junction down-regulation and hyaluronic acid synthesis and to investigate the effects of physiological agents that influence these processes. Results of these experiments support the idea that the down-regulation of cumulus gap junctions is required for the initial phase of cumulus cell disaggregation and confirm earlier reports that hyaluronic acid synthesis plays a major role in additional expansion of the cumulus. These studies also provide evidence that the degree of expansion observed in culture lacking substrates of hyaluronic synthesis is significantly attentuated when compared with expansion occurring in vivo and that the failure of cultured complexes to expand maximally can be overcome by the addition of substrates of hyaluronic acid synthesis to the culture medium.

Hyaluronic acid synthesis and gap junction endocytosis are necessary for normal expansion of the cumulus mass

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Hyaluronic acid synthesis and gap junction endocytosis are necessary for normal expansion of the cumulus mass