Significance: Four decades have passed since the first successful human embryo conceived from a fertilization in vitro. Despite all advances, success rates in assisted reproduction techniques still remain unsatisfactory and it is well established that oxidative stress can be one of the major factors causing failure in in vitro fertilization (IVF) techniques. Recent Advances: In the past years, researchers have been shown details of the supportive role CCs play along oocyte maturation, development, and fertilization processes. Regarding redox metabolism, it is now evident that the synergism between gamete and somatic CCs is fundamental to further support a healthy embryo, since the oocyte lacks several defense mechanisms that are provided by the CCs. Critical Issues: There are many sources of reactive oxygen species (ROS) in the female reproductive tract in vivo that can be exacerbated (or aggravated) by pathological features. While an imbalance between ROS and antioxidants can result in oxidative damage, physiological levels of ROS are essential for oocyte maturation, ovulation, and early embryonic growth where they act as signaling molecules. At the event of an assisted reproduction procedure, the cumulus/oophorus complex is exposed to additional sources of oxidative stress in vitro. The cumulus cells (CCs) play essential roles in protecting the oocytes from oxidative damage. Future Directions: More studies are needed to elucidate redox biology in human CCs and oocyte. Also, randomized controlled trials will identify possible benefits of in vivo or in vitro administration of antioxidants for patients seeking IVF procedure. Antioxid. Redox Signal. 32, 522-535.
In vitro maturation (IVM) is an assisted reproduction technique with reduced hormone-related side effects. Several attempts to implement IVM in routine practice have failed, primarily due to its relatively low efficiency compared to conventional in vitro fertilization (IVF). Recently, capacitation (CAPA)-IVM, a novel two-step IVM method, has improved the embryology outcomes through synchronizing the oocyte nuclear and cytoplasmic maturation. However, the efficiency gap between CAPA-IVM and conventional IVF is still noticeable especially in the numerical production of good quality embryos. Considering the importance of glucose for oocyte competence, its metabolization is studied within both in vivo and CAPA-IVM matured mouse cumulus-oocyte-complexes (COCs) through direct measurements in both cellular compartments, from transcriptional and translational perspectives, to reveal metabolic shortcomings within the CAPA-IVM COCs. These results confirmed that within in vivo COC, cumulus cells are highly glycolytic, whereas oocytes, with low glycolytic activity, are deviating their glucose towards pentose phosphate pathway. No significant differences were observed in the CAPA-IVM oocytes compared to their in vivo counterparts. However, their cumulus cells exhibited a precocious increase of glycolytic activity during the pre-maturation culture step and activity was decreased during the IVM step. Here, specific alterations in mouse COC glucose metabolism due to CAPA-IVM culture were characterized using direct measurements for the first time. Present data show that, while CAPA-IVM cumulus cells are able to utilize glucose, their ability to support oocytes during final maturation is impaired. Future CAPA-IVM optimization strategies could focus on adjusting culture media energy substrate concentrations and/or implementing co-culture strategies.
Establishing an ideal human follicle culture system for oncofertility patients relies mainly on animal models since donor tissue is scarce and often of suboptimal quality. The in vitro system developed in our laboratory supports the growth of prepubertal mouse secondary follicles up to mature oocytes. Given the importance of glucose in preparing the oocyte for proper maturation, a baseline characterization of follicle metabolism both in the culture system and in vivo was carried out. Markers of glucose-related pathways (glycolysis, tricarboxylic acid (TCA) cycle, pentose phosphate pathway (PPP), polyol pathway, hexosamine biosynthesis pathway (HBP)) as well as for the antioxidant capacity were measured in the different follicle cell types by both enzymatic activities (spectrophotometric detection) and gene expression (qPCR). This study confirmed that in vivo the somatic cells, mainly granulosa, exhibit intense glycolytic activity, while oocytes perform PPP. Throughout the final maturation step, oocytes in vivo and in vitro showed steady levels for all the key enzymes and metabolites. On the other hand, ovulation triggers a boost of pyruvate and lactate uptake in cumulus cells in vivo, consumes reduced nicotinamide adenine dinucleotide phosphate (NADPH) and increases TCA cycle and small molecules antioxidant capacity (SMAC) activities, while in vitro, the metabolic upregulation in all the studied pathways is limited. This altered metabolic pattern might be a consequence of cell exhaustion because of culture conditions, impeding cumulus cells to fulfil their role in providing proper support for acquiring oocyte competence.
SUMMARY SENTENCE: In vitro cultured mouse follicles exhibit altered glycolytic activity and redox metabolism in the somatic compartment during meiotic maturation.
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