Oogenesis

With the nucleus as an exception, mitochondria are the only animal cell organelles containing their own genetic information, called mitochondrial DNA (mtDNA). During oocyte maturation, the mtDNA copy number dramatically increases and the distribution of mitochondria changes significantly. As oocyte maturation requires a large amount of ATP for continuous transcription and translation, the availability of the right number of functional mitochondria is crucial. There is a correlation between the quality of oocytes and both the amount of mtDNA and the amount of ATP. Suboptimal conditions of in vitro maturation (IVM) might lead to changes in the mitochondrial morphology as well as alternations in the expression of genes encoding proteins associated with mitochondrial function. Dysfunctional mitochondria have a lower ability to counteract reactive oxygen species (ROS) production which leads to oxidative stress. The mitochondrial function might be improved with the application of antioxidants and significant expectations are laid on the development of new IVM systems supplemented with mitochondria-targeted reagents. Different types of antioxidants have been tested already on animal models and human rescue IVM oocytes, showing promising results. This review focuses on the recent observations on oocytes' intracellular mitochondrial distribution and on mitochondrial genomes during their maturation, both in vivo and in vitro. Recent mitochondrial supplementation studies, aiming to improve oocyte developmental potential, are summarized.

Cumulus cells (CCs) originating from undifferentiated granulosa cells (GCs) differentiate in mural granulosa cells (MGCs) and CCs during antrum formation in the follicle by the distribution of location. CCs are supporting cells of the oocyte that protect the oocyte from the microenvironment, which helps oocyte growth and maturation in the follicles. Bi-directional communications between an oocyte and CCs are necessary for the oocyte for the acquisition of maturation and early embryonic developmental competence following fertilization. Follicle-stimulation hormone (FSH) and luteinizing hormone (LH) surges lead to the synthesis of an extracellular matrix in CCs, and CCs undergo expansion to assist meiotic resumption of the oocyte. The function of CCs is involved in the completion of oocyte meiotic maturation and ovulation, fertilization, and subsequent early embryo development. Therefore, understanding the function of CCs during follicular development may be helpful for predicting oocyte quality and subsequent embryonic development competence, as well as pregnancy outcomes in the field of reproductive medicine and assisted reproductive technology (ART) for infertility treatment.

Oocyte in vitro maturation (IVM) is an assisted reproductive technology designed to obtain mature oocytes following culture of immature cumulus-oocyte complexes collected from antral follicles. Although IVM has been practiced for decades and is no longer considered experimental, the uptake of IVM in clinical practice is currently limited. The purpose of this review is to ensure reproductive medicine professionals understand the appropriate use of IVM drawn from the best available evidence supporting its clinical potential and safety in selected patient groups. This group of scientists and fertility specialists, with expertise in IVM in the ART laboratory and/or clinic, explore here the development of IVM towards acquisition of a non-experimental status and, in addition, critically appraise the current and future role of IVM in human ART.

Folliculogenesis is a complex, multi-stage process crucial for the establishment and maintenance of female fertility through the production of a developmentally competent oocyte. Folliculogenesis, including follicular formation, activation, growth and maturation, relies on a finely tuned spatiotemporal crosstalk between germ cells, somatic cells, and the hypothalamic-pituitary-ovarian axis. This work provides a comprehensive overview of the cellular dynamics and molecular mechanisms underlying each stage of follicular development. A particular emphasis is placed on the interaction of growth factors, transcriptional networks, signaling pathways and endocrine cues that collectively govern follicular fate and oocyte quality. Disruptions in these interactions lead to emergence of pathological conditions such as premature ovarian insufficiency and age-related infertility. We further highlight the dual aspects of oocyte maturation, nuclear and cytoplasmic, as major determinants of developmental competence, and explore the role of spindle dynamics, organelle redistribution and epigenetic reprograming in this process. The bidirectional communication between oocytes and cumulus cells, mediated by paracrine signaling and jap junctions, is underscored as a pivotal regulator of oocyte metabolic activity, redox homeostasis, and meiotic competence. A better understanding of the oocyte-cumulus cell interaction offers new approaches for refining the in vitro maturation systems and improving assisted reproductive technologies. A special attention is given to the emerging use of cumulus cell-derived biomarkers for noninvasive assessment of oocyte quality and prediction of preimplantation embryo development. Taken together, this article presents an integrated framework to guide future research in reproductive biology, regenerative medicine, and fertility preservation.