Determinants of Oocyte Quality: Normal and Abnormal Ovarian Microenvironments

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Background

Mammals are born with a full complement of oocytes which are selected, developed, and ovulated during a female’s reproductive lifespan. The microenvironment of these oocytes are follicles that consist of supporting somatic cells, i.e., theca and granulosa cells, that provide essential nutrients and growth factors for optimal oocyte maturation. There is subsquent feedback communication from the oocyte to coordinate somatic cell and oocyte development. Over the course of a reproductive lifespan, oocytes are exposed to a myriad of stressors including toxins, inflammation, excess lipids, and oxidative stress. The use of artificial reproductive technologies (ART), like in vitro fertilization, also expose the oocyte to a culture environment which mimics but does not completely replicate the in vivo environment. Each of these stressors impinge on normal development and maturation of the oocyte which can lead to poor rates of embryonic development and/or induce structural or functional abnormalities during fetal development.



Important steps in oocyte growth and maturation include regulation of meiosis and chromatin conformation, changes in the number and localization of mitochondria and endoplasmic reticulum, transcriptional and post-transcriptional regulation of oocyte mRNA abundance, translation of oocyte mRNAs, and dynamic regulation of epigenetic modifications. Correlative and causative studies have demonstrated that each of these processes are necessary for normal embryonic development. It is also well documented that consequences of an abnormal oocyte microenvironment include DNA damage, misaligned chromosomes, endoplasmic reticulum stress, functional abnormalities in mitochondria, and differential abundance of oocyte mRNAs. Despite these advances, there remain knowledge gaps regarding the normal regulatory mechanisms at play during oocyte growth and development, especially at key milestones. How stress inducing factors alter the normal regulatory mechanisms are also unclear. These gaps are due in part to the limited amount of material available per sample and the sensitivity of molecular and cellular assays. Recent advances in the accuracy and quantitative capabilities of RNA sequencing, fluorescent in situ hybridization, immunoprecipitation, and immunofluorescence as well as new experimental models including non-human primates and domestic livestock have the potential to fill important existing gaps.



This Research Topic solicits Original Research papers and up-to-date Reviews that investigate cell signaling pathways, intraovarian factors, DNA dynamics, organelle structure, function and localization, and oocyte mRNA expression and stability during growth and maturation of the oocyte within a normal ovarian microenvironment. Manuscripts demonstrating how ovarian aging, subclinical inflammation, heat stress, metabolic dysfunction, toxins and endocrine disruptors, and in vitro culture during ART impact normal oocyte growth and maturation are also within the focus of the topic. Studies using rodent models, domestic livestock, and/or non-human primates are encouraged.

Keywords: Oncofertility, Toxicology, PCOS, Obesity, Heat Stress, Inflammation, Artificial Reproductive Technologies, Meiosis, Cytoplasmic Maturation

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