To study the relationship between the expression of 10 selected genes in cumulus cells and the corresponding oocyte development competence, and the effect of patient age and body mass index on gene expression of cumulus cells, we collected 354 cumulus cell masses associated with individual oocyte from 48 women. The expression levels of the genes involved in glucose metabolism (PFKP, PKM2, LDHA and GFPT) and expansion (HAS2, VCAN, TNFAIP6, PTGS2, PTX3 and SDC4) in cumulus cells were detected by reverse transcription polymerase chain reaction. These were compared among oocyte maturity, fertilization, embryo morphology and implantation, and analyzed the effect of the subject's age and body mass index. Cumulus cell PFKP expression from mature oocytes was higher than those from immature oocytes (P = 0.014), and VCAN expression was higher from oocytes that developed into high-quality embryos (P = 0.024). TNFAIP6 expression in cumulus cells from fertilized oocytes was lower than that from unfertilized oocytes (P = 0.044). The levels of VCAN, TNFAIP6, PTX3 and SDC4 were changed significantly as a function of the subject's age and body mass index. In conclusion, the level of VCAN expression in cumulus cells is positively correlated with the early embryo morphology score, and with further development could perhaps be used to evaluate oocyte developmental competence to complement embryonic morphological assessment.
Mitophagy is the process by which cells selectively remove supernumerary or damaged mitochondria through autophagy, and is crucial for mitochondrial homeostasis and cell survival. Mitochondria play vital roles in determining the developmental competence of oocytes. During the early stages of oogenesis, aberrant mitochondria can be removed by mitophagy. After oocyte formation, mitophagy is not actively initiated to clear damaged mitochondria despite the presence of mitophagy regulators in oocytes, which leads to the transmission of dysfunctional mitochondria from the oocyte to the embryo. However, granulosa cells around oocytes can improve mitochondrial function through mitophagy, thereby improving oocyte developmental capacity. Furthermore, this review discusses recent work on the substances and environmental conditions that affect mitophagy in oocytes and granulosa cells, thus providing new directions for improving oocyte quality during assisted reproductive technology treatment.
Extracellular vesicles (EVs), present in cell culture media and several body fluids, play a prominent role in intercellular communication under physiological and pathological conditions. We performed a systematic literature search to review evidence regarding the existence, composition, and release of different EVs, as well as the biomarkers, cargos, and separation methods. We also reviewed the potential of EVs to transport cargos and alter the function and phenotype of recipient cells associated with aging and reproductive diseases, including polycystic ovary syndrome and endometriosis. In aging, EVs promote inflammatory reactions and offsetting the occurrence of aging. In the polycystic ovary syndrome and endometriosis, EVs and their cargos are involved in the occurrence of diseases, therapeutic strategies, and perform as non-invasive biomarkers. As the study of EVs is still in the early stages, it is not surprising that most of the current literature only describes their possible roles.
Background Cell-free mitochondrial DNA (cf-mtDNA) in body fluids has attracted much attention for the purpose of monitoring disease because of the clinical advantages. This study investigated whether the cf-mtDNA content in human follicular fluid samples was associated with oocyte and embryo developmental competence. Methods We collected 225 individual follicular fluid samples from 92 patients undergoing conventional in vitro fertilization ( n = 53) or intracytoplasmic sperm injection ( n = 39). cf-mtDNA and cell-free nuclear DNA (cf-nDNA) were measured using real-time quantitative PCR for the ND1 and β -globin genes. Multivariate logistic regression and linear regression were used to analyze data. Results The relative cf-mtDNA content (cf-ND1/cf- β -globin ratio) in follicular fluid was significantly lower in the group showing blastocyst development than in the non-blastocyst group ( P = 0.030). Additionally, the relative cf-mtDNA content was significantly and positively correlated with the age of the female patient ( P = 0.009), while the relative cf-mtDNA content for older women (≥38 years old) with anti-Müllerian hormone (AMH) ≤1.1 ng/ml was significantly higher than in those with AMH > 1.1 ng/ml ( P <0.05). The cf-nDNA content was significantly positively correlated with the antral follicle count ( P = 0.012), and significantly negatively correlated with both the number of days of stimulation and the total dose of gonadotropin administration ( P = 0.039 and P = 0.015, respectively). Neither cf-mtDNA nor cf-nDNA levels in follicular fluid were associated with oocyte maturation, fertilization, or Day 3 embryo morphological scoring. Conclusions The relative cf-mtDNA content in human follicular fluid was negatively correlated with blastulation and positively correlated with the patient age, indicating that it is a promising bio-marker to evaluate oocyte developmental competence. Electronic supplementary material The online version of this article (10.1186/s12958-019-0495-6) contains supplementary material, which is available to authorized users.
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