Next-Generation Sequencing Reveals Downregulation of the Wnt Signaling Pathway in Human Dysmature Cumulus Cells as a Hallmark for Evaluating Oocyte Quality

Abstract

Background: Dysmature cumulus cells are lower fertilization rates and abnormalities in embryonic development compared to maturation cumulus cells. Morphological evaluation of cumulus–oocyte complexes (COCs) considered the possibility that differences may also be found in gene expression. Purpose: To identify hallmarks for evaluating oocyte quality by investigating gene expression patterns in human cumulus cells surrounding oocytes. Methods: Cumulus cells were obtained from the cumulus–oocyte complex of infertile women treated with assisted reproductive technology. Based on maturity level, the cumulus cells were classified into two categories, i.e., dysmature cumulus cell (DCC) and maturation cumulus cell. DCCs were subjected to gene expression analysis using next-generation sequencing and compared with COCs that are in the process of maturation as controls. Results: The expression levels of genes involved in the Wnt signal/β-catenin pathway were significantly reduced in DCCs compared with those in control cells. Moreover, the expression levels of genes involved in multiple pathways associated with apoptosis were also significantly reduced compared with those in control cells. Conclusions: DCCs showed significant decreases in apoptosis- and Wnt/β-catenin signaling-associated gene expression. DCCs could be classified by morphological evaluation, and the method described in this study may be useful as an oocyte quality estimation tool.

The influence of ovarian follicular niche on oocyte development

“…Summarizing, the GSK3β inhibition suggests an increase in MII oocytes incompetent to develop to the blastocyst stage, that had an also increased β-catenin localization in the cumulus cells nuclei after maturation. Altogether, these characteristics exhibited by the CHIR group are similar to that previously shown in human in vivo matured oocyte uncapable to develop to embryos and referred as dysmature oocytes, a term also used describe their respective follicles (AKINO et al, 2020;KANG et al, 2022;LOBO;DIZEREGA;MARRS, 1985).…”

“…In view of our developmental results, we considered a validation of effectiveness of the CHIR99021 in the COCs. Thus, a experiment using immunostaining for β-catenin, a canonical member of the Wnt signaling pathway and related to the GSK3β activity (AKINO et al, 2020;ASUNI et al, 2006), were performed in matured COC under 3 previously described conditions (CTL, CHIR and DKK1) and also in intact immature COCs immediately fixed after aspiration.…”

The association of the expression of RBX1 and BAMBI in polycystic ovarian syndrome patients' cumulus cells and oocyte maturation

“…The WNT signaling pathway plays an imperative role in normal ovarian function, fertility (9,19), and development of follicles (9,20), as well as during embryogenesis (21). Akino and colleagues (22) showed that the dysregulation of this pathway in cumulus cells can result in follicle atresia, a reduced fertilization rate, and abnormal embryogenesis. The Wnt/β-catenin pathway is initiated when a ligand binds to the low-density lipoprotein receptor-related protein 5/6 (LRP5/6) and the Frizzled receptor.…”

Multi-Omics Analysis and Machine Learning Prediction Model for Pregnancy Outcomes After Intracytoplasmic Sperm Injection–in vitro Fertilization

“…WNT5A is a crucial mediator of the Hedgehog and Wnt signaling pathways that may regulate the formation of primordial germ cells. Akino et al showed that the transcription levels of WNT9B/WNT10B/ Frizzled-7/ AXIN2 , which are involved in the Wnt signal/β-catenin pathway, were significantly lower in human dysmature CCs than in control cells ( 27 ). Habara et al revealed that Wnt signaling is pivotal for primordial follicle activation due to regulation of the differentiation of pre-granulosa cells and subsequent oocyte maturation, which is another indicator of how Wnt signaling exerts an effect on oocyte quality and subfertility ( 28 ).…”