The key role of cumulus cells in oocytes in vitro maturation protocols

Abstract

The only strategy that can completely circumvent complications associated with conventional in vitro fertilization is in vitro maturation (IVM) of oocytes. This technique can contribute to fertility preservation programs, where time constraints and/or health risks limit the use of controlled ovarian hyperstimulation for in vitro fertilization/intracytoplasmic sperm injection (1Jurema M.W. Nogueira D. In vitro maturation of human oocytes for assisted reproduction.Fertil Steril. 2006; 86: 1277-1291Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar). There is a need to characterize competence in human oocytes because low maturation rates in IVM systems suggest that a considerable proportion of retrieved oocytes are still meiotically incompetent. Venturas et al. (2Venturas M. Yang X. Kumar K. Wells D. Racowsky C. Needleman D.J. Metabolic imaging of human cumulus cells reveals associations among metabolic profiles of cumulus cells, patient clinical factors, and oocyte maturity.Fertil Steril. 2021; 116: 1651-1662Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar) showed that the assessment of cumulus cell (CC) clusters obtained from patients undergoing assisted reproductive technology treatment using fluorescence lifetime imaging microscopy (FLIM) could be a good strategy to predict oocyte quality. It is significant to remark that this method is noninvasive. The study demonstrated the metabolic association between CCs and oocytes. The measurements of the metabolic state (NAD(P)H and FAD+ coenzymes) of CCs by FLIM imaging were correlated with oocyte maturation, patient age, and antimüllerian hormone (AMH) (2Venturas M. Yang X. Kumar K. Wells D. Racowsky C. Needleman D.J. Metabolic imaging of human cumulus cells reveals associations among metabolic profiles of cumulus cells, patient clinical factors, and oocyte maturity.Fertil Steril. 2021; 116: 1651-1662Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar). Various studies have described the key role of CCs in oocyte maturation, ovulation, and fertilization. It has been established that CC damage produces low fertilization and blastocyst rates (3Corn C.M. Hauser-Kronberger C. Moser M. Tews G. Ebner T. Predictive value of cumulus cell apoptosis with regard to blastocyst development of corresponding gametes.Fertil Steril. 2005; 84: 627-633Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar). The close contact between CCs and oocytes through gap junctions allows the bidirectional interchange of molecules regulating nucleus and cytoplasm oocyte maturation, oocyte quality, and subsequent embryo development (4Tanghe S. Van Soom A. Nauwynck H. Coryn M. de Kruif A. Minireview: functions of the cumulus oophorus during oocyte maturation, ovulation, and fertilization.Mol Reprod Dev. 2002; 61: 414-424Crossref PubMed Scopus (389) Google Scholar). In addition, the presence of CCs during IVM was found to be effective in regulating the synthesis and concentration of significant cytoplasmic factors such as glutathione and Ca2+. During oocyte IVM, CCs undergo a molecular maturation process concomitantly with oocyte nuclear maturation. In turn, the CC gene expression profile varies according to the stages of oocyte maturation (5Ouandaogo Z.G. Haouzi D. Assou S. Dechaud H. Kadoch I.J. De Vos J. et al.Human cumulus cells molecular signature in relation to oocyte nuclear maturity stage.PLoS One. 2011; 6e27179Crossref PubMed Scopus (63) Google Scholar). Additionally, oocytes actively regulate fundamental aspects of CC function via oocyte-secreted factors, controlling the complex CC microenvironment. The beneficial effect of CCs during oocyte growth to stimulate competence acquisition and further support embryonic development is, therefore, unequivocal. The fact that there are measurable differences between CCs associated with individual oocytes highlights the potential use of FLIM to determine oocyte-specific characteristics. Variations in FLIM parameters associated with differences between patients indicate that patient-specific factors impact on CC metabolism. Metabolic imaging correlations with patient age and AMH remained significant while controlling for either of these two patient characteristics, although the metabolic variance between patients detected by FLIM was not entirely because of age or AMH alone, suggesting that other patient characteristics affect CC metabolic function. The description of human CC–oocyte interactions using the FLIM technique could be a promising approach for IVM protocols. Future works should investigate other clinical factors. This work was supported by grants from Agencia Nacional de Promoción Científica y Tecnológica de la República Argentina (PICT BID 2019-1180) Ministerio de Ciencia, Tecnología e Innovación Productiva de la Nación Argentina. The author thanks Adriana Di Maggio for careful manuscript correction. Relationship between semen regurgitation and pregnancy rates with intrauterine inseminationFertility and SterilityVol. 116Issue 6PreviewTo evaluate the relationship between semen regurgitation and intrauterine insemination (IUI) outcomes. We hypothesized that clinical pregnancy rates and live birth rates would be reduced when regurgitation occurred. Full-Text PDF Open Archive