Cumulus Cell Genes as Potential Biomarkers of Oocyte and Embryo Developmental Competence

Shepel, Elena; Voznesenskaya, T. Yu.; Blashkiv, T. V.; Yanchii, R. I.

doi:10.15407/fz62.01.107

Cited by 6 publications

(2 citation statements)

References 31 publications

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“…Therefore, the production of hyaluronan is necessary for cumulus expansion [6]. HAS2 was suggested as potential biomarkers in CCs for selection of oocytes and embryos in the IVF program [7].…”

Section: Introductionmentioning

confidence: 99%

HAS2-AS1 is a novel LH/hCG target gene regulating HAS2 expression and enhancing cumulus cells migration

et al. 2019

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Background The cumulus expansion process is one of the LH mediated ovulatory processes. Hyaluronan synthase 2 (HAS2) regulates the synthesis of hyaluronic acid, the main component of the cumulus expansion process. Recently, the lncRNA HAS2 antisense RNA 1 (HAS2-AS1) was identified in our global transcriptome RNA-sequencing of novel ovulation associated genes. The role of HAS2-AS1 in HAS2 regulation w.as studied previously with contradictive results in different models but not in the ovary. Taken together the induction of HAS2-AS1 and the important role of HAS2 in the cumulus expansion process, we hypothesize that HAS2-AS1 regulate HAS2 expression and function in the ovary. Therefore we undertook to study the expression, regulation, and possible functional role of HAS2-AS1 in the human ovary. Results HAS2-AS1, located within the HAS2 gene that was highly regulated in our library. We found that HAS2-AS1 express mainly in cumulus cells (CCs). Furthermore, HAS2-AS1 showed low expression in immature CCs and a significant increase expression in mature CCs. Functional studies reveal that inhibition of HAS2-AS1 by siRNA caused decrease expression of HAS2. Furthermore, inhibition of HAS2-AS1 by siRNA results in decrease migration of granulosa cells. Conclusions Our results suggest that HAS2-AS1 is an LH/hCG target gene that plays a positive role in HAS2 expression and thus might play a role in regulating cumulus expansion and migration.

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Section: Introductionmentioning

confidence: 99%

HAS2-AS1 is a novel LH/hCG target gene regulating HAS2 expression and enhancing cumulus cells migration

et al. 2019

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“…Cumulus cells, surrounding the oocytes, are important key contributors towards oocyte development, paving the way to using gene expression in cumulus cells as potential biomarkers. Over the years, more than one hundred genes have been identified and linked with embryo development, pregnancy and live birth ( [3,8,16,18,23]; for a recent review [32]). However, only a few gene sets have been studied in more detail.…”

Section: Introductionmentioning

confidence: 99%

Improved clinical outcomes after non-invasive oocyte selection and Day 3 eSET in ICSI patients

Vaerenbergh

Adriaenssens

Coucke³

et al. 2021

Reprod Biol Endocrinol

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Background Non-invasive oocyte quality scoring, based on cumulus gene expression analysis, in combination with morphology scoring, can increase the clinical pregnancy (CPR) and live birth rates (LBR) in Day 3 eSET (elective single embryo transfer) ICSI patients. This was first investigated in a pilot study and is now confirmed in a large patient cohort of 633 patients. It was investigated whether CPR, LBR and time-to-pregnancy could be improved by analyzing the gene expression profile of three predictive genes in the cumulus cells, compared to patients with morphology-based embryo selection only. Methods A large interventional, non-randomized, assessor-blinded cohort study with 633 ICSI patients was conducted in a tertiary fertility center. Non-PCOS patients, 22–39 years old, with good ovarian reserve, were stimulated with HP-hMG using a GnRH antagonist protocol and planned for fresh Day 3 eSET. The cumulus cells from individually denuded oocytes were ranked by a lab-developed cumulus cell test: qRT-PCR for three predictive genes (CAMK1D, EFNB2 and SASH1) and two control genes (UBC, B2M). The embryo selected for transfer was highest ranked from the pool of morphologically transferable Day 3 embryos. Patients in the control (n = 520) and experimental arm (n = 113) were compared for clinical pregnancy and live birth, using a weighted generalized linear model, and time-to-pregnancy using Kaplan-Meier curves. Results The CPR was 61% in the experimental arm (n = 113) vs 29% in the control arm (n = 520, p < 0.0001). The LBR in the experimental arm (50%) was significantly higher than in the control arm (27%,p < 0.0001). Time-to-pregnancy was significantly shortened by 3 transfer cycles independent of the number of embryos available on Day 3 (Kaplan-Meier, p < 0.0001). Cumulus cell tested patients < 35 years (n = 65) or ≥ 35 years (n = 48) had a CPR of 62 and 60% respectively (ns). For cumulus cell tested patients with 2, 3–4, or > 4 transferable embryos, the CPR was 66, 52, and 67% (ns) respectively, and thus independent of the number of transferable embryos on Day 3. Conclusions This study provides further evidence of the clinical usefulness of the non-invasive cumulus cell test over time in a larger patient cohort. Trial registration Clinicaltrials.gov, NCT03659786/NCT02962466 (Registered 6Sep2018/11Nov2016, retrospectively registered.

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Oxidative stress markers in the follicular fluid of patients with polycystic ovary syndrome correlate with a decrease in embryo quality

Liu

Zhao

et al. 2020

J Assist Reprod Genet

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Cumulus Cell Genes as Potential Biomarkers of Oocyte and Embryo Developmental Competence

Cited by 6 publications

References 31 publications

HAS2-AS1 is a novel LH/hCG target gene regulating HAS2 expression and enhancing cumulus cells migration

HAS2-AS1 is a novel LH/hCG target gene regulating HAS2 expression and enhancing cumulus cells migration

Improved clinical outcomes after non-invasive oocyte selection and Day 3 eSET in ICSI patients

Oxidative stress markers in the follicular fluid of patients with polycystic ovary syndrome correlate with a decrease in embryo quality

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