Analyzing the Transcriptome Profile of Human Cumulus Cells Related to Embryo Quality via RNA Sequencing

Abstract

Selecting excellent oocytes is required to improve the outcomes of in vitro fertilization (IVF). Cumulus cells (CCs) are an integral part of the oocyte maturation process. Therefore, we sought to identify differentially expressed genes in CCs to assess oocyte quality and embryo development potential. We divided the participants' embryos into the high-quality embryo group and low-quality embryo group by the information including age, body mass index, and the levels of luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone. We analyzed a total of 7 CC samples after the quality control in RNA sequencing. We found that 2499 genes were unregulated and 5739 genes were downregulated in high-quality embryo group compared to the low-quality embryo group (Padj < 0.05). Interestingly, MSTN, CTGF, NDUFA1, VCAN, SCD5, and STAR were significantly associated with the quality of embryo. In accordance with the results of RNA sequencing, the association of the expression levels of MSTN, CTGF, NDUFA1, VCAN, SCD5, and STAR with the embryo quality was verified by quantitative reverse-transcription polymerase chain reaction (RT-qPCR) in 50 CC samples. Despite the small sample size and lack of validation in animal models, our study supports the fact that differential gene expression profile of human CCs, including MSTN, CTGF, NDUFA1, VCAN, SCD5, and STAR, can serve as potential indicator for embryo quality.

Equine chorionic gonadotropin drives the transcriptional profile of immature cumulus‐oocyte complexes and in vitro‐produced blastocysts of superstimulated Nelore cows

“…The eCG uses also upregulated the methyltransferases ( Oocyte imprints seems to be established in later oocyte development stages (Lucifero, Mertineit, Clarke, Bestor, & Trasler, 2002;Obata & Kono, 2002;Obata et al, 1998;Tada et al, 2000) which could be linked with the higher expression previous found of these three DNMTs in mouse (Uysal, Ozturk, & Akkoyunlu, 2017) Furthermore, we found that NDUFA1, a mitochondrial antioxidant enzyme that is expressed in response to oxidative and endoplasmic reticulum stresses, that was upregulated in human cumulus cells from oocytes yielding low-quality embryos and from oocytes failing in fertilization (Liu et al, 2018), and was 300-fold downregulated in the FSH/eCG group.…”

“…CPT1B , an enzyme required for the net transport of long‐chain fatty acyl‐CoAs from the cytoplasm into the mitochondria to for β‐oxidation fate, and VCAN , an extracellular matrix proteoglycan and a key biomarker of pregnancy outcome (Gebhardt, Feil, Dunning, Lane, & Russell, ; Kusano, Tsujihara, Masui, Kozai, & Takeuchi, ; Russell, Doyle, Ochsner, Sandy, & Richards, ; Wathlet et al, ; Xu, Chen, Zhang, Wei, & Cao, ),were upregulated in the FSH/eCG group. Furthermore, we found that NDUFA1 , a mitochondrial antioxidant enzyme that is expressed in response to oxidative and endoplasmic reticulum stresses, that was upregulated in human cumulus cells from oocytes yielding low‐quality embryos and from oocytes failing in fertilization (Liu et al, ), and was 300‐fold downregulated in the FSH/eCG group.…”

Periovulatory insulin signaling is essential for ovulation, granulosa cell differentiation, and female fertility

“…thought to modulate cell proliferation and apoptosis, although its mechanism of action is unclear. 55 In addition, transcriptome profiling of human CGCs revealed that VCAN was positively associated with embryo quality, 74 which may contribute to the retarded development we observe in IR-CKO blastocysts. Another putative TCF3-regulated factor of relevance is Secretogranin II (SCG2), which is induced in granulosa cells during the periovulatory window.…”

Omics and Artificial Intelligence to Improve In Vitro Fertilization (IVF) Success: A Proposed Protocol

“…A recent study, among many others, showed the connection between the CCs transcriptomic profile and embryo quality. Authors reported that the differential gene expression profile of human CCs, including MSTN, CTGF, NDUFA1, VCAN, SCD5 and STAR, can be used as potential indicators of embryo quality [ 24 ]. Thus, the parameters analyzed provide an indication of the competence and quality of the oocyte through positive and negative association with the gene expression profile and, furthermore, may act as positive/negative predictors of the embryo quality itself and pregnancy outcome.…”