Differential gene expression in cumulus cells as a prognostic indicator of embryo viability: a microarray analysis

Abstract

Besides the established selection criteria based on embryo morphology and blastomere number, new parameters for embryo viability are needed to improve the clinical outcome of IVF and more particular of elective single-embryo transfer. Genome-wide gene expression in cumulus cells was studied, since these cells surround the oocyte inside the follicle and therefore possibly reflect oocyte developmental potential. Early cleavage (EC) was chosen as a parameter for embryo viability. Gene expression in cumulus cells from eight oocytes resulting in an EC embryo (EC-CC; n = 8) and from eight oocytes resulting in a non-EC (NEC) embryo (NEC-CC; n = 8) was analysed using microarrays (n = 16). A total of 611 genes were differentially expressed (P < 0.01), mainly involved in cell cycle, angiogenesis, apoptosis, epidermal growth factor, fibroblast growth factor and platelet-derived growth factor signalling, general vesicle transport and chemokine and cytokine signalling. Of the 25 selected differentially expressed genes analysed by quantitative real-time PCR 15 (60%) genes could be validated in the original samples. Of these 8 (53%) could also be validated in 24 (12-EC-CC and 12 NEC-CC) extra independent samples. The most differentially expressed genes among these were CCND2, CXCR4, GPX3, CTNND1 DHCR7, DVL3, HSPB1 and TRIM28, which probably point to hypoxic conditions or a delayed oocyte maturation in NEC-CC samples. This opens up perspectives for new molecular embryo or oocyte selection parameters which might also be useful in countries where the selection has to be made at the oocyte stage before fertilization instead of at the embryonic stage.

Mice overexpression of <i>human augmenter of liver regeneration</i> (hALR) in male germ cells shows abnormal spermatogenesis and reduced fertility

“…The expression of Kit, which marks the germ cells prior to preleptotene [29], did not exhibit significantly different expression patterns either. The expression of Ldhc4, a gene restricted to the mid/late-pachytene spermatocytes [30], was markedly increased in the transgenic mice testes, whereas the expression of Dvl1, a gene activated in round, elongating, and elongated spermatids [31,32], tended to be far weaker in the transgenic mice testes, consistent with our morphological observations. These observations confirm that transgenic mice fail to complete spermatogenesis, the process being specifically arrested at the stage of pachytene spermatocytes.…”

Cumulus cell gene expression following the LH surge in bovine preovulatory follicles: potential early markers of oocyte competence

“…1). Moreover, expression of apoptosis-related genes in CCs reported herein was also associated with oocyte final maturation progression in several previous studies in many mammalian species (Host et al 2002, van Montfoort et al 2008, and it was even suggested as an indicator to predict human oocyte quality (Lee et al 2001). However, at this stage (GVBD), the CCs tissue maintains a proliferative phenotype (cell cycle and cellular growth functions) that prepares the prerequisite structure for rapid expansion and oocyte competence acquisition support.…”

Differences in cumulus cells gene expression between modified natural and stimulated in vitro fertilization cycles

“…GPX3 catalyzes the reduction of free hydrogen peroxide, organic hydroperoxide and lipid peroxides and protects cells against oxidative damage [39]. GPX3 has also been proposed to be a marker of poor embryo quality as it was down-regulated in CC of early-cleaving embryos and up-regulated in CC of nonearly cleaving embryos [40]. Glutathione (GSH) function in oocytes is mainly related to antioxidative properties [41] furthermore, it protects the oocyte's meiotic spindle against oxidative damage [42].…”