Extensive effects of in vitro oocyte maturation on rhesus monkey cumulus cell transcriptome

Abstract

Lee YS, VandeVoort CA, Gaughan JP, Midic U, Obradovic Z, Latham KE. Extensive effects of in vitro oocyte maturation on rhesus monkey cumulus cell transcriptome. Am J Physiol Endocrinol Metab 301: E196 -E209, 2011. First published April 12, 2011 doi:10.1152/ajpendo.00686.2010.-The elaboration of a quality oocyte is integrally linked to the correct developmental progression of cumulus cell phenotype. In humans and nonhuman primates, oocyte quality is diminished with in vitro maturation. To determine the changes in gene expression in rhesus monkey cumulus cells (CC) that occur during the final day prior to oocyte maturation and how these changes differ between in vitro (IVM) and in vivo maturation (VVM), we completed a detailed comparison of transcriptomes using the Affymetrix gene array. We observed a large number of genes differing in expression when comparing IVM-CC and VVM-CC directly but a much larger number of differences when comparing the transitions from the prematuration to the post-IVM and post-VVM states. We observed a truncation or delay in the normal pattern of gene regulation but also remarkable compensatory changes in gene expression during IVM. Among the genes affected by IVM are those that contribute to productive cell-cell interactions between cumulus cell and oocyte and between cumulus cells. Numerous genes involved in lipid metabolism are incorrectly regulated during IVM, and the synthesis of sex hormones appears not to be suppressed during IVM. We identified a panel of 24 marker genes, the expression of which should provide the foundation for understanding how IVM can be improved for monitoring IVM conditions and for diagnosing oocyte quality. oocyte quality; in vitro maturation LIFE BEGINS IN THE OOCYTE. The oocyte accumulates a remarkable and complex macromolecular reservoir that mediates and controls the initial development of each new individual while at the same time eliminating a range of molecules that promote gametogenesis but would otherwise impede early embryogenesis (8,36,37,67). Failure to complete these transitions appropriately yields an oocyte with limited developmental potential, unable to undergo fertilization or activation, or unable to sustain embryogenesis after fertilization and activation.Because of the key role of the oocyte in early development, understanding the molecular features that confer a high oocyte developmental potential is of paramount importance in reproductive biology. Such information will reveal the underlying mechanisms and processes that drive oogenesis and early embryogenesis. Moreover, such information will provide markers with which to screen and select high-quality oocytes for assisted reproduction in humans and could enhance success in agricultural reproductive biology and species conservation applications.The oocyte develops in close coordination with the somatic companion cells, particularly the cumulus oophorous cells, which maintain direct contact with the oocyte via transzonal processes and gap junctions until ovulation. Through its secretion...

Characterization of the human cumulus cell transcriptome during final follicular maturation and ovulation

“…These changes demonstrate the shift of CCs from the immature proliferating stage toward a more specialized mature condition. Our results are similar to results obtained in animal models including mouse, bovine and primates (HernandezGonzalez et al, 2006;Lee et al, 2011;Regassa et al, 2011;Xu et al, 2011).…”

“…We also validated the RNAseq results using qPCR in over 25 different genes of known and unknown ovarian function. Cumulus cell transcriptome during follicular maturation Lee et al (2011) performed a microarray analysis of the cumulus transcriptome during in vivo maturation and IVM of rhesus monkey oocytes. They described 71 genes that significantly changed by .10-fold during in vivo maturation of oocytes.…”

“…In a rhesus monkey transcriptome study, a large number of genes were oppositely regulated in IVM compared with IVF (Lee et al, 2011). The human CC transcriptome after IVF differs significantly from the CC transcriptome after IVM (Ouandaogo et al, 2012).…”

“…Several human and primate studies have indicated that the CC transcriptome is dysregulated during the IVM process (Lee et al, 2011;Ouandaogo et al, 2012;Guzman et al, 2013). In a rhesus monkey transcriptome study, a large number of genes were oppositely regulated in IVM compared with IVF (Lee et al, 2011).…”

Lipids and oocyte developmental competence: the role of fatty acids and β-oxidation

“…b-oxidation (oxidation of 14 C-palmitic acid) in cat oocytes maturing in vitro was significantly less than oocytes that had matured in vivo (Spindler et al 2000). In rhesus monkey, microarray analysis found that several lipid metabolism genes, including some involved in b-oxidation, were dysregulated in cumulus cells R22 K R Dunning and others following IVM compared with those matured in vivo (Lee et al 2011). In porcine oocytes, levels of ACSL3 and ACADL, which activate long-chain fatty acids before their entry into mitochondria and catalyse the first step in the b-oxidation spiral respectively, were found to be dysregulated in another model of poor oocyte developmental competence (Yuan et al 2011).…”