Transcriptome meta-analysis of three follicular compartments and its correlation with ovarian follicle maturity and oocyte developmental competence in cows

Abstract

Sirard MA. Transcriptome meta-analysis of three follicular compartments and its correlation with ovarian follicle maturity and oocyte developmental competence in cows. Physiol Genomics 48: 633-643, 2016. First published July 8, 2016 doi:10.1152/physiolgenomics.00050.2016.-Oocyte developmental competence in superstimulated cows is dependent in part on the duration of the FSH coasting. FSH coasting refers to superstimulation with FSH (2 days of endogenous FSH following follicle ablation and 3 days of FSH injections) followed by no FSH for a specific duration. The optimal duration varies among individuals. FSH coasting appears to modulate the transcriptome of different follicular compartments, which cooperate as a single functional unit. However, the integrative effects of FSH coasting on different follicular compartments remain ambiguous. Meta-analysis of three independent transcriptome studies, each focused on a single cell type (granulosa, cumulus, and oocyte) during FSH coasting, allowed the identification of 12 gene clusters with similar time-course expression patterns in all three compartments. Network analysis identified HNF4A (involved in metabolic functions) and ELAVL1 (an RNA-binding protein) as hub genes regulated respectively upward and downward in the clusters enriched at the optimal coasting time, and APP (involved in mitochondrial functions) and COPS5 (a member of the COP9 signalosome) as hub genes regulated respectively upwards and downwards in the clusters enriched progressively throughout the coasting period. We confirmed the effects on HNF4A downstream targets (TTR, PPL) and other hub genes (ELAVL1, APP, MYC, and PGR) in 30 cows with RT-quantitative PCR. The correlation of hub gene expression levels with FSH coasting indicated that a combination of these genes could predict oocyte competence with 83% sensitivity, suggesting that they are potential biomarkers of follicle differentiation. These findings could be used to optimize FSH coasting on an individual basis. ovarian follicle; oocyte competence; transcriptomics; meta-analysis; FSH coasting ASSISTED REPRODUCTIVE TECHNOLOGIES have been used successfully in a wide range of research and clinical applications. However, the success rate remains low, despite increasing research efforts (19). Better understanding of ovarian physiology and of the acquisition of oocyte developmental competence in particular is needed to improve the efficiency of fertility treatments in the clinical setting and in livestock production.

Genes of cellular components of morphogenesis in porcine oocytes before and after IVM

“…The first group consisted of genes encoding proteins whose activity and function were found in the nervous system and its related processes such as neurite growth, plasticity development and axonal navigation. Aamyloid beta precursor protein (APP) is a protein mainly related to the formation of amyloid plaques in the brain of patients with Alzheimer's disease (Borel et al 2017), however, contribution to oocytes maturation cannot be excluded, especially since Khan and coworkers (2016), presented the correlation between different schemes of FSH superstimulation and APP expression levels in oocytes of cows, concluding that together with other genes APP could be a potential biomarker of follicle differentiation and predictor of oocyte competence (Khan et al 2016).…”

Significant Down-Regulation of “Biological Adhesion” Genes in Porcine Oocytes after IVM

“…The only gene indirectly linked to oocyte maturation was APP , responsible for amyloid plaques formation in the brain of patients with Alzheimer’s disease [ 67 ]. Khan et al (2016) hypothesized APP could be a potential biomarker of follicle differentiation and predictor of oocyte competence in cows, since they found association between diverse FSH doses and APP expression levels in oocytes [ 76 ].…”

Folliculogenesis and acquisition of oocyte competence in cows

“…The dominant follicle will survive this decrease in FSH level by developing sensitive LH receptors that will maintain the growth and prevent atresia, compared to the subordinate follicles that will stop and progressively enter the atresia process within 1-2 days. This period of time during folliculogenesis seems important to prepare the granulosa cells for the major change that will occur at ovulation, the modification from an epithelial cell type into a mesenchymal cell type within the future corpus luteum (Khan et al, 2016a). If the basal LH is removed by using GnRH antagonist, a different gene expression condition will emerge (Sirard, 2016) and oocyte quality will decrease rapidly as in atretic follicles .…”