Transcriptome analysis of ovine granulosa cells reveals differences between small antral follicles collected during the follicular and luteal phases

Ovarian follicular growth occurs in both the follicular and luteal phases of the estrous cycle but in very different endocrine contexts. In both phases, many small antral follicles with similar morphologic and histologic characteristics are present within the ovaries as a reserve for the terminal folliculogenesis. However, there are several gaps in our molecular knowledge of the gene expression profiles of small antral follicles in the follicular and luteal phases. The aim of the present study was to use RNA sequencing to compare and analyze the global transcriptional profile of ovine granulosa cells collected from small antral follicles (1-3 mm) either during the follicular or the luteal phase of the estrous cycle, with the hypothesis that they should be differential. We identified 663 genes whose mRNA was differentially expressed or accumulated in the granulosa cell layer of small antral follicles in the two phases. A comprehensive interpretation of these data was performed through integrative analyses (Gene Ontology, Ingenuity Pathway Analysis) and the exploitation of already available transcriptomic data on follicular growth and atresia. In particular, we observed that the contrasted endocrine context between follicular and luteal phases may have an impact on estradiol, follicle-stimulating hormone (FSH), and on the activin/inhibin signaling pathways. Furthermore, we reveal the possible initiation of early follicular atresia in small antral follicles during the follicular phase in interaction with the presence of immune cells. This study provides new insights into the gene expression profile in ovine granulosa cells, and we suggest that these molecular changes may have an implication at the time of follicle selection.