In the present study, there were 128, 263, and 139 differentially expressed genes (DEGs) from the ovary, pituitary, and hypothalamus, respectively, with the FecB B+/FecB ++ genotype. Results indicated that there was a synchronized, and differential increase in mRNA transcript abundances for genes encoding for ovarian steroidogenesis-signaling proteins in the ovary, TGF-β-signaling in hypothalamus, cAMP-signaling-transduction, and dopaminergic-synapse pathways in the pituitary. The values for these variables were associated with mean prolificacy in indigenous sheep and results provided indications for candidate regulator proteins that coordinate processes related to prolificacy in ewes. Furthermore, the results when there was evaluation of the FecB-genotype-specific co-expression modules implied that CYP17 was the hub gene connecting the pathways and for modulation of folliculogenesis and ovulation in the ewe with the FecB B+ genotype.