Uterine leiomyomas are benign uterine tumors characterized by extracellular matrix remodeling, increased collagen deposition, and increased smooth mus

The metastatic spread of a tumor is dependent upon the ability of the tumor to stimulate surrounding stromal cells to express enzymes required for tissue remodeling. The immunoglobulin superfamily protein basigin (EMMPRIN/CD147) is a cell surface glycoprotein expressed by tumor cells that stimulates matrix metalloproteinase and vascular endothelial growth factor expression in stromal cells. The ability of basigin to stimulate expression of molecules involved in tissue remodeling and angiogenesis makes basigin a potential target for the development of strategies to block metastasis. However, the identity of the cell surface receptor for basigin remains controversial. The goal of this study was to determine the identity of the receptor for basigin. Using a novel recombinant basigin protein (rBSG) corresponding to the extracellular domain of basigin, it was demonstrated that the native, nonglycosylated rBSG protein forms dimers in solution. Furthermore, rBSG binds to the surface of uterine fibroblasts, activates the ERK1/2 signaling pathway, and induces expression of matrix metalloproteinases 1, 2, and 3. Proteins that interact with rBSG were isolated using a biotin label transfer technique and sequenced by matrix-assisted laser desorption ionization tandem mass spectrophotometry. The results demonstrate that rBSG interacts with basigin expressed on the surface of fibroblasts and is subsequently internalized. During internalization, rBSG associates with a novel form of human basigin (basigin-3). It was concluded that cell surface basigin functions as a membrane receptor for soluble basigin and this homophilic interaction is not dependent upon glycosylation of the basigin ligand.

This study aimed to characterize the endometrial transcriptome and functional pathways overrepresented in the endometrium of cows treated to ovulate larger (≥ 13 mm) versus smaller (≤ 12 mm) follicles. Nelore cows were pre-synchronized prior to receiving cloprostenol (large follicle; LF) or not (small follicle group; SF), along with a progesterone device on D−10. Devices were withdrawn and cloprostenol administered 42 to 60 hours (LF) or 30 to 36 hours (SF) before GnRH agonist treatment (D0). Tissues were collected on D4 (Exp.1; N = 24) or D7 (Exp.2; N = 60). Endometrial transcriptome was obtained by RNA-seq whereas proliferation and apoptosis were assessed by immunohistochemistry. Overall, LF cows developed larger follicles and CLs, and produced greater amounts of E2 (D-1; Exp.1; SF: 0.7±0.2; LF: 2.4±0.2 pg/mL; Exp.2; SF: 0.5±0.1; LF: 2.3±0.6 pg/mL) and P4 (D4; Exp.1; SF: 0.8±0.1; LF: 1.4±0.2 ng/mL; D7; Exp.2; SF: 2.5±0.4; LF: 3.7±0.4 ng/mL). Functional enrichment indicated that biosynthetic and metabolic processes were enriched in LF endometrium, whereas SF endometrium transcriptome was biased towards cell proliferation. Data also suggested reorganization of the extracellular matrix (ECM) towards a proliferation permissive phenotype in SF endometrium. LF endometrium showed an earlier onset of proliferative activity, whereas SF endometrium expressed a delayed increase in glandular epithelium proliferation. In conclusion, the periovulatory endocrine milieu regulates bovine endometrial transcriptome and seems to determine the transition from a proliferation permissive to a biosynthetic and metabolically active endometrial phenotype, which may be associated with the preparation of an optimally receptive uterine environment.

In cattle, the oviduct is a tubular organ that connects the ovary and the uterus. The oviduct lumen stages a dynamic set of cellular and molecular interactions to fulfill the noble role of generating a new individual. Specific anatomical niches along the oviduct lumen provide the appropriate microenvironment for final sperm capacitation, oocyte capture and fertilization, and early embryo development and transport. To accomplish such complex tasks, the oviduct undergoes spatially and temporally-regulated morphological, biochemical, and physiological changes that are associated with endocrine events of the estrous cycle. Specifically, elevated periovulatory concentrations of estradiol (E2) and progesterone (P4) influence gene expression and morphological changes that have been associated positively to fertility in beef cattle. In this review, we explore how E2 and P4 influence oviductal function in the beginning of the estrous cycle, and prepare the oviductal lumen for interactions with gametes and embryos.