ADAMTS Proteases: Importance in Animal Reproduction

Abstract

Many reproductive physiological processes, such as folliculogenesis, ovulation, implantation, and fertilization, require the synthesis, remodeling, and degradation of the extracellular matrix (ECM). The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) family genes code for key metalloproteinases in the remodeling process of different ECM. Several genes of this family encode for proteins with important functions in reproductive processes; in particular, ADAMTS1, 4, 5 and 9 are genes that are differentially expressed in cell types and the physiological stages of reproductive tissues. ADAMTS enzymes degrade proteoglycans in the ECM of the follicles so that the oocytes can be released and regulate follicle development during folliculogenesis, favoring the action of essential growth factors, such as FGF-2, FGF-7 and GDF-9. The transcriptional regulation of ADAMTS1 and 9 in preovulatory follicles occurs because of the gonadotropin surge in preovulatory follicles, via the progesterone/progesterone receptor complex. In addition, in the case of ADAMTS1, pathways involving protein kinase A (PKA), extracellular signal regulated protein kinase (ERK1/2) and the epidermal growth factor receptor (EGFR) might contribute to ECM regulation. Different Omic studies indicate the importance of genes of the ADAMTS family from a reproductive aspect. ADAMTS genes could serve as biomarkers for genetic improvement and contribute to enhance fertility and animal reproduction; however, more research related to these genes, the synthesis of proteins encoded by these genes, and regulation in farm animals is needed.

Comparison of Steroidogenic and Ovulation-Inducing Effects of Orthosteric and Allosteric Agonists of Luteinizing Hormone/Chorionic Gonadotropin Receptor in Immature Female Rats

“…The stimulating effects of TP4/2 and hCG on Adamts-1 expression and the content of ADAMTS-1 in the ovary were comparable, indicating the similarity of their regulatory influence on the production of this metalloproteinase, which is responsible for the dissolution of the connective tissue of the follicle. There is evidence that the level of expression of the Adamts-1 gene is positively correlated with the production of progesterone, as the main inducer of the expression of this gene [86,92], and this correlates well with our data on a consistent increase in the level of progesterone in the blood and the expression of the Adamts-1 gene in the ovaries of rats (Tables 3 and 6). Of importance in this case is the increase in the expression of progesterone receptors in granulosa cells, which is caused not only by the preovulatory LH peak and gonadotropin preparations with LH activity but also by FSH [92,93].…”

“…Matrix metalloproteinase with thrombospondin type 1 motifs-1 (ADAMTS-1) in the ovaries is localized in the cumulus-oocyte complex and carries out the degradation of large-sized aggregating proteoglycans, including versican, which is necessary for the reorganization of the extracellular matrix and the normal course of folliculogenesis and ovulation [85,86]. The expression and functional activity of ADAMTS-1 in cumulus cells are closely related to the ability of the oocyte to fertilize [35], and a decrease in the expression of this metalloproteinase is associated with impaired maturation and quality of oocytes in women with polycystic ovary syndrome [86][87][88][89]. Expression of the gene encoding ADAMTS-1 begins several hours after administration of LH or hCG, as a response to gonadotropin-induced increases in the level of proinflammatory factors, and was elevated until ovulation, after which it decreased during the CL formation [90,91].…”