Bone morphogenetic protein-1/Tolloid is the prototype of a family of metalloproteases implicated in
embryonic patterning in diverse species. Members of this family contain an astacin-like protease domain
and varying numbers of CUB protein-protein interaction domains and EGF motifs.
NCBI Summary:
This gene encodes a protein that is capable of inducing formation of cartilage in vivo. Although other bone morphogenetic proteins are members of the TGF-beta superfamily, this gene encodes a protein that is not closely related to other known growth factors. This gene is expressed as alternatively spliced variants that share an N-terminal protease domain but differ in their C-terminal region. [provided by RefSeq, Aug 2008]
Bone morphogenetic protein 1 is expressed in porcine ovarian follicles and promotes oocyte maturation and early embryonic development. Lei X et al. (2016) In the present study, we tried to determine whether bone morphogenetic protein 1 (BMP1) plays a role in ovarian follicular development and early embryo development. We systematically investigated the expression and influence of BMP1 during porcine follicle and early embryonic development. Immunohistochemistry demonstrated that the BMP1 protein is expressed in granular cells and oocytes during follicular development, from primary to pre-ovulatory follicles, including atretic follicles and the corpus luteum. The mRNA expression of BMP1 significantly increased as the porcine follicles grew. Immunofluorescence analysis indicated that BMP1 was expressed in cumulus-oocyte complexes (COCs), oocytes and porcine embryos during early in vitro culture. qPCR and western blot analysis showed that the expression of BMP1 was significantly up-regulated in mature porcine oocytes and COCs compared to immature oocytes and COCs. BMP1 is expressed in early porcine embryos, and its expression reaches a peak at the 8-cell stage. To determine the effect of BMP1 on the maturation of oocytes and the development of early embryos, various concentrations of BMP1 recombinant protein or antibody were added to the in vitro culture media respectively. BMP1 significantly affected the porcine oocyte maturation rate, the cleavage rate and the blastocyst development rate of embryos cultured in vitro in a positive way, as well as the blastocyst cell number. In conclusion, BMP1 is expressed throughout porcine ovarian follicle development and early embryogenesis, and it promotes oocyte maturation and the developmental ability of embryos during early in vitro culture.//////////////////
BMP-1 participates in the selection and dominance of buffalo follicles by regulating the proliferation and apoptosis of granulosa cells. Lei X et al. (2016) BMP1/TLD-related metalloproteinases play a key role in morphogenesis via the proteolytic maturation of a number of extracellular matrix proteins and the activation of a subset of growth factors of the transforming growth factor beta superfamily. Recent data indicated that BMP1 is expressed in sheep ovarian follicles and showed a protease activity. The aim of the present study was to characterize the function of the buffalo BMP1 gene in folliculogenesis. A 3195-bp buffalo BMP1 mRNA fragment was firstly cloned and sequenced, which contained a whole 2967-bp codon sequence. The multialigned results suggested that BMP1 is highly conserved among different species both at the nucleic acid and the amino acid level. BMP1 is located in the oogonium of the fetal buffalo ovary and in the granulosa cells (GCs) and the oocytes of adult ovary from the primordial to the large antral follicles. Further study showed that BMP1 promoted cell cycle and proliferation and inhibited apoptosis in IVC GCs. Adding BMP1 recombinant protein to the culture medium of the GCs increased the expression of the key cell cycle regulators such as cyclin D1 and cyclin D2 and downregulated the expression of cell apoptosis pathway genes such as Cytochrome C, Fas, FasL, and Chop, both at the mRNA and at the protein levels. It also upregulated the expression of PAPP-A, IGF system, and VEGF, and so forth, which play important roles in the selection and dominance of growth follicles. The opposite results were observed by adding BMP1 antibody to the investigation groups. This study suggests that BMP1 regulates the proliferation and apoptosis of IVC GCs by changing the expression pattern of related genes and may potentially promote the selection and dominance of the buffalo follicles.//////////////////
Functions for proteinases in the ovulatory process Ohnishi J, et al .
The ovary is a unique and dynamic organ in respect to rapid and extensive degrees of tissue development and remodeling that are periodically repeated in the female reproductive activity. Ovulation is a directed and sequential process accompanied by broad-spectrum proteolysis and culminates in the follicular rupture to release the matured oocyte. This review will focus on the potential roles of six representative proteinases that are involved in various aspects of ovulatory processes: matrix metalloproteinases (MMPs), plasminogen activator (PA)/plasmin, a disintegrin and metalloproteinase domain with thrombospondin motif (ADAMTS), cathepsin-L, pregnancy-associated plasma protein-A (PAPP-A), and bone morphogenetic protein 1/mammalian Tolloid (BMP-1/mTld). Based on the studies of expression and function, these selected proteinases provide and share diverse functions ranging from cleaving components of the extracellular matrix (ECM) to modulating non-ECM molecules, such as various growth factors and their binding proteins. Consistently, the genetic deletion of each individual gene in mice shows their functional overlap in the reproductive activity.
Expression regulated by
Comment
Ovarian localization
Oocyte, Granulosa
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Maternal gene transcription in mouse oocytes: genes implicated in oocyte maturation and fertilization. Cui XS et al. Maternal gene expression is an important biological process in oocyte maturation and early cleavage. To gain insights into oocyte maturation and early embryo development, we used microarray analysis to compare the gene expression profiles of germinal vesicle (GV)- and metaphase II (MII)-stage oocytes. The differences in spot intensities were normalized and grouped using the Avadis Prophetic software platform. Of the 12164 genes examined, we found 1682 genes with more highly expression in GV-stage oocytes than in MII-stage oocytes, while 1936 genes were more highly expressed in MII-stage oocytes (P<0.05). The genes were grouped on the basis of the Panther classification system according to their involvement in particular biological processes. The genes that were up-regulated in GV oocytes were more likely to be involved in protein metabolism and modification, the mitotic cell cycle, electron transport, or fertilization or belong to the microtubule/cytoskeletal protein family. The genes specifically upregulated in the MII oocytes were more likely to be involved in DNA replication, amino acid metabolism, or expression of G protein-coupled receptors and signaling molecules. Identification of genes that are preferentially expressed at particular oocyte maturation stages provides insights into the complex gene regulatory networks that drive oocyte maturation and fertilization. 5.5. fold higher in MII than GV oocytes.
First Evidence of Bone Morphogenetic Protein 1 Expression and Activity in Sheep Ovarian Follicles. Canty-Laird E et al. Bone morphogenetic protein 1 (BMP1) is a vertebrate metalloproteinase of the astacin family. BMP1 plays a key role in regulating the formation of the extracellular matrix (ECM), particularly by processing the C-propeptide of fibrillar procollagens. BMP1 also promotes BMP signaling by releasing BMP signaling molecules from complexes with the BMP-antagonist chordin. As a result of BMP1's dual role in both ECM formation and BMP signaling, we hypothesized that BMP1 could play a role in ovarian physiology. Using the sheep ovary as a model system, it was shown that BMP1 was expressed in the ovary throughout early fetal stages to adulthood. Furthermore, in adult ovaries, BMP1 was expressed along with chordin, BMP4 and twisted gastrulation, together known to form an extracellular regulatory complex for BMP signaling. Within ovine ovaries, immunohistochemical localization demonstrated that BMP1 was present in granulosa cells at all stages of follicular development, from primordial to large antral follicles and that the levels of BMP1 were not affected by the final follicle selection mechanism. In cultured granulosa cells, BMP1 expression was not affected by gonadotropins, but BMP4 and activin A had opposing effects on the levels of BMP1 mRNA. BMP1 appeared to be secreted into the follicular fluid of antral follicles where it is able to exert procollagen C-proteinase (PCP) and chordinase activities. Interestingly, BMP1 activity in follicular fluid decreased with follicular growth.