The Role Of Caspase-1 And IL-1β Protein Expressions In CHM Arising From Different Heredity Background

BackgroundHydatidiform mole is an aberrant human pegnancy with no embryo, it is characterized by stromal oedema with formation of cisternal, diffuse trophoblastic hyperplasia .Its incidence rate varied from in different races and regions, the incidence rate is about 0. 78 per 1000 pregnancy in china and is from 1/2000 to 1/1000 pregnancy in the Unite States and to 1/125 in southeast Asia .The exact etiology of HM still remains unclear , the predisposoing factors which are known to influence HM are:menarche, parity, age at first pregnancy, genetic disturbances, malnutrition,viral infection, social-economic status and Asian descent. HM can be classified in CHM(Complete hydatidiform moles, CHM) and PHM (Partial hydatidiform moles, PHM) according to histopathology. Most PHM is diandric triploid and are formed by dispermic fertilization of a haploid oocyte , but also can be formed by a diploid sperm fertilizated with an eggin some occasions. CHM often have diploid genome, its diploid genome can come from its paternal , is called AnCHM (Androgenetic complete hydatidiform moles, AnCHM) ;and can come from its paternal and maternal, is called BiCHM. About 75-80% of AnCHM have a 46 XX karyotype, resulting from monospermic(23 X) fertilization of an oocyte with inactivated genome with duplication of the male haploid genome contributed by the fertilizating sperm. About 20-25% of AnCHM result from dispermic fertilization of an oocyte with an inactivating genome, its karyotype is 46 XY. BiCHM(Biparental complete hydatidiform moles, BiCHM) is a speciall type of CHM, and about 20% of its, which always is correlate with familial recurrent hydatidiform mole . In these family two or more two member were affected with recurrent hydatidiform mole . It suggests that BiCHM should be an autosomal recessive heredity disease from fact which members of the affected family were prone to affect HM, and we can presume that the affected women maybe have some heredity defection in ovarian function according that the fact that the affected women still have HM with different partners. BiCHM is rare , and it was proved in some sporadic recurrent HM except familial HM in recent year, which maybe represent different individual whith same causativefactor. BiCHM which have partenal and maternal haploid genome has the same histopathological and clinical characteristic as AnCHM even if arising from different heredity background , and can not differentiate each other ,moreover the affected women that had BiCHM have no good outcome of pregnancy , and hardly a normal pregnancy in all her life , either abortion and stillbirth or HM, the etiology of its is unknown yet. The alternative therapy:is to consider receiving donor eggs followed IVF(in-vitro fertilization) to avoid BiCHM, but PHM or AnCHM can be prevented through considering ICSI (intracytoplasma sperm cytoplasma injection) followed PGD (prcimplantation genetic diagnosis). AnCHM is identical to BiCHM in clinic and histopathology, the method of DNA analysis is very important means that it was used to differentiate BiCHM from AnCHM , but can not be a routine detected means because of its expensive and inconvenience and wasting time and strenuosity. The single base mutation in one locus of NALP7 gene was found in four FRMs and a sporadic recurrent mole in recent research, which was not found in control group which consists of 200 normal women. To postulate that mutation of NALP7 gene is a candidated cause factor of BiCHM, which can be appear in which NALP7 gene inhibits process of pro-caspase-1 and pro-IL-1β , Caspase-1 also named Interleukin -1β converting enzyme, consisting of 404-amino acid residues , about 45kDa . Caspase-1 is one of 14 Caspase proteins . It is correlate with apoptosis of eukaryotic cell and cytokine maturation , but also participate in growth and differentiation of cell as well as barring infection . Caspase-1 protein usually locates in cytoplasma with zymogen manners , and bring into play through activing itself. IL-1β was named lymphocytical active cytokine, its secretion and production can be produced and processed by many types of cell. It always is in cytoplasma with Pro - IL-1β manners , pro- IL-1β can be developed into mature IL 1β after Caspase-1 catalysis and be secreted into extracellular space following .It is a pleiotropic cytokine that activates a number of immunological and inflammatory pathways , and abundant in the uterine milieu during the peri implantation period , which facilitate the implantation of the blastocyst , regulates the protease network and controls the extent to which the trophoblast may invade the maternal endometrium ,clears the toxicity effections which was developed by lipopolysaccharide or peptidoglycan of gram-negative bacteria that known to cause fetal loss in human .prevent HM from developing. Mutation of NALP7 causeupregulation of NALP7 protein , which inhibits processing of pro-Caspase-land pro-IL-1β through contacting with some mediates proteins, and cause HM being. Because the commercial antibody of NALP7 is not developed yet at present, and study on the role of caspase-1 and IL—1β protein expressions in CHM arising from different heredity background do not appear in literatures at the same time. we try to explore the role of caspase-1 and IL-1β protein expressions in CHM arising from different heredity background, hope to find out a simple and effective routine means which can differentiate BiCHM from AnCHM. ObjectiveApply the technology of DNA analysis to differentiate AnCHM from BiCHM in CHM , following to detect the expression of Caspase-1 and IL—1β protein in AnCHM and BiCHM and explore whether it is in concordance with DNA analysis of CHM, hope to find out a simple and effective biomarker which can differentiate BiCHM from AnCHM. It avails to clinic diagnosis and reveal the etiology of BiCHM . Materials and methods50 cases of CHM which were firstly evacuated and were diagnosised by histopathology which was from inpatient ofwomen' s hospital school of medicine Zheijiang university during 2004.01—2006.11 and Shao xing second hospital Zheijiang province during 2005.11 — 2006.11. To extract respectively 10ml peripherad blood of the couples, to apply 9 locus of polymorphisms of microsatellate to detect the parental origin of CHM , then AnCHMs are designated to group A , BiCHMs are group B according to the result , 39 cases of normal chorionic villus are designated to control group. To detect the expression of Caspase-1 and IL-1β protein in the three groups. Result 1.43 cases of AnCHMs were found among 50 cases of CHM throughDNA analysis, about 86%;7 BiCHMs were found, about 14%;and noPHMs were found 2. The expression of caspase-1 and IL-1β in the three groups tissue are not significance difference via comparision between every two groups (P > 0.05).3. The expression of caspase-1 and IL—1β in CHM were not concordance with DNA analysis at all (P=0. 000), but correlation between caspase-1 and IL-1β which was proved (Pearson parameter=1.000, P=0. 019).ConclusionsThe expression of caspase-1 and IL—1β in CHM were not concordance with DNA analysis at all(P=0. 000). The results suggest that their expression in CHM , Which can not be a biomarker to differentiate BiCHM from AnCHM, Both are not the candidated factors of BiCHM .