Recurrent pregnancy loss （RPL） is a condition with complex etiologies, to which both genetic and envi- ronmental factors may contribute. During the last decade, studies indicated that the expression patterns of the ...Recurrent pregnancy loss （RPL） is a condition with complex etiologies, to which both genetic and envi- ronmental factors may contribute. During the last decade, studies indicated that the expression patterns of the pro- kineticin receptor （PKR1 and PKR2） are closely related to early pregnancy. However, there are few studies on the role of PKR1 and PKR2 in RPL. In this study, we purpose to investigate the association between polymorphisms of the prokineticin receptor （PKR1 rs4627609 and PKR2 rs6053283） and RPL on a group of 93 RPL cases and 169 healthy controls. Genotyping of the single nucleotide polymorphisms （SNPs） was performed using a Sequenom MassARRAY iPLEX system. The results revealed a significant association between PKR2 rs6053283 polymorphism and RPL （P=0.003）, whereas no association was observed between PKR1 rs4627609 polymorphism and RPL （P=-0.929） in the Chinese Han population.展开更多
Varicocele is one of the most important causes of male infertility,as this condition leads to a decline in sperm quality.It is generally believed that the presence of varicocele induces an increase in reactive oxygen ...Varicocele is one of the most important causes of male infertility,as this condition leads to a decline in sperm quality.It is generally believed that the presence of varicocele induces an increase in reactive oxygen species levels,leading to oxidative stress and sperm apoptosis;however,the specific pathogenic mechanisms affecting spermatogenesis remain elusive.Prokineticin 2(PK2),a secretory protein,is associated with multiple biological processes,including cell migration,proliferation,and apoptosis.In the testis,PK2 is expressed in spermatocytes under normal physiological conditions.To investigate the role of PK2 in varicocele,a rat varicocele model was established to locate and quantify the expression of PK2 and its receptor,prokineticin receptor 1(PKR1),by immunohistochemistry and quantitative real-time PCR assays(qPCR).Moreover,H2O2 was applied to mimic the oxidative stress state of varicocele through coculturing with a spermatocyte-derived cell line(GC-2)in vitro,and the apoptosis rate was detected by flow cytometry.Here,we illustrated that the expression levels of PK2 and PKR1 were upregulated in the spermatocytes of the rat model.Administration of H202 stimulated the overexpression of PK2 in GC-2.Transfection of recombinant pCMV-HA-PK2 into GC-2 cells promoted apoptosis by upregulating cleaved-caspase-3,caspase-8,and B cell lymphoma 2-associated X;downregulating B cell lymphoma 2;and promoting the accumulation of intracellular calcium.Overall,we revealed that the varicocele-induced oxidative stress stimulated the overexpression of PK2,leading to apoptosis of spermatocytes.Our study provides new insight into the mechanisms underlying oxidative stress-associated male infertility and suggests a novel therapeutic target for male infertility.展开更多
Objective: Prokineticin-1 (PROK1) is a recently described protein with a wide range of functions including tissue specific angiogenesis, modulation of inflammatory responses and regulation of haematopoiesis. PROK1 has...Objective: Prokineticin-1 (PROK1) is a recently described protein with a wide range of functions including tissue specific angiogenesis, modulation of inflammatory responses and regulation of haematopoiesis. PROK1 has been found in the steroidogenic organs like ovary, testis, adrenal and specially placenta and they have been found to have a role in development of the olfactory system and GnRH system. The aim was to update the role of PROK1 and PROK2 inhuman reproduction since the review was provided by Maldono-Perez (2007) on the potentials of prokineticins in reproduction. Design: A review of international scientific literature by a search of Pubmed and the authors files was done for citation of articles relevant to prokineticins in reproduction, be it its role in ovary, testis, uterus with special emphasis on implantation, normal pregnancy, in labour, pathophysiological states like tubal pregnancy, pcos, various genital tumours, and cases of isolated hypogonadotropic hypogonadism with mutations with PROK2/ PROKR2 and studies detailing functional mechanisms. Results: In the normal cycle, PROK1 has been found to have important roles in implantation, regulating several genes like COX-2, IL-8, IL-11, CTGF related to implantation. Initially murine studies revealed a critical role of PROK2 pathway on olfactory bulb morphogenesis and GnRH secretion which was accidentally discovered and since then several studies on mutations in PROK2/PROKR2 showed that they underlie some case of KS in humans. Although in mouse heterozygote state is not associated with clinical phenotype, most of human mutations are heterozygous. Conclusions: Role of PROK-1 in the process of implantation, with a deeper understanding of the process success rates in IVF and ART can be improved, besides understanding the pathophysiology of tubal pregnancy. Further presence in ovarian follicles of PROK1 can be used to plan a strategy for treating pcos. Development of antagonism of PROK’S may be a helpful strategy in treating preterm labour.展开更多
AIM： TO study the implication of prokineticin 1 （PKI/EGVEGF） and prokineticin 2 （PK2/13v8） in hepatocellular carcinoma angiogenesis.METHODS： The gene induction of PK1/EG-VEGF and PK2/Bv8 was investigated in 10 n...AIM： TO study the implication of prokineticin 1 （PKI/EGVEGF） and prokineticin 2 （PK2/13v8） in hepatocellular carcinoma angiogenesis.METHODS： The gene induction of PK1/EG-VEGF and PK2/Bv8 was investigated in 10 normal, 28 fibrotic and 28 tumoral livers by using real time PCR. Their expression was compared to the expression of VEGF （an angiogenesis marker）, vWF （an endothelial cell marker） and to CD68 （a monocyte/macrophage marker）. Furthermore, the rnRNA levels of PK1/EG-VEGF, PK2/Bv8, prokineticin receptor 1 and 2 were evaluated by real time PCR in isolated liver cell populations. Finally, PK2/Bv8 protein was detected in normal liver paraffin sections and in isolated liver cells by immunohistochernistry and immunocytochemistry.RESULTS： PK2/Bv8 mRNA but not PK1/EG-VEGF was expressed in all types of normal liver samples examined. In the context of liver tumor development, we reported that PK2/13v8 correlates only with CD68 and showed a significant decrease in expression as the pathology evolves towards cancer. Whereas, VEGF and vWF mRNA were significantly upregulated in both fibrosis and HCC,as expected. In addition, out of all isolated liver cells examined, only Kupffer cells （liver resident macrophages） express significant levels of PK2/Bv8 and its receptors, prokineticin receptor 1 and 2.CONCLUSION： In normal liver PK2/Bv8 and its receptors were specifically expressed by Kupffer cells. PK2/Bv8 expression decreased as the liver evolves towards cancer and did not correlate with HCC angiogenesis.展开更多
基金Project supported by the National Natural Science Foundation of China(No.81571503)
文摘Recurrent pregnancy loss （RPL） is a condition with complex etiologies, to which both genetic and envi- ronmental factors may contribute. During the last decade, studies indicated that the expression patterns of the pro- kineticin receptor （PKR1 and PKR2） are closely related to early pregnancy. However, there are few studies on the role of PKR1 and PKR2 in RPL. In this study, we purpose to investigate the association between polymorphisms of the prokineticin receptor （PKR1 rs4627609 and PKR2 rs6053283） and RPL on a group of 93 RPL cases and 169 healthy controls. Genotyping of the single nucleotide polymorphisms （SNPs） was performed using a Sequenom MassARRAY iPLEX system. The results revealed a significant association between PKR2 rs6053283 polymorphism and RPL （P=0.003）, whereas no association was observed between PKR1 rs4627609 polymorphism and RPL （P=-0.929） in the Chinese Han population.
基金the National Natural Science Foundation of China(Grant No.81871148,No.81701539 and No.81571496).
文摘Varicocele is one of the most important causes of male infertility,as this condition leads to a decline in sperm quality.It is generally believed that the presence of varicocele induces an increase in reactive oxygen species levels,leading to oxidative stress and sperm apoptosis;however,the specific pathogenic mechanisms affecting spermatogenesis remain elusive.Prokineticin 2(PK2),a secretory protein,is associated with multiple biological processes,including cell migration,proliferation,and apoptosis.In the testis,PK2 is expressed in spermatocytes under normal physiological conditions.To investigate the role of PK2 in varicocele,a rat varicocele model was established to locate and quantify the expression of PK2 and its receptor,prokineticin receptor 1(PKR1),by immunohistochemistry and quantitative real-time PCR assays(qPCR).Moreover,H2O2 was applied to mimic the oxidative stress state of varicocele through coculturing with a spermatocyte-derived cell line(GC-2)in vitro,and the apoptosis rate was detected by flow cytometry.Here,we illustrated that the expression levels of PK2 and PKR1 were upregulated in the spermatocytes of the rat model.Administration of H202 stimulated the overexpression of PK2 in GC-2.Transfection of recombinant pCMV-HA-PK2 into GC-2 cells promoted apoptosis by upregulating cleaved-caspase-3,caspase-8,and B cell lymphoma 2-associated X;downregulating B cell lymphoma 2;and promoting the accumulation of intracellular calcium.Overall,we revealed that the varicocele-induced oxidative stress stimulated the overexpression of PK2,leading to apoptosis of spermatocytes.Our study provides new insight into the mechanisms underlying oxidative stress-associated male infertility and suggests a novel therapeutic target for male infertility.
文摘Objective: Prokineticin-1 (PROK1) is a recently described protein with a wide range of functions including tissue specific angiogenesis, modulation of inflammatory responses and regulation of haematopoiesis. PROK1 has been found in the steroidogenic organs like ovary, testis, adrenal and specially placenta and they have been found to have a role in development of the olfactory system and GnRH system. The aim was to update the role of PROK1 and PROK2 inhuman reproduction since the review was provided by Maldono-Perez (2007) on the potentials of prokineticins in reproduction. Design: A review of international scientific literature by a search of Pubmed and the authors files was done for citation of articles relevant to prokineticins in reproduction, be it its role in ovary, testis, uterus with special emphasis on implantation, normal pregnancy, in labour, pathophysiological states like tubal pregnancy, pcos, various genital tumours, and cases of isolated hypogonadotropic hypogonadism with mutations with PROK2/ PROKR2 and studies detailing functional mechanisms. Results: In the normal cycle, PROK1 has been found to have important roles in implantation, regulating several genes like COX-2, IL-8, IL-11, CTGF related to implantation. Initially murine studies revealed a critical role of PROK2 pathway on olfactory bulb morphogenesis and GnRH secretion which was accidentally discovered and since then several studies on mutations in PROK2/PROKR2 showed that they underlie some case of KS in humans. Although in mouse heterozygote state is not associated with clinical phenotype, most of human mutations are heterozygous. Conclusions: Role of PROK-1 in the process of implantation, with a deeper understanding of the process success rates in IVF and ART can be improved, besides understanding the pathophysiology of tubal pregnancy. Further presence in ovarian follicles of PROK1 can be used to plan a strategy for treating pcos. Development of antagonism of PROK’S may be a helpful strategy in treating preterm labour.
基金INSERM,the Ministère de l'Education Nationale de la Recherche et de la Technologie,the Région Bretagne.No.2079
文摘AIM： TO study the implication of prokineticin 1 （PKI/EGVEGF） and prokineticin 2 （PK2/13v8） in hepatocellular carcinoma angiogenesis.METHODS： The gene induction of PK1/EG-VEGF and PK2/Bv8 was investigated in 10 normal, 28 fibrotic and 28 tumoral livers by using real time PCR. Their expression was compared to the expression of VEGF （an angiogenesis marker）, vWF （an endothelial cell marker） and to CD68 （a monocyte/macrophage marker）. Furthermore, the rnRNA levels of PK1/EG-VEGF, PK2/Bv8, prokineticin receptor 1 and 2 were evaluated by real time PCR in isolated liver cell populations. Finally, PK2/Bv8 protein was detected in normal liver paraffin sections and in isolated liver cells by immunohistochernistry and immunocytochemistry.RESULTS： PK2/Bv8 mRNA but not PK1/EG-VEGF was expressed in all types of normal liver samples examined. In the context of liver tumor development, we reported that PK2/13v8 correlates only with CD68 and showed a significant decrease in expression as the pathology evolves towards cancer. Whereas, VEGF and vWF mRNA were significantly upregulated in both fibrosis and HCC,as expected. In addition, out of all isolated liver cells examined, only Kupffer cells （liver resident macrophages） express significant levels of PK2/Bv8 and its receptors, prokineticin receptor 1 and 2.CONCLUSION： In normal liver PK2/Bv8 and its receptors were specifically expressed by Kupffer cells. PK2/Bv8 expression decreased as the liver evolves towards cancer and did not correlate with HCC angiogenesis.
