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The history and current status of anti-sperm antibody research
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Abstracts for the 29th Annual Congress of Japanese Society / Journal of Reproductive Immunology 106 (2014) 1–20
we have studied the implication of bone morphogenetic proteins (BMP) in the ovarian physiology. In the present study, we exhibit our data regarding (1) folliculogenesis, (2) ovulation and (3) polycystic ovary syndrome (PCOS), especially from the point of the relationship between ovarian cells and immune-competent cells. Folliculogenesis: Although the formation of an individual capillary network in the theca cell layer is required for ovarian folliculogenesis, the mechanism has not been clarified. We found that theca cell derived BMP-7 stimulated VEGF secretion levels in GC significantly. In endothelial cells, BMP-7 increased the cell number and induced VEGF receptor mRNA. BMP-7 might work to form vasculature around follicles via induction of VEGF expression in GC and increased sensitivity of endothelial cells to VEGF. Ovulation: As granulocyte colony-stimulating factor (G-CSF) is known to be a candidate for a treatment of luteinized unruptured follicle (LUF), neutrophils might be involved in ovulatory process. BMP cytokine is known to regulate ovulation, as BMP-6 null mice exhibit a decrease in the number of ovulatory follicles without effect on either the morphology or the dynamics of follicular development. We found that BMP-6 significantly increased growthregulated oncogene (GRO)-␣ levels in human GC. On the other hand, BMP-6 suppressed the relative expression of the protease inhibitors, secretory leukocyte peptidase inhibitor (SLPI) in GC. BMP-6 might play a role in ovulation by increasing the accumulation of neutrophils in the ovulatory follicle and suppressing the effect of protease inhibitor. PCOS: Plasminogen activator inhibitor-1 (PAI-1), the main physiological inhibitor of plasminogen activation, is elevated in women with PCOS and has been linked to PCOS in a mouse model of the disease. We have found that TGF- and TNF-␣ which are involved in the etiology of PCOS, increased PAI-1 secretion levels by cultured GC. Insulin sensitizing drugs suppressed TGF- and TNF␣ mRNA expression in peritoneal fluid mononuclear cells. Our data suggested that insulin sensitizing agents may provide a potential therapy for PCOS via down regulation of PAI-1 expression indirectly. To understand the etiology of PCOS, the regulation of immune-competent cells should be taken into consideration. http://dx.doi.org/10.1016/j.jri.2014.09.008 The history and current status of anti-sperm antibody research A. Hasegawa ∗ , H. Shibahara Department of Obstetrics and Gynecology, Center of Reproductive Medicine in Hyogo College of Medicine, Japan It was at the end of the 19th century that research concerning sperm immunity began. Since Landsteiner’s reported that boar sperm was impaired in abdominal cavity of guinea-pigs after successive intraperitoneal injections (Centbl. f. Bakreriol. 25, 546, 1899), a number of studies examined toxic effects on sperm. The period was coincident
with the time when Ehrlich proposed “side-chain theory”, a basis of modern immunology. At that time, researchers’ interest was whether or not anti-sperm antibody (ASA) was produced in same species followed by sterility in females In humans, it was reported that volunteer women immunized with heat-treated sperm produced ASA which resulted in sterility, although this result was questionable (Baskin, J Contracept. 1, 15, 1935). Clear evidence was provided by Isojima by the immunization of testis homogenate with Freund’s adjuvant to guinea-pigs (Science, 129, 44, 1958). After that, the identification and isolation of spermspecific antigens were intensively studied. From 1980 to 2000, the monoclonal antibody technology revealed antigenic epitopes and they were applied to immunological contraception. The major molecules for current advanced research like IZOMO, ADAM family, Eppin, SP10, SPA family and CD52 have been identified in this period using rabbits, guinea-pigs, mice, pigs and humans. In clinical aspects, such as unexplained infertility in women, ASA has been frequently detected in the sera since the 1960s. However, ASA does not always evoke infertility. Although ASA was detected by ELISA, immuno-fluorescence, and western blot assays in women, most cases have normal fertility. Heterogeneity of antigens recognized by ASA means many problems remain unsolved. One method (Sperm Immobilization Test: SIT) that detects sperm motility impairment is recommended as a feasible assay for detection of ASA, because inhibition of sperm motility is directly correlated to sperm functions. In physiological conditions, complement activity is negatively regulated in female reproductive tracts via CD55, CD59, etc. We will discuss the relationship between sperm impairment by ASA and complement regulation systems. http://dx.doi.org/10.1016/j.jri.2014.09.009
Oral free communication abstracts Onionin A inhibits epithelial ovarian cancer proliferation by the suppression of STAT3 activation in tumor cells and macrophages J. Nakao 1,2,∗ , Y. Fujiwara 2 , K. Takaishi 1 , Y. Komohara 2 , H. Tashiro 1 , M. Takeya 2 , H. Katabuchi 1 1 Department of Obstetrics and Gynecology, Kumamoto University, Japan 2 Department of Cell Pathology, Faculty of Life Sciences, Kumamoto University, Japan
Objective: In epithelial ovarian cancer (EOC), M2 macrophage (Mø), which is one of components forming the cancer microenvironment, is polarized from Mø and plays an important role in cancer cell proliferation via STAT3 pathway. Onionin A (ONA), a natural compound derived from onion, has an inhibitory effect on M2 polarization by STAT3 inactivation. Here we elucidated effects of ONA in EOC via STAT3 inactivation. Methods: Effects of ONA alone and the combinations of ONA and anti-cancer drugs (PTX, CBDCA, CDDP) on
Abstracts for the 29th Annual Congress of Japanese Society / Journal of Reproductive Immunology 106 (2014) 1–20
we have studied the implication of bone morphogenetic proteins (BMP) in the ovarian physiology. In the present study, we exhibit our data regarding (1) folliculogenesis, (2) ovulation and (3) polycystic ovary syndrome (PCOS), especially from the point of the relationship between ovarian cells and immune-competent cells. Folliculogenesis: Although the formation of an individual capillary network in the theca cell layer is required for ovarian folliculogenesis, the mechanism has not been clarified. We found that theca cell derived BMP-7 stimulated VEGF secretion levels in GC significantly. In endothelial cells, BMP-7 increased the cell number and induced VEGF receptor mRNA. BMP-7 might work to form vasculature around follicles via induction of VEGF expression in GC and increased sensitivity of endothelial cells to VEGF. Ovulation: As granulocyte colony-stimulating factor (G-CSF) is known to be a candidate for a treatment of luteinized unruptured follicle (LUF), neutrophils might be involved in ovulatory process. BMP cytokine is known to regulate ovulation, as BMP-6 null mice exhibit a decrease in the number of ovulatory follicles without effect on either the morphology or the dynamics of follicular development. We found that BMP-6 significantly increased growthregulated oncogene (GRO)-␣ levels in human GC. On the other hand, BMP-6 suppressed the relative expression of the protease inhibitors, secretory leukocyte peptidase inhibitor (SLPI) in GC. BMP-6 might play a role in ovulation by increasing the accumulation of neutrophils in the ovulatory follicle and suppressing the effect of protease inhibitor. PCOS: Plasminogen activator inhibitor-1 (PAI-1), the main physiological inhibitor of plasminogen activation, is elevated in women with PCOS and has been linked to PCOS in a mouse model of the disease. We have found that TGF- and TNF-␣ which are involved in the etiology of PCOS, increased PAI-1 secretion levels by cultured GC. Insulin sensitizing drugs suppressed TGF- and TNF␣ mRNA expression in peritoneal fluid mononuclear cells. Our data suggested that insulin sensitizing agents may provide a potential therapy for PCOS via down regulation of PAI-1 expression indirectly. To understand the etiology of PCOS, the regulation of immune-competent cells should be taken into consideration. http://dx.doi.org/10.1016/j.jri.2014.09.008 The history and current status of anti-sperm antibody research A. Hasegawa ∗ , H. Shibahara Department of Obstetrics and Gynecology, Center of Reproductive Medicine in Hyogo College of Medicine, Japan It was at the end of the 19th century that research concerning sperm immunity began. Since Landsteiner’s reported that boar sperm was impaired in abdominal cavity of guinea-pigs after successive intraperitoneal injections (Centbl. f. Bakreriol. 25, 546, 1899), a number of studies examined toxic effects on sperm. The period was coincident
with the time when Ehrlich proposed “side-chain theory”, a basis of modern immunology. At that time, researchers’ interest was whether or not anti-sperm antibody (ASA) was produced in same species followed by sterility in females In humans, it was reported that volunteer women immunized with heat-treated sperm produced ASA which resulted in sterility, although this result was questionable (Baskin, J Contracept. 1, 15, 1935). Clear evidence was provided by Isojima by the immunization of testis homogenate with Freund’s adjuvant to guinea-pigs (Science, 129, 44, 1958). After that, the identification and isolation of spermspecific antigens were intensively studied. From 1980 to 2000, the monoclonal antibody technology revealed antigenic epitopes and they were applied to immunological contraception. The major molecules for current advanced research like IZOMO, ADAM family, Eppin, SP10, SPA family and CD52 have been identified in this period using rabbits, guinea-pigs, mice, pigs and humans. In clinical aspects, such as unexplained infertility in women, ASA has been frequently detected in the sera since the 1960s. However, ASA does not always evoke infertility. Although ASA was detected by ELISA, immuno-fluorescence, and western blot assays in women, most cases have normal fertility. Heterogeneity of antigens recognized by ASA means many problems remain unsolved. One method (Sperm Immobilization Test: SIT) that detects sperm motility impairment is recommended as a feasible assay for detection of ASA, because inhibition of sperm motility is directly correlated to sperm functions. In physiological conditions, complement activity is negatively regulated in female reproductive tracts via CD55, CD59, etc. We will discuss the relationship between sperm impairment by ASA and complement regulation systems. http://dx.doi.org/10.1016/j.jri.2014.09.009
Oral free communication abstracts Onionin A inhibits epithelial ovarian cancer proliferation by the suppression of STAT3 activation in tumor cells and macrophages J. Nakao 1,2,∗ , Y. Fujiwara 2 , K. Takaishi 1 , Y. Komohara 2 , H. Tashiro 1 , M. Takeya 2 , H. Katabuchi 1 1 Department of Obstetrics and Gynecology, Kumamoto University, Japan 2 Department of Cell Pathology, Faculty of Life Sciences, Kumamoto University, Japan
Objective: In epithelial ovarian cancer (EOC), M2 macrophage (Mø), which is one of components forming the cancer microenvironment, is polarized from Mø and plays an important role in cancer cell proliferation via STAT3 pathway. Onionin A (ONA), a natural compound derived from onion, has an inhibitory effect on M2 polarization by STAT3 inactivation. Here we elucidated effects of ONA in EOC via STAT3 inactivation. Methods: Effects of ONA alone and the combinations of ONA and anti-cancer drugs (PTX, CBDCA, CDDP) on