Tugsjargal Purevdorj, Moeka Arata, Mari Nii, Shota Yamamoto, Hiroki Noguchi, Asuka Takeda, Hidenori Aoki, Hiroaki Inui, Tomohiro Kagawa, Riyo Kinouchi, Yuri Yamamoto, Kanako Yoshida and Takeshi Iwasa : Porcine Placental Extract Improves the Lipid Profile and Body Weight in a Post-Menopausal Rat Model Without Affecting Reproductive Tissues, Nutrients, Vol.17, No.6, 984, 2025.
Tugsjargal Purevdorj, Moeka Arata, Mari Nii, Shota Yamamoto, Hiroki Noguchi, Asuka Takeda, Hidenori Aoki, Hiroaki Inui, Tomohiro Kagawa, Riyo Kinouchi, Yuri Yamamoto, Kanako Yoshida and Takeshi Iwasa : Porcine Placental Extract Improves the Lipid Profile and Body Weight in a Post-Menopausal Rat Model Without Affecting Reproductive Tissues, Nutrients, Vol.17, No.6, 2025.
(キーワード)
alternative therapy / lipid profile / menopause / ovariectomized rats / placental extract / weight loss
Arata Moeka, Kou Tamura, Hidenori Aoki, Hiroki Noguchi, Asuka Takeda, Saki Minato, Yamamoto Shota, Riyo Kinouchi, Kanako Yoshida, Yuri Yamamoto, Takashi Kaji and Takeshi Iwasa : The effects of testosterone on hypothalamic and serum oxytocin levels are affected by the estrogen milieu in female rats, Nutrients, Vol.16, No.15, 2533, 2024.
Takashi Kaji, Hiroki Noguchi, Kou Tamura, Hidenori Aoki, Atsuko Yoshida, Yuri Yamamoto, Kanako Yoshida and Takeshi Iwasa : Survey on the incidence of multiple pregnancies and neonatal outcomes by fertility treatment in Tokushima Prefecture, Japan, The Journal of Medical Investigation : JMI, Vol.71, No.3.4, 251-253, 2024.
(要約)
A survey on the incidence of multiple pregnancies and neonatal outcomes by assisted reproductive technology (ART) and non-ART fertility treatments was performed in 2011 and 2021. Questionnaires were sent to all institutions with obstetrics and gynecology departments in Tokushima Prefecture, Japan, to collect data on fertility treatments and neonatal outcomes in 2011 and 2021. Non-ART fertility treatments were classified into ovarian stimulation (treatments for cases without ovulation disorder) and ovulation induction (treatments for cases with ovulation disorder). Among all pregnancies, the multiple pregnancy rates in 2011 were 7.7% for ovarian stimulation, 5.5% for ovulation induction, and 8.4% for ART, whereas those in 2021 were 3.8%, 2.3%, and 1.9%, respectively. The rates of triplet pregnancies in 2011 were 0.85% for ovulation induction, 2.4% for ovulation induction, and 1.4% for ART, whereas those in 2021 were 0% for all treatments. The rates of low birth weight, admission to a neonatal intensive care unit, and neonatal death in 2011 were 53.8%, 9.61%, and 9.61%, respectively, whereas those in 2021 were 40.9%, 22.7%, and 0%, respectively. These findings indicate that rates of multiple pregnancies, including higher-order multiple pregnancies, by fertility treatment have decreased over the last 10 years in Tokushima Prefecture. However, some adverse neonatal outcomes have still occurred. J. Med. Invest. 71 : 251-253, August, 2024.
Rie Masaki, Yuri Yamamoto, Kou Tamura, Hidenori Aoki, Hiroki Noguchi, Asuka Takeda, Saki Minato, Risa Tanano, Erika Yamanaka, Takaaki Maeda, Tatsuo Sugimoto, Hikari Sasada, Hiroaki Inui, Tomohiro Kagawa, Atsuko Yoshida, Ayuka Mineda, Riyo Kinouchi, Kanako Yoshida, Takashi Kaji and Takeshi Iwasa : Comparison of endogenous hypothalamic and serum OT levels between young and middle-aged perimenopausal female rats, The Journal of Medical Investigation : JMI, Vol.71, No.3.4, 246-250, 2024.
(要約)
Oxytocin (OT) regulates food intake and body weight, particularly in obese individuals. Decreases in the effects of OT have recently been implicated in metabolic disturbances, and the administration of estradiol (E2) increased serum OT levels. Although weight gain is frequently observed in perimenopausal women, endogenous OT levels remain unclear. Therefore, we herein compared endogenous levels of hypothalamic and serum OT between young and middle-aged perimenopausal female rats and examined the relationship between serum estrogen and leptin levels. Body weight and visceral and subcutaneous fat weights were higher in middle-aged rats. Although no significant differences were observed in serum OT and E2 levels, serum leptin levels and hypothalamic mRNA levels of OT and the OT receptor (OTR) were significantly higher in middle-aged rats than in young rats. Serum OT levels did not correlate with hypothalamic OT mRNA levels or serum E2 levels. E2 maintains serum OT levels in perimenopausal rats, and other factors may elevate hypothalamic OT/OTR mRNA levels. Increases in body and fat weights in perimenopausal rats may be attributed to factors other than OT. Therefore, the administration of OT alone may not be sufficient to prevent metabolic disorders induced by the perimenopausal status. J. Med. Invest. 71 : 246-250, August, 2024.
Riyo Kinouchi, Kanako Yoshida, Takako Kawakita, Toshiyuki Yasui, Takeshi Iwasa and Takeshi Katou : Improvement in Quality of Life after Laparoscopic or Robotic-assisted Sacrocolpopexy with a Single Anterior Mesh in Patients with Pelvic Organ Prolapse: A Retrospective Analysis from a Single Institution, Gynecology and Minimally Invasive Therapy, Vol.13, No.3, 168-173, 2024.
(要約)
Pelvic organ prolapse (POP) is a significant health-care problem for older women. We have treated POP surgically using laparoscopic sacrocolpopexy (LSC) or robotic-assisted sacrocolpopexy (RSC). The original LSC and RSC procedures were done with anterior and posterior meshes; however, the use of the single mesh procedure is increasing because of its simplicity and safety. There have been few reports about the change in quality of life (QOL) using the single mesh procedure. Therefore, the present study aimed to retrospectively evaluate the change in QOL by LSC and RSC using a single anterior mesh for women without posterior compartment prolapse. We performed LSC or RSC using a single anterior mesh in 52 patients who had POP without posterior vaginal wall prolapse between August 2018 and October 2022. We assessed the QOL before and after surgery using prolapse-QOL (P-QOL) questionnaires. All patients who received LSC or RSC with a single anterior mesh left the hospital as scheduled without severe perioperative complications. There were no instances of wound infection or vaginal mesh extrusion. The recovery rate of questionnaires was 63.5% (33/52). All QOL score domains improved significantly, and there were no questionnaire parameters that worsened. LSC or RSC using only a single anterior mesh improves P-QOL with a low incidence of surgical complications for POP patients who did not have posterior vaginal wall prolapse. LSC or RSC with a single anterior mesh may be a prospective new procedure for POP.
Shota Yamamoto, Ryosuke Arakaki, Hiroki Noguchi, Asuka Takeda, Maimi Uchishiba, Shuhei Kamada, Ayuka Mineda, Masafumi Kon, Riyo Kinouchi, Yuri Yamamoto, Kanako Yoshida, Takashi Kaji, Nobuo Shinohara and Takeshi Iwasa : Kisspeptin administration may promote precopulatory behavior in male rats independently or supplementally to testosterone and contribute to proceptive behavior in female partners, reducing mating failure, General and Comparative Endocrinology, Vol.353, 114528, 2024.
(要約)
Kisspeptin is a peptide that plays an important role through its effects on the hypothalamus-pituitary-gonadal (HPG) axis. It has also been implicated in sexual behavior. The present study investigated whether the relationship between kisspeptin and sexual behavior is independent of the HPG axis, i.e., testosterone. Sexual behavior was examined after the administration of kisspeptin to gonadally intact male rats and gonadectomized male rats that received testosterone supplementation. Other male rats were also observed for sexual behavior once a week from 2 to 5 weeks after gonadectomy and receiving kisspeptin for the sixth postoperative week. Sexual behavior in female rats serving as the partner for each male was also observed. Female rats were not administered kisspeptin in the present study. The results obtained showed that the administration of kisspeptin increased precopulatory behavior in gonadally intact male rats and gonadectomized male rats that received testosterone supplementation and proceptive behavior in their female partners. Precopulatory behavior in males and receptive behavior in females increased, while copulatory behavior in males and receptive behavior in females remained unchanged. Furthermore, the administration of kisspeptin increased precopulatory behavior in gonadectomized males, but did not affect receptive behavior in females. These results suggest that kisspeptin affected males independently and/or supplementally to testosterone, and also that changes in the presence of testosterone in males had an impact on proceptive behavior in their female partners. In conclusion, kisspeptin may involve an as-yet-unidentified neural pathway in sexual desire independently of the HPG axis.
(キーワード)
Animals / Kisspeptins / Male / Testosterone / Female / Rats / Sexual Behavior, Animal / Rats, Wistar / Copulation
Yuri Kadota, Takeshi Katou, Kana Kasai, Takako Kawakita, Misaki Murayama, Akari Shinya, Hikari Sasada, Sachiko Katayama, Mari Nii, Shota Yamamoto, Hiroki Noguchi, Kou Tamura, Hidenori Aoki, Miyu Taniguchi, Tomotaka Nakagawa, Takashi Kaji, Masato Nishimura, Riyo Kinouchi, Kanako Yoshida and Takeshi Iwasa : Expression of SMADs in orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model, Endocrine Journal, Vol.71, No.4, 395-401, 2024.
(要約)
Activin A promotes the development of endometriotic lesions in a murine model of endometriosis, and the immunohistochemical localization of phosphorylated suppressor of mothers against decapentaplegic homolog 2/3 (pSMAD2/3) complex in endometriotic lesions has been reported. Activin may therefore be involved in the development and proliferation of endometriotic cells via the SMAD signaling pathway. However, few detailed reports exist on SMAD7 expression in endometriosis. The purpose of this study was to investigate the expression of pSMAD2/3 or pSMAD3 and SMAD7 in the orthotopic human endometrium, ovarian endometriosis, and endometriotic lesions in a murine model and the effect of activin A on pSMAD2/3 and SMAD7 expression. We established an endometriosis murine model via the intraperitoneal administration of endometrial tissue and blood from donor mice. Activin A was intraperitoneally administered to the activin group. We immunohistochemically evaluated orthotopic endometria, ovarian endometriotic tissues, and endometriotic lesions in the murine model followed by western blotting. We found that pSMAD3 and SMAD7 were expressed in ovarian endometriosis and orthotopic endometria from patients with and without endometriosis. In the murine model, endometriotic lesions expressed pSMAD2/3 and SMAD7 in the activin and control groups, and higher SMAD7 expression was found in the activin group. To the best of our knowledge, this study is the first to show that SMAD7 expression is upregulated in endometriosis. In conclusion, these results suggest that activin A activates the SMAD signaling pathway and promotes the development of endometriotic lesions, thus identifying SMAD7 as a potential therapeutic target for endometriosis.
(キーワード)
Endometriosis / Female / Animals / Humans / Endometrium / Mice / Disease Models, Animal / Smad7 Protein / Smad3 Protein / Smad2 Protein / Activins / Ovarian Diseases / Adult / Signal Transduction
Polycystic ovary syndrome (PCOS) is associated with an increased risk of psychological distress as well as enhanced responses to psychosocial stress. Recently, it was hypothesized that PCOS patients may be at high risk of novel COVID-19 infections and worse clinical presentations during such infections. Here, we evaluated the effects of PCOS on stress responses to bacterial and viral mimetics using dihydrotestosterone-induced PCOS model rats. Lipopolysaccharide (LPS; a bacterial mimetic) or polyinosinic-polycytidylic acid (Poly-IC; a viral mimetic) was injected into PCOS model rats (PCOS) and non-PCOS rats (control), and the rats' stress responses were evaluated. In the PCOS group, the rats' anorectic and febrile responses to LPS injection were enhanced, whereas their anorectic and febrile responses to Poly-IC injection were unaltered. The PCOS group also exhibited greater changes in peripheral cytokine levels in response to LPS, but not Poly-IC. On the contrary, after the injection of Poly-IC depressed locomotor activity was more evident in the PCOS group, whereas no such changes were observed after LPS injection. These findings indicate that although the stress responses of PCOS model rats to infection may be enhanced, the patterns of change in stress responses and their underlying mechanisms may differ between bacterial and viral infections.
Kanako Yoshida, Takeshi Katou, Riyo Kinouchi, Hikari Sasada, Takashi Kaji and Takeshi Iwasa : Evaluation of Deeply Infiltrating Endometriosis by Preoperative Magnetic Resonance Imaging in Patients with Adenomyosis, Gynecology and Minimally Invasive Therapy, Vol.13, No.2, 105-110, 2024.
(要約)
Before endometriosis surgery, it is important to identify deep infiltrating endometriosis (DIE) to assess the surgical difficulty. Preoperative magnetic resonance imaging (MRI) was used to determine which findings are useful in predicting DIE. Between 2008 and 2016, 54 patients with adenomyosis underwent total laparoscopic hysterectomy at our hospital. We retrospectively evaluated the intraoperative findings and magnetic resonance imaging (MR) images. The MR images were scored based on the presence of five findings: retroflexed uterus, elevated posterior vaginal fornix, intestinal tethering in the direction of the uterus, faint strands between the uterus and intestine, and fibrotic nodules covering the serosal surface of the uterus. Of the five findings, intestinal tethering and faint strands between the uterus and intestine showed a sensitivity of 73% and a specificity of 91%-100%, indicating the usefulness of these findings for detecting deep endometriosis lesions. However, finding a retroflexed uterus did not contribute to DIE lesion detection. The sensitivities of an elevated posterior fornix and fibrotic nodules covering the surface of the uterus were as low as 46%-59%, and their specificities were as high as 84%-91%. Preoperative preparation is essential for patients with intestinal tethering or faint strands between the uterus and intestine on preoperative MRI after obtaining appropriate informed consent.
Tomohiro Kagawa, Ayuka Mineda, Tomotaka Nakagawa, Ayaka Shinohara, Ryosuke Arakaki, Hiroaki Inui, Hiroki Noguchi, Atsuko Yoshida, Riyo Kinouchi, Yuri Yamamoto, Kanako Yoshida, Takashi Kaji, Masato Nishimura and Takeshi Iwasa : New treatment strategies for uterine sarcoma using secreted frizzledrelated proteins, Experimental and Therapeutic Medicine, Vol.27, No.5, 231, 2024.
(要約)
Secreted frizzled-related proteins (SFRPs) are involved in the development of various types of cancer and function by suppressing the Wnt signaling pathway. To elucidate the clinical implications of SFRPs in uterine sarcoma, SFRP expression levels and their effects on uterine leiomyosarcoma cells were examined. Immunostaining for SFRP4 was performed on uterine smooth muscle, uterine fibroid and uterine leiomyosarcoma tissues. Additionally, the effects of SFRP4 administration on cell viability, migration and adhesion were evaluated in uterine leiomyosarcoma SKN cells using the WST-1 assay (Roche Diagnostics) and the CytoSelect™ 24-well Cell Migration Assay Kit and the CytoSelect™ 48-well Cell Adhesion Assay Kit. The expression levels of SFRP4 in uterine leiomyosarcoma tissues were lower than those in normal smooth muscle and uterine fibroid tissues. In addition, SFRP4 suppressed the viability and migration, and increased the adhesion ability of uterine leiomyosarcoma cells compared with in the control group. In conclusion, SFRP4 may suppress the viability and migration, and enhance the adhesion of sarcoma cells. These results suggested that SFRP4 could be considered as a novel therapeutic target for uterine sarcoma.
While the effects of progesterone on body weight and appetite in pre-menopausal conditions have been well elucidated, its effects in post-menopausal conditions have not been clarified. On the contrary, the effects of estrogen on body weight and appetite in post-menopausal conditions have been well established. In this study, the effects of progesterone treatment on body weight, appetite, and fat mass in ovariectomized rats were evaluated. In addition, the central and/or peripheral levels of oxytocin (OT), leptin, and their receptors, which are potent anorectic factors, were examined. Female rats were ovariectomized and divided into control, progesterone-treated, and estrogen-treated groups. Body weight, food intake, and subcutaneous fat mass were lower in both the progesterone and estrogen groups than in the control group. The estrogen group exhibited higher serum OT levels than the control group, whereas the OT levels of the progesterone and control groups did not differ. The serum leptin levels of both the progesterone and estrogen groups were lower than those of the control group. Gene expression analysis of OT, leptin, and their receptors in the hypothalamus and adipose tissue found few significant differences among the groups. Hypothalamic neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) mRNA levels involved in appetite regulation were slightly altered in the progesterone and estrogen groups. These findings suggest that progesterone treatment may have favorable effects on body weight, appetite, and fat mass regulation in post-menopausal conditions and that the mechanisms underlying these effects of progesterone differ from those underlying the effects of estrogen.
Junki Imaizumi, Kanako Yoshida, Hiroki Noguchi, Takaaki Maeda, Takeshi Kato and Takeshi Iwasa : A Safe Laparoscopic Approach for Ovarian Tumors during Pregnancy, Gynecology and Minimally Invasive Therapy, Vol.13, No.1, 19-24, 2024.
(要約)
Surgery for pregnant women with ovarian tumors poses the risk of uterine irritation. We aimed to demonstrate the superiority of our laparoscopic technique over conventional methods and to compare the outcomes of laparoscopy with those of laparotomy for ovarian tumors during pregnancy. This retrospective study included 50 patients undergoing procedures for ovarian tumors during pregnancy at the Tokushima University Hospital between January 2005 and December 2021. We compared surgical outcomes between laparoscopic procedures and laparotomy, along with complications. In addition, we compared the frequency of uterine stimulation with the conventional trocar position to that with the currently used trocar position in laparoscopic surgery. Forty patients in the laparoscopy group and 10 in the laparotomy group underwent procedures. The laparoscopy group had less bleeding (16.4 ± 28.8 vs. 58 ± 72.2 mL, P < 0.05) and shorter hospital stays (7.6 ± 1.7 vs. 12.8 ± 13.1 days, P < 0.05) compared with those of the laparotomy group. The outcomes showed no significant differences between groups. All laparoscopies and laparotomies were successful and without complications. Furthermore, the current trocar position tended to stimulate the uterus less frequently. The results suggested that, compared to laparotomy, laparoscopy for ovarian tumors during pregnancy had better outcomes. The trocar position in our technique allows for easy operation of ovarian tumors without interference by forceps or cameras, resulting in minimal irritation of the uterus. Our original laparoscopic method may be safer with superior outcomes over the conventional method.
(キーワード)
Laparoscopy / laparotomy / pregnancy / trocar position
Kanako Yoshida, Takeshi Katou, Riyo Kinouchi, Hikari Sasada, Takashi Kaji and Takeshi Iwasa : Evaluation of deeply infiltrating endometriosis by preoperative magnetic resonance imaging in patients with adenomyosis, Gynecology and Minimally Invasive Therapy, Vol.13, No.2, 105-110, 2023.
(要約)
Before endometriosis surgery, it is important to identify deep infiltrating endometriosis (DIE) to assess the surgical difficulty. Preoperative magnetic resonance imaging (MRI) was used to determine which findings are useful in predicting DIE. Between 2008 and 2016, 54 patients with adenomyosis underwent total laparoscopic hysterectomy at our hospital. We retrospectively evaluated the intraoperative findings and magnetic resonance imaging (MR) images. The MR images were scored based on the presence of five findings: retroflexed uterus, elevated posterior vaginal fornix, intestinal tethering in the direction of the uterus, faint strands between the uterus and intestine, and fibrotic nodules covering the serosal surface of the uterus. Of the five findings, intestinal tethering and faint strands between the uterus and intestine showed a sensitivity of 73% and a specificity of 91%-100%, indicating the usefulness of these findings for detecting deep endometriosis lesions. However, finding a retroflexed uterus did not contribute to DIE lesion detection. The sensitivities of an elevated posterior fornix and fibrotic nodules covering the surface of the uterus were as low as 46%-59%, and their specificities were as high as 84%-91%. Preoperative preparation is essential for patients with intestinal tethering or faint strands between the uterus and intestine on preoperative MRI after obtaining appropriate informed consent.
Ayako Suto, Yuya Yano, Yuri Yamamoto, Hiroki Noguchi, Asuka Takeda, Shota Yamamoto, Tomohiro Kagawa, Kanako Yoshida, Kenji Hinokio, Akira Kuwahara, Toshiyuki Yasui and Takeshi Iwasa : Effects of activation with a Ca ionophore and roscovitine on the development of human oocytes that failed to fertilize after ICSI., The Journal of Medical Investigation : JMI, Vol.70, No.3.4, 321-324, 2023.
(要約)
Sequential treatment with an Ca ionophore and roscovitine activates oocytes that remain unfertilized after ICSI. In TESE-ICSI, the activation rate tended to be increased by the co-administration of roscovitine with a Ca ionophore. J. Med. Invest. 70 : 321-324, August, 2023.
乳癌患者 / 遺伝性乳癌卵巣癌症候群患者 / リスク低減卵管卵巣摘出術 / breast cancer patients / hereditary breast and ovarian cancer syndrome(HBOC) / risk reducing salpingo-oophorectomy (RRSO)
Takako Kawakita, Toshiyuki Yasui, Kanako Yoshida, Sumika Matsui and Takeshi Iwasa : Correlations of Androstenediol with Reproductive Hormones and Cortisol According to Stages during the Menopausal Transition in Japanese Women. J, The Journal of Steroid Biochemistry and Molecular Biology, Vol.214, 106009, 2021.
(要約)
Associations of androstenediol, which has both androgenic and estrogenic activities, with circulating reproductive hormones and stress hormone in women during the menopausal transition may be different depending on the menopausal stage. The aim of this study was to determine the changes in circulating androstenediol during the menopausal transition in Japanese women and the associations of androstenediol with estrogen, androgen and cortisol for each stage of the menopausal transition. We divided the 104 subjects into 6 stages by menstrual regularity and follicle-stimulating hormone level: mid reproductive stage, late reproductive stage, early menopausal transition, late menopausal transition, very early postmenopause and early postmenopause. Levels of dehydroepiandrosterone sulfate (DHEAS), estradiol, estrone, testosterone (T), free T, androstenedione and cortisol were measured. Serum androstenediol concentration was measured by using liquid chromatography mass spectrometry. There were no significant differences in androstenediol levels among the 6 stages. Levels of DHEA-S and testosterone showed significant and positive correlations with androstenediol in all stages. Estradiol levels showed negative correlations with androstenediol levels in the late menopausal transition and very early postmenopause (r=-0.452, p = 0.052 and r=-0.617, p = 0.006, respectively). Cortisol levels showed significant and positive correlations with androstenediol levels in the mid and late reproductive stages (r = 0.719, p = 0.003 and r = 0.808, p < 0.001, respectively).The associations of androstenediol with estradiol and cortisol were different depending on the stage of the menopausal transition. Androstenediol may play a compensatory role for estrogen deficiency from late menopausal transition to very early postmenopause.
Takako Kawakita, Takeshi Iwasa, Shuhei Kamada, Kanako Yoshida and Takeshi Katou : Effects of gonadal status and the estrogen milieu on hypothalamic oxytocin gene expression and serum oxytocin levels in female rats., Hormones and Behavior, Vol.133, No.8, 105005, 2021.
(要約)
Oxytocin (OT) and its receptor (OTR) play various roles in the central and peripheral regulation of appetite and body weight. Previously, we have shown that the administration of OT markedly decreased appetite and body weight gain in ovariectomized (OVX) obese rats. In addition, recent studies have shown that the endogenous OT system is also affected by endogenous or exogenous estrogen. In this study, we showed that ovariectomy decreased rats' hypothalamic OT/OTR mRNA and serum OT levels, but did not affect their visceral fat OTR mRNA levels. The chronic administration of estradiol (E2) abrogated these ovariectomy-induced changes; i.e., it increased the rats' hypothalamic OT/OTR mRNA and serum OT levels, and may be associated with reductions in food intake and body weight gain. In addition, acute E2 administration increased the rats' hypothalamic OTR mRNA and serum OT levels, but did not affect their hypothalamic OT mRNA levels. Taken together, these results suggest that endogenous OT and/or OTR expression might be positively regulated by E2 and that the suppressive effects of E2 on appetite and body weight gain might be mediated, at least in part, by the OT system. Thus, we consider that OT might be a target hormone to pursue subsequent interventions of menopause for menopause-induced metabolic disorders.
Kana Kasai, Takeshi Katou, Yuri Kadota, Otgontsetseg Erdenebayar, Kaoru Keyama, Takako Kawakita, Kanako Yoshida, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Intraperitoneal administration of activin A promotes development of endometriotic lesions in a mouse model of endometriosis., The Journal of Medical Investigation : JMI, Vol.66, No.1.2, 123-127, 2019.
(要約)
This study aimed to investigate the effect of intraperitoneal administration of activin on the occurrence of endometriosis using a mouse model of endometriosis. A mouse model of endometriosis was prepared by intraperitoneally administering endometrial tissue and blood collected from donor mice to C57BL/6J 7-8- week-old recipient mice. A total of 400 μg of activin A was intraperitoneally administered to model mice in the activin group for 5 days. Intraperitoneal endometriotic lesions were confirmed macroscopically and IL-6 and TNF-α levels in washed ascites were measured by ELISA. Endometriotic lesions were observed in all mice. In the activin group, the maximum diameter of endometriotic lesions was significantly larger than that in control group (4.7?1.3 vs 2.9?0.9 mm, p?0.01). The total area of the lesion was also significantly higher in the activin group than in the control group (21.1?9.9 vs 8.8?5.4 mm,p?0.01). Furthermore, IL-6 and TNF-α levels in ascites were significantly higher in the activin group than in the control group (IL-6 : 85.8?15.3 vs 75.1?19.3 pg/ml, p?0.05 ; TNF-α : 629.8?15.4 vs 605.9?11.4 pg/ml, p?0.05). Activin promotes occurrence of endometriosis. Inflammatory cytokines are also elevated by activin administration,suggesting that they may contribute to progression of endometriosis J. Med. Invest. 66 : 123-127, February, 2019.
Kaoru Keyama, Takeshi Katou, Yuri Kadota, Otgontsetseg Erdenebayar, Kana Kasai, Takako Kawakita, Anna Tani, Sumika Matsui, Takeshi Iwasa, Kanako Yoshida, Masahiko Maegawa, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Lipopolysaccharide promotes early endometrial-peritoneal interactions in a mouse model of endometriosis., The Journal of Medical Investigation : JMI, Vol.66, No.1.2, 70-74, 2019.
(要約)
The aims of this study were to clarify the effects of lipopolysaccharide (LPS) on the early development of endometriosis and on the production of cytokines and chemokines in the murine peritoneal cavity. Endometriotic lesions were induced in C57BL/6J adult female mice by intraperitoneal injection of endometrial fragments plus blood or endometrial fragments plus blood with LPS. On day 7, endometriotic lesions were assessed by gross and microscopic evaluations. Time-dependent changes in the secretion of TNF-α,IL-6,and CXCL2/MIP-2 in peritoneal lavage fluid after the intraperitoneal injection of LPS (50 µg/body) were measured by their respective enzyme-linked immunosorbent assays. The areas of endometriotic lesions in the LPS group (10.8 8.6 mm) were significantly larger than those in the control group (3.1 3.7 mm).The levels of TNF-α and IL-6 peaked within 2 hours and the level of MIP-2 reached a maximum on day 1 after the injection of LPS. LPS promotes development of the early stages of murine endometriotic lesions. J. Med. Invest. 66 : 70-74, February, 2019.
Kanako Yoshida, Masato Nishimura, Akiko Abe, Takeshi Katou, Hiroyuki Furumoto and Minoru Irahara : Can systematic lymphadenectomy be omitted for low-risk endometrial cancer?, The Journal of Medical Investigation : JMI, Vol.65, No.3,4, 221-224, 2018.
(要約)
The objective of this study was to identify pathological indicators that could be used to identify a subgroup of patients with apparent stage I endometrial cancer who do require retroperitoneal lymphadenectomy. 188 T1 endometrial cancer patients underwent primary surgery at Tokushima University Hospital. We retrospectively evaluated their clinical records and histopathological factors. Systematic lymphadenectomy was performed for 149 patients, and 39 patients (grade 1 with < 5 mm of myometrial invasion) were treated without lymphadenectomy. Lymph node metastases were found in 19 (12.8%) of the lymphadenectomy cases. Twenty-four patients with a T1a endometrium-limited lesion did not exhibit lymph node metastasis. Three (3.1%) of the 95 patients with a T1a lesion exhibited lymph node metastasis, and these 3 cases exhibited approximately 50% myometrial invasion. The 39 low-risk patients who did not undergo systematic lymphadenectomy remain alive without recurrence. Systematic lymphadenectomy could be omitted for patients with a grade 1 tumor and minor myometrial invasion of less than 5mm. J. Med. Invest. 65:221-224, August, 2018.
Sumika Matsui, Toshiyuki Yasui, Kana Kasai, Kanako Yoshida, Takeshi Katou, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Circulating dehydroepiandrosterone-sulphate decreases even with a slight change in oestradiol., Journal of Obstetrics and Gynaecology, Vol.38, No.2, 231-235, 2017.
(要約)
The aim of this study was to determine the effect of hormone replacement therapy (HRT) on changes in circulating dehydroepiandrosterone-sulphate (DHEA-S) with focus on the relationship between oestrogen level and change in DHEA-S. Forty-two women were enrolled in this longitudinal study. Nineteen women received oral oestradiol and twenty-three women received transdermal oestradiol continuously. Twenty women received progesterone continuously except for women who had undergone hysterectomy. Circulating oestradiol, follicle-stimulating hormone, luteinising hormone and DHEA-S levels before and at 3 months after commencement of HRT were measured. Circulating DHEA-S level was significantly decreased at 3 months (p < .001). Oestradiol level at 3 months ranged from 6.5 pg/ml to 159 pg/ml. There was no significant correlation of ΔDHEA-S (DHEAS level at 3 months-DHEA-S level at baseline) with Δoestradiol (r = 0.114, p = .471). Circulating DHEA-S level was significantly decreased at 3 months in all the four quartiles and divided according to Δoestradiol, and ΔDHEA-S did not show significant differences. In conclusion, circulating DHEA-S decreases even with a slight increase in oestradiol level. Impact statement What is already known on this subject: A transient increase in DHEA-S in women during the menopausal transition may be involved in the occurrence of menopausal symptoms and/or unfavourable metabolic changes. Hormone replacement therapy decreases circulating DHEA-S level. However, dose dependency of the change in DHEA-S on oestrogen has not been reported. What the results of this study add: Circulating DHEA-S decreases even with a slight increase in oestradiol level. What the implications are of these findings for clinical practice and/or further research: Adrenal function may respond to a small change in oestrogen.
Sumika Matsui, Toshiyuki Yasui, Kana Kasai, Kaoru Keyama, Kanako Yoshida, Takeshi Katou, Hirokazu Uemura, Akira Kuwahara, Toshiya Matsuzaki and Minoru Irahara : Sex hormone-binding globulin and antithrombin III activity in women with oral ultra-low-dose estradiol., Journal of Obstetrics and Gynaecology, Vol.37, No.5, 627-632, 2017.
(要約)
Oral oestrogen increases the risk of venous thromboembolism (VTE) and increases production of sex hormone-binding globulin (SHBG) in a dose-dependent manner. SHBG has been suggested to be involved in venous thromboembolism. We examined the effects of oral ultra-low-dose oestradiol on circulating levels of SHBG and coagulation parameters, and we compared the effects to those of transdermal oestradiol. Twenty women received oral oestradiol (500 g) every day (oral ultra-low-dose group) and 20 women received a transdermal patch (50 g) as a transdermal group. In addition, the women received dydrogesterone continuously (5g) except for women who underwent hysterectomy. Circulating SHBG, antithrombin III (ATIII) activity, d-dimer, thrombin-antithrombin complex and plasmin- 2 plasmin inhibitor complex were measured before and 3 months after the start of treatment. SHBG was significantly increased at 3 months in the oral ultra-low-dose group, but not in the transdermal group. However, percent changes in SHBG were not significantly different between the two groups. In both groups, ATIII was significantly decreased at 3 months. In conclusion, even ultra-low-dose oestradiol orally increases circulating SHBG level. However, the magnitude of change in SHBG caused by oral ultra-low-dose oestradiol is small and is comparable to that caused by transdermal oestradiol. Impact statement Oral oestrogen replacement therapy increases production of SHBG which may be related to increase in VTE risk. However, the effect of oral ultra-low-dose oestradiol on SHBG has not been clarified. Even ultra-low-dose oestradiol orally increases circulating SHBG levels, but the magnitude of change in SHBG caused by oral ultra-low-dose oestradiol is small and is comparable to that caused by transdermal oestradiol. VTE risk in women receiving oral ultra-low-dose oestradiol may be comparable to that in women receiving transdermal oestradiol.
Takeshi Katou, Kaoru Keyama, Sumika Matsui, Mikio Yamasaki, Kanako Yoshida and Minoru Irahara : Step Up from Salpingo-Oophorectomy to Total Laparoscopic Hysterectomy Incorporating Incision Dissectiong Procedures., Journal of Minimally Invasive Gynecology, Vol.22, No.6S, S217, 2015.
Yasuyo Saijo, Hiroyuki Furumoto, Kanako Yoshida, Masato Nishimura and Minoru Irahara : Clinical Significance of Vascular Endothelial Growth Factor Expression and Microvessel Density in Invasive Cervical Cancer, The Journal of Medical Investigation : JMI, Vol.62, No.3-4, 154-160, 2015.
(要約)
To determine whether vascular endothelial growth factor (VEGF) expression and microvessel density are predictive of prognosis in cases of invasive cervical cancer, correlations among VEGF expression, microvessel density, and clinicopathological parameters were identified. VEGF expression was evaluated in 50 cervical cancer samples by immunohistochemical staining. Microvessel density was assessed by immunostaining for CD31-positive endothelial cells in the most vascularized areas of tumors. VEGF expression and microvessel density were significantly higher in adenocarcinomas than in squamous cell carcinomas. However, in cases of adenocarcinoma, no significant correlations were found among VEGF expression, microvessel density, and clinicopathological parameters. In contrast, for squamous cell carcinomas, microvessel density was significantly higher in cases at an advanced stage and in those with several other poor prognostic factors. The finding that cervical adenocarcinomas exhibited greater VEGF expression and microvessel density than squamous cell carcinomas may explain the poorer prognosis of adenocarcinoma compared with squamous cell carcinoma. Moreover, microvessel density in squamous cell carcinomas was significantly correlated with poor prognostic factors. Therefore, there is possibility that bevacizumab, a humanized monoclonal antibody against VEGF-A, may be useful in the initial treatment targeting angiogenesis for early-stage cervical cancer.
Yasuyo Saijo, Hiroyuki Furumoto, Kanako Yoshida, Masato Nishimura and Minoru Irahara : Clinical Significance of Vascular Endothelial Growth Factor Expression and Microvessel Density in Invasive Cervical Cancer., The Journal of Medical Investigation : JMI, Vol.62, No.3-4, 154-160, 2015.
(要約)
To determine whether vascular endothelial growth factor (VEGF) expression and microvessel density are predictive of prognosis in cases of invasive cervical cancer, correlations among VEGF expression, microvessel density, and clinicopathological parameters were identified. VEGF expression was evaluated in 50 cervical cancer samples by immunohistochemical staining. Microvessel density was assessed by immunostaining for CD31-positive endothelial cells in the most vascularized areas of tumors. VEGF expression and microvessel density were significantly higher in adenocarcinomas than in squamous cell carcinomas. However, in cases of adenocarcinoma, no significant correlations were found among VEGF expression, microvessel density, and clinicopathological parameters. In contrast, for squamous cell carcinomas, microvessel density was significantly higher in cases at an advanced stage and in those with several other poor prognostic factors. The finding that cervical adenocarcinomas exhibited greater VEGF expression and microvessel density than squamous cell carcinomas may explain the poorer prognosis of adenocarcinoma compared with squamous cell carcinoma. Moreover, microvessel density in squamous cell carcinomas was significantly correlated with poor prognostic factors. Therefore, there is possibility that bevacizumab, a humanized monoclonal antibody against VEGF-A, may be useful in the initial treatment targeting angiogenesis for early-stage cervical cancer.
Kanako Yoshida, Hiroyuki Furumoto, Akiko Abe, Takeshi Katou, Masato Nishimura and Minoru Irahara : The possibility of vertical transmission of human papillomavirus through maternal milk, Journal of Obstetrics and Gynaecology, Vol.31, No.6, 503-506, 2011.
(要約)
Human papillomavirus (HPV) DNA has been detected in the oral cavity of infants and breast cancer tissue, suggesting its vertical transmission through maternal milk. We determined whether HPV is detected in maternal milk and is vertically transmitted by breast-feeding. Informed consent was obtained, and maternal milk samples (n=80) were analysed for high-risk HPV DNA. In 43 women, this DNA was measured in the uterine cervix. In women with positive samples, this DNA was measured in the oral cavities of their children. The domain including HPV E6 and E7 was amplified by polymerase chain reaction using consensus primers, and HPV serotype determined by electrophoresis after restriction enzyme digestion. High-risk HPV-16 was detected in two of 80 samples (2.5%), and in these two cases, high-risk HPV was not detected in the uterine cervix or oral cavity of the child. It was concluded that the infection of HPV in maternal milk is rare (2/80); vertical transmission through maternal milk was not detected in this study (0/80). HPV infection through maternal milk may occur, but its likelihood is low.
Akiko Abe, Hiroyuki Furumoto, Kanako Yoshida, Takeshi Katou, Yasuyo Saijo and Minoru Irahara : Gene gun-mediated skin transfection with FL gene suppresses the growth of murine fibrosarcoma., The Journal of Medical Investigation : JMI, Vol.58, No.1-2, 39-45, 2011.
(要約)
Particle-mediated transfection is known as an efficient method of non-viral gene transfer. Flt3 ligand (FL) is a growth factor for hematopoietic progenitors; it promotes the growth of dendritic cells (DC). DCs are powerful antigen-presenting cells (APCs) and show a remarkable capacity to stimulate antigen-specific T-cell responses. In this study, we intended to investigate the suppressive effect on tumor growth by gene gun-mediated transfer of FL in a murine model. C57BL/6J mice were injected intradermally with MCA205 cells. DNA (pNGVL-hFLex)-coated gold particles were delivered to the mouse skin surrounding the target tumor. The expression of FL was determined by RT-PCR. Analyses by immunohistochemistry and fluorescence-activated cell sorter (FACS) revealed an increase in the number of DC after treatment with FL. Gene gun-mediated pNGVL-hFLex transfer significantly inhibited the growth of the MCA205 tumor. FL transfer markedly increased the number of CD11c(+) DCs in the tumor tissue. Further, the FL-transfected mice exhibited a significantly higher number of CD80(+) MHC-II cells. We successfully performed FL therapy using an in vivo gene gun in order to effectively mobilize DCs in situ and induce suppressive immunity.
Akiko Abe, Hiroyuki Furumoto, Kanako Yoshida, Takeshi Katou, Yasuyo Saijo and Minoru Irahara : Gene gun-mediated skin transfection with FL gene suppresses the growth of murine fibrosarcoma., The Journal of Medical Investigation : JMI, Vol.58, No.1-2, 39-45, 2011.
(要約)
Particle-mediated transfection is known as an efficient method of non-viral gene transfer. Flt3 ligand (FL) is a growth factor for hematopoietic progenitors; it promotes the growth of dendritic cells (DC). DCs are powerful antigen-presenting cells (APCs) and show a remarkable capacity to stimulate antigen-specific T-cell responses. In this study, we intended to investigate the suppressive effect on tumor growth by gene gun-mediated transfer of FL in a murine model. C57BL/6J mice were injected intradermally with MCA205 cells. DNA (pNGVL-hFLex)-coated gold particles were delivered to the mouse skin surrounding the target tumor. The expression of FL was determined by RT-PCR. Analyses by immunohistochemistry and fluorescence-activated cell sorter (FACS) revealed an increase in the number of DC after treatment with FL. Gene gun-mediated pNGVL-hFLex transfer significantly inhibited the growth of the MCA205 tumor. FL transfer markedly increased the number of CD11c(+) DCs in the tumor tissue. Further, the FL-transfected mice exhibited a significantly higher number of CD80(+) MHC-II cells. We successfully performed FL therapy using an in vivo gene gun in order to effectively mobilize DCs in situ and induce suppressive immunity.
Takeshi Iwasa, Hiroki Noguchi, Risa Tanano, Erika Yamanaka, Asuka Takeda, Kou Tamura, Hidenori Aoki, Tatsuro Sugimoto, Hikari Sasada, Takaaki Maeda, Saki Minato, Shota Yamamoto, Hiroaki Inui, Tomohiro Kagawa, Atsuko Yoshida, Ayuka Mineda, Mari Nii, Riyo Kinouchi, Kanako Yoshida, Yuri Yamamoto and Takashi Kaji : Age-Dependent Changes in the Effects of Androgens on Female Metabolic and Body Weight Regulation Systems in Humans and Laboratory Animals., International Journal of Molecular Sciences, Vol.24, No.23, 16567, 2023.
(要約)
In recent years, the effects of androgens on metabolic and body weight regulation systems and their underlying mechanisms have been gradually revealed in females. In women and experimental animals of reproductive age, androgen excess can adversely affect metabolic functioning, appetite, and body weight regulation. In addition, excess androgens can increase the risk of metabolic disorders, such as obesity, insulin resistance, and diabetes. These unfavorable effects of androgens are induced by alterations in the actions of hypothalamic appetite-regulatory factors, reductions in energy expenditure, insulin resistance in skeletal muscle, and β-cell dysfunction. Interestingly, these unfavorable effects of androgens on metabolic and body-weight regulation systems are neither observed nor evident in ovariectomized animals and post-menopausal women, indicating that the adverse effects of androgens might be dependent on the estrogen milieu. Recent findings may provide novel sex- and age-specific strategies for treating metabolic diseases.
Ryosuke Arakaki, Kanako Yoshida, Junki Imaizumi, Takashi Kaji, Takeshi Kato and Takeshi Iwasa : Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome: A case report., International Journal of Surgery Case Reports, Vol.107, 108368, 2023.
(要約)
We report that a combined laparoscopic and transvaginal approach was useful for treating OHVIRA with oviductal hematoma.