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.
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.
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.
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.