Purevdorj Tugsjargal, Arata Moeka, Mari Nii, Yamamoto Shota, Hiroki Noguchi, Asuka Takeda, Aoki Hidenori, 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.
2.
Hiroki Noguchi, ARATA Moeka, Saki Minato, Kou Tamura, AOKI Hidenori, Asuka Takeda, Yuri Yamamoto, 平田 寛之, Takeshi Iwasa and Toshiya Matsuzaki : 多囊胞性卵巣症候群の診断におけるアクセス試薬を用いた血中LH基礎値及びLH/FSH比のカットオフ値の設定と内分泌異常の発現率に関する検討, Japanese Journal of Medicine and Pharmaceutical Science, Vol.82, No.3, 2025.
3.
Hiroki Noguchi, Akira Iwase, Takeshi Iwasa, Haruhiko Kanasaki, Fuminori Kimura, Koji Kugu, Kazuki Saito, Tsuyoshi Baba, Tetsuaki Hara, Saki Minato, Rie Yanagihara and Toshiya Matsuzaki : Japan Society of Obstetrics and Gynecology revised diagnostic criteria for polycystic ovary syndrome: JSOG2024 criteria, The Journal of Obstetrics and Gynaecology Research, Vol.51, No.1, e16152, 2025.
(Summary)
Japanese patients with polycystic ovary syndrome (PCOS) exhibit distinct body type characteristics, such that the rate of overweight/obese women is remarkably low. In addition, hyperandrogenism is relatively rare among Japanese PCOS patients. Therefore, these factors are considered in PCOS diagnostic criteria used in Japan. Diagnostic criteria for PCOS were recently revised by the Japan Society of Obstetrics and Gynecology based on a nationwide survey of PCOS and released on December 5, 2023 (JSOG2024). JSOG2024 criteria diagnosed PCOS according to the following three items: (1) irregular menstrual cycle/chronic anovulation, (2) polycystic ovarian morphology or elevated serum anti-Müllerian hormone (AMH) level, and (3) hyperandrogenism or high luteinizing hormone. The presence of all three items is required to diagnose PCOS, after excluding other diseases with symptoms similar to PCOS. We also established AMH cut-off values by age and a system for evaluating ovarian findings useful for both the JSOG2024 and Rotterdam criteria. We anticipate that the JSOG2024 criteria with cut-off values will enhance the treatment of Japanese patients with PCOS and those of other ethnicities with low obesity and hirsutism.
Hiroki Noguchi, Takeshi Iwasa, Akira Iwase, Haruhiko Kanasaki, Fuminori Kimura, Koji Kugu, Kazuki Saito, Tsuyoshi Baba, Tetsuaki Hara and Toshiya Matsuzaki : Phenotypes and clinical laboratory data for polycystic ovary syndrome cases: A nationwide survey in Japan, The Journal of Obstetrics and Gynaecology Research, Vol.50, No.12, 2346-2356, 2024.
(Summary)
Describe the current phenotypes and clinical laboratory data regarding polycystic ovary syndrome (PCOS) in Japan, taking into account ethnic differences and obesity status. Data for 986 PCOS cases and 965 control cases were collected using a nationwide survey in Japan. Obese/overweight (body mass index [BMI] ≥25 kg/m) and non-obese/overweight (BMI <25 kg/m) cases were compared. Japanese PCOS cases predominantly involved non-obese/overweight patients, accounting for 75% of all cases. Among non-obese/overweight PCOS cases, the incidence of both amenorrhea and clinical/biochemical hyperandrogenism was significantly lower than in obese/overweight PCOS cases, whereas the rate of elevated serum luteinizing hormone (LH) level was significantly higher. Even though the incidence of hirsutism in Japan is only 13.5%, the detection rate for hyperandrogenism increased by as much as 30.4% when hirsutism was added to the Japan Society of Obstetrics and Gynecology (JSOG) criteria for the diagnosis of hyperandrogenism in addition to elevated serum total testosterone level. When evaluated based on timing of blood sampling, the LH level and LH/follicle-stimulating hormone ratio determined at the initial consultation involving a chief complaint of irregular menstrual cycle (after confirming the absence of follicles measuring ≥1 cm in diameter) were significantly higher than on days 2-3 or 4-6 of the menstrual cycle. Ethnic differences, including obesity status, affected the phenotype and clinical laboratory data of Japanese PCOS patients, such as the incidence rates of clinical/biochemical hyperandrogenism and the rate of elevated basal LH level. Adding hirsutism to the JSOG 2024 criteria would enhance the accuracy of PCOS diagnosis and enhance consistency with the Rotterdam 2003 criteria. Measuring basal LH level is useful for assessing the endocrinologic characteristics of Japanese PCOS cases, as well as lean Asian PCOS cases, but the timing of blood sampling can affect the result.
Arata Moeka, Kou Tamura, Aoki Hidenori, 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.
(Summary)
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.
(Summary)
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.
Hiroki Noguchi, Takeshi Iwasa, Akira Iwase, Haruhiko Kanasaki, Fuminori Kimura, Koji Kugu, Kazuki Saito, Tsuyoshi Baba, Tetsuaki Hara and Toshiya Matsuzaki : Cut-off value for anti-Müllerian hormone in the diagnostic criteria for polycystic ovary syndrome in the Japanese population, The Journal of Obstetrics and Gynaecology Research, Vol.50, No.8, 1368-1382, 2024.
(Summary)
To establish cut-off values for anti-Müllerian hormone (AMH) and antral follicle count (AFC) in the diagnostic criteria for polycystic ovary syndrome (PCOS) applicable to the Japan Society of Obstetrics and Gynecology (JSOG) 2024 criteria and the Rotterdam/International Evidence-Based Guideline for the assessment and management of PCOS (IEBG) 2023 criteria based on a nationwide survey, respectively, taking into account age, assays, and structure of the diagnostic criteria. Data were collected for 986 PCOS cases and 965 control cases using a national survey in Japan and used to establish cut-off values for AMH and AFC. Serum AMH levels were significantly higher in the PCOS group compared to the control group. Serum AMH showed a significant negative correlation with age and significant positive correlation with AFC in both groups. In multiple regression analysis, serum AMH level was independently affected by AFC and total testosterone. AMH cut-off values suitable for the JSOG 2024 criteria and the Rotterdam/IEBG 2023 criteria were separately established for the 20-29 and 30-39 years of age groups, respectively, and for Access, Lumipulse and Elecsys/ECLusys, respectively. AFC cut-off values suitable for the JSOG 2024 criteria and Rotterdam/IEBG 2023 criteria were also established separately. AFC exhibited statistically greater variability than AMH. The serum AMH level is the biochemical representation of ovarian findings in PCOS and considered objective and highly reliable. Therefore, it could serve as a surrogate for AFC as a marker of polycystic ovarian morphology in diagnostic criteria.
(Keyword)
Humans / Polycystic Ovary Syndrome / Anti-Mullerian Hormone / Female / Adult / Japan / Young Adult / Ovarian Follicle / Reference Values / East Asian People
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.
(Summary)
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.
(Keyword)
Animals / Kisspeptins / Male / Testosterone / Female / Rats / Sexual Behavior, Animal / Rats, Wistar / Copulation
Takeshi Iwasa, Hiroki Noguchi and Kou Tamura : 排卵障害 管理のポイントと新規治療薬の使い方, Clinical Gynecology and Obstetrics, Vol.78, No.5, 438-443, 2024.
12.
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.
(Summary)
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.
(Keyword)
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.
Takeshi Iwasa, Hiroki Noguchi and Shuhei Kamada : 治療法の再整理とアップデートのために 専門家による私の治療 多囊胞性卵巣症候群, Japan Medical Journal, Vol.5215, 47-48, 2024.
15.
Asuka Takeda, Yuri Yamamoto, Kou Tamura, Hidenori Aoki, Hiroki Noguchi, Saki Minato, Shuhei Kamada, Ryosuke Arakaki, Takashi Kaji and Takeshi Iwasa : Oncologic, fertility, and obstetric outcomes with MPA therapy in women with endometrial cancer and atypical endometrial hyperplasia, The Journal of Obstetrics and Gynaecology Research, Vol.50, No.4, 633-638, 2024.
(Summary)
Medroxyprogesterone acetate (MPA) is one of the treatments of atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) to preserve the fertility. Efficacy of MPA therapy and fertility and obstetric outcomes after remission were evaluated in EC or AEH patients. Among patients diagnosed with EC or AEH at Tokushima University Hospital between January 2002 and October 2020, we retrospectively analyzed patients, ages range from 26 to 40, who underwent conservative management using MPA (400-600 mg/day). In total, 19 patients underwent MPA therapy. The 18 (94%) patients achieved complete response (CR), and 1 (5%) patient achieved partial response (PR). Relapse occurred in 6 (32%) patients who had achieved CR. Of the patients who relapsed, 4 patients resumed MPA therapy and were in remission. Among 19 patients, 13 patients attempted pregnancy after CR. All of them underwent ovulation induction or assisted reproductive technology. As a result, 20 pregnancies in 10 (77%) patients and 12 live births in 9 (69%) patients were achieved. Rate of spontaneous abortion was 35% (7/20). MPA therapy can produce a high remission rate, and be considered an effective treatment for patients who wish fertility preservation. Around 70% patients who attempt to pregnancy can have at least one baby by infertility treatments. Because recurrence rate after MPA therapy is high, it may be desirable to aim for early pregnancy by active intervention.
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.
(Summary)
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.
Asuka Takeda, Yuri Yamamoto, Kou Tamura, H. Aoki, Hiroki Noguchi, Saki Minato, Shuhei Kamada, Ryosuke Arakaki, Takashi Kaji and Takeshi Iwasa : Retraction: Self-assembling anticaries mucosal vaccine containing ferritin cage nanostructure and glucan-binding region of S. mutans glucosyltransferase effectively prevents caries formation in rodents (Human Vaccines & Immunotherapeutics, (2017), 13, 10, (2332-2340), 10.1111/jog.16113), The Journal of Obstetrics and Gynaecology Research, Vol.50, No.11, 2164, 2024.
(Summary)
A. Takeda , Y. Yamamoto , K. Tamura , H. Aoki , H. Noguchi , S. Minato , S. Kamada , R. Arakaki , T. Kaji , and T. Iwasa , "Oncologic, Fertility, and Obstetric Outcomes With MPA Therapy in Women with Endometrial Cancer and Atypical Endometrial Hyperplasia," The Journal of Obstetrics and Gynaecology Research 50, no. 4 (2024): 633-638, https://doi.org/10.1111/jog.15872. The above article, published online on 28 December 2023 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Hiroaki Kajiyama; and John Wiley & Sons, Australia, Ltd. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed major conceptual overlap and significant primary data redundancy with a previously published article by an overlapping group of authors. Such publishing practice is against the journal's policy and Wiley's Best Practice Guidelines on Research Integrity and Publishing Ethics.