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.
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.
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.
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
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.
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.
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.
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.
(Summary)
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.
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.
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.
(Summary)
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.