研究者詳細 - 小野政徳

論文 - 小野政徳

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Acute and chronic effects of imeglimin on peripheral circadian clocks in mice

Shi Y., Xu P., Morishige J.I., Yang Y., Iba T., Nagata N., Hosono T., Miyazaki R., Sakane N., Ono M., Fujiwara T., Fujiwara H., Ando H.

Journal of Pharmacological Sciences 160 （ 1 ） 51 - 58 2026年01月

ISSN 1347-8613

OBJECTIVE: This study aimed to investigate the acute and chronic effects of imeglimin, a novel antidiabetic agent, on peripheral circadian clocks in mice under a 12-h/12-h light/dark cycle. METHODS: Female C57BL/6J mice were administered imeglimin either as a single oral dose at Zeitgeber time (ZT) 0 or 12 (acute study) or via a 0.2 % admixture in chow for 4 weeks (chronic study). Clock gene mRNA expression in skeletal muscle and liver was analyzed by quantitative real-time PCR. RESULTS: Acute imeglimin administration at ZT 12 increased the peak mRNA expression of clock genes (Nr1d1 and Dbp in skeletal muscle; Per2 in liver), whereas dosing at ZT 0 decreased Nr1d1 and Dbp in both tissues. In the chronic study, imeglimin decreased the peak expression of Nr1d1 and Dbp in skeletal muscle, while liver rhythms remained unchanged. Nampt and Sirt1 expression was unaffected in either tissue. CONCLUSION: In this study, we demonstrated that imeglimin alters peripheral clock gene expression in healthy mice under both acute bolus administration and chronic mixed-feeding conditions. Further studies are warranted to clarify underlying mechanisms and their physiological relevance.

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Assisted Reproductive Technology in Japan: A Summary Report for 2023 by the Committee on Professional Scientific Conduct and Clinical Ethics of the Japan Society of Obstetrics and Gynecology

Katagiri Y., Jwa S.C., Kuwahara A., Iwasa T., Ono M., Kato K., Kishi H., Kuwabara Y., Taniguchi F., Harada M., Iwase A., Sugino N.

Reproductive Medicine and Biology 25 （ 1 ） e70008 2026年01月

ISSN 14455781

Purpose: To summarize assisted reproductive technology (ART) data for 2023 collected through the Japan Society of Obstetrics and Gynecology registry. Methods and Results: 625 out of 638 registered ART facilities took part in the study, documenting 561 664 treatment cycles and 85 048 newborns (+3.3% and +10.2% increases from 2022). The average age of women undergoing treatment was 37.3 years (standard deviation: 4.8); 205 986 cycles (36.7%) involved women aged ≥ 40 years. Among fresh cycles, oocyte retrieval was performed in 281 665 cycles, including 168 343 freeze-all cycles (59.8%). A total of 2329 pregnancies and 3375 newborns resulted from in vitro fertilization and intracytoplasmic sperm injection cycles, yielding 1772 and 2502 newborns, respectively. The overall rates for single embryo transfer (SET) and singleton delivery were 80.5% and 96.5%. Frozen–thawed embryo transfer accounted for 271 361 cycles, resulting in 109 850 pregnancies and 80 774 newborns, with a SET rate of 84.7% and a singleton delivery rate of 96.3%. Conclusions: In 2023, the second year of insurance coverage, the registry recorded the highest numbers of treatment cycles and newborns. Effective registry systems planned for 2026 will enable comprehensive evaluation of emerging trends in Japanese ART practice.

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Laeverin is Cell-Surface Target for Liquid-Phase Metastasizing Cancer Cells

Kasama H., Sakai Y., Kagami K., Iizuka T., Kanda T., Suzuki T., Kayahashi K., Ono M., Fujiwara T., Yagi S., Inaki N., Matsumoto I., Yamazaki R., Abiko K., Matsumura N., Hattori A., Daikoku T., Fujiwara H.

Advanced Science 12 （ 47 ） 2025年12月

Laeverin (LVRN) is a cell-surface immunoregulatory factor that is specifically expressed in embryo-derived extravillous trophoblast, which invades maternal spiral arteries without immune rejection during human placentation. Here, it is found that various epithelial cancer cell lines upregulated LVRN expression in association with the expression of POU5F1 after spheroid formation under floating conditions. Immunohistochemically, LVRN expression is detected in the lesions of vascular, lymphatic, and peritoneal invasion of ovarian, cervical, endometrial, breast, and lung cancers. LVRN-positive circulating tumor cells are also identified in the blood of uterine cervical and endometrial cancers, showing that LVRN expression is induced in cancer cells in the distant metastatic phase. Monomethylauristatin E-conjugated anti-LVRN antibody induced cell death in ovarian cancer-derived cell lines in the liquid phase in vitro and inhibited their peritoneal dissemination in nude mice in vivo. These findings indicate that LVRN is a unique and promising cell-surface target molecule for liquid-phase metastasizing cancer cells.

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Novel Subtype Classification of Diffuse Uterine Leiomyomatosis Based on a Nationwide Survey in Japan

Ishikawa H., Asano R., Ono M., Kitade M., Kusumi M., Tsuji S., Nakamura T., Maekawa R., Goto Y., Takada A., Koga K.

Journal of Obstetrics and Gynaecology Research 51 （ 12 ） 2025年12月

ISSN 13418076

Aim: Diffuse uterine leiomyomatosis (DUL) is characterized by numerous uterine leiomyomas within and diffusely replacing the myometrium. However, because of its rarity, the prevalence, diagnostic criteria, and standard treatment for patients with DUL who wish to preserve their fertility remain unknown. This study aimed to clarify the current status of the diagnosis of DUL in Japan. Methods: We conducted a web-based survey targeting 1080 Obstetrics and Gynecology training institutions registered with the Japanese Medical Specialty Board. We asked them whether they had treated patients with DUL over the past 10 years (2013–2022). We obtained magnetic resonance imaging (MRI) scans from institutions that reported clinical experience with DUL, and conducted a central review to determine whether each case was consistent with DUL. We also investigated whether DUL could be classified into subtypes. Results: Responses were obtained from 428 institutions, of which 128 reported clinical experience with DUL or DUL-like multiple uterine leiomyomas, totaling 653 cases. MRI scans from 408 cases were centrally reviewed by a subcommittee, and 307 cases were confirmed as DUL. Based on the imaging characteristics, DUL was classified into three subtypes: total replacement, myometrial replacement, and submucosal-dominant. Conclusions: This survey revealed that 653 cases of DUL or DUL-like multiple uterine leiomyomas were managed over a 10-year period in Japan. Based on a central review of MRI scans, DUL can be classified into three distinct subtypes. Given the differences between these subtypes, treatment approaches for patients wishing to preserve fertility may vary, highlighting the need for further investigation.

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Modified screening of MYC promotor region elements using the CRISPR library in ovarian cancer

Yamamoto A., Tanaka Y., Ishibashi S., Ikeda M., Sugita K., Ono M., Nishi H., Kurata M.

Journal of Ovarian Research 18 （ 1 ） 2025年12月

Ovarian cancer remains one of the most lethal gynecological malignancies owing to its high recurrence rate and chemotherapeutic resistance. MYC is a well-known proto-oncogene that is frequently amplified in ovarian cancer and has been implicated in drug resistance. Previously, we established a new promoter–reporter system combined with a CRISPR activation library to identify unknown MYC regulators, and M1AP was identified as a novel MYC regulator. However, considering the insufficient explanation for the absence of guide RNA (gRNA) of MYC, this present study explored methods to prevent the gRNA of MYC itself from binding. This study first modified the promoter–reporter vector to improve its quality, then conducted CRISPR screening and analyzed candidate genes as MYC promoter regulators using next-generation sequencing in OVSAHO ovarian cancer cells. Eighty-six genes had ≥ 1000 reads, and Pearson’s correlation coefficient analysis was performed on the cBioPortal of the Cancer Genomics database. Fourteen genes were identified as candidate MYC regulators with positive and significant correlations with MYC. Seven genes, including CYP4v2, ASPH, ANP32D, PCED1A, ABI1, FUZ, and HOOK2, demonstrated significantly higher luciferase activity than the control genes. Four genes, including ABI1, PCED1A, HOOK2, and CYP4v2, activated the MYC promoter, which showed over twofold higher activity than the control when overexpressed using a vector. In conclusion, four genes that activate MYC promoters were identified in an ovarian cancer cell line using the CRISPR library system with a modified promoter–reporter tool. These results will prove helpful in the development of novel treatment strategies for ovarian cancer.

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Role of Transcription Factor, LIM Homeobox 9 (LHX9) in Inflammatory Response by PGE2 and Thrombin in SERPINA1-Silencing Endometrial Stromal Cells

Kusama K., Ashihara M., Okita M., Yoshida K., Suzuki M., Suzuki K., Hosokawa R., Yoshie M., Kojima J., Mizuno Y., Ono M., Nishi H., Kajihara T., Tamura K.

Molecular Reproduction and Development 92 （ 8 ） 2025年08月

ISSN 1040452X

Endometriosis is hypothesized to result from retrograde menstruation where cell debris including endometrial stromal cells (ESCs) travel through the fallopian tubes. This chronic inflammatory disease is characterized by inflammatory and fibrotic endometrial tissue. We have previously observed reduced expression of the anti-inflammatory factor SERPINA1 in endometriosis-like lesions in a mouse model implanted with human ESCs. Additionally, pro-inflammatory factors present in peritoneal hemorrhage exacerbated inflammation in these grafts, partly through prostaglandin (PG) E2 and thrombin. However, it remains unclear whether the reduction of SERPINA1, in combination with PGE2 and thrombin, synergistically influences the expression of inflammatory factors in endometriosis lesions and the underlying mechanisms. We analyzed RNA sequencing data from ESCs treated with SERPINA1 siRNA and PGE2/thrombin, comparing them to data sets derived from ESCs subjected to either SERPINA1 knockdown or PGE2/thrombin treatment. Comparative analysis identified 49 transcripts that were upregulated under both conditions and enriched for transcription regulatory genes, including SNAI1, HDAC5, PBX1, SOX4, EPAS1, LHX9, and MAFK. Silencing SNAI1, HDAC5, SOX4, EPAS1, or LHX9 suppressed IL6, CXCL8, and IL1B expression, which had been upregulated by SERPINA1 siRNA and PGE2/thrombin. Among these genes, LHX9 expression was significantly elevated in ectopic lesions, predominantly localized to stromal and glandular epithelial cells, with more pronounced expression during the secretory phase. LHX9 levels were also increased in endometriotic lesions compared to the normal endometrium. In conclusion, reduced SERPINA1 expression in ectopic ESCs, combined with PGE2/thrombin, induces inflammatory cytokine expression linked to LHX9. Pharmacological targeting of LHX9 may present a promising therapeutic strategy for mitigating chronic inflammation in endometriotic lesions.

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Cumulative ongoing pregnancy and live birth rates after assisted reproduction among women with diminished ovarian reserve: A multi-institutional retrospective cohort study

Kobayashi M., Asada Y., Sugishita Y., Osuka S., Kitajima M., Kawamura K., Shirasawa H., Tsuzuki T., Yamada M., Huang H., Jwa S.C., Suzuki T., Kanasaki H., Kuroda K., Ono M., Katagiri Y., Noguchi H., Fukui A., Wada-Hiraike O., Masaki K., Kitahara Y., Iwase A.

Journal of Obstetrics and Gynaecology Research 51 （ 6 ） e16336 2025年06月

ISSN 13418076

Aim: To examine the cumulative ongoing pregnancy/live birth rate per patient by encompassing all embryo transfer (ET) cycles associated with a single oocyte retrieval cycle among women with diminished ovarian reserve (DOR), and to investigate whether serum anti-Müllerian hormone (AMH) levels can predict a live birth success. Methods: This multi-institutional retrospective cohort study included infertile women with DOR (AMH <1.1 ng/mL) who began their first cycle of in vitro fertilization and/or intracytoplasmic sperm injection between January and December 2021. Outcomes using the retrieved embryos were evaluated for up to four ET cycles. Results: Of 606 patients, 113 did not undergo ET. A total of 605 ET cycles were analyzed. Clinical pregnancy and ongoing pregnancy/live birth rates per ET cycle were significantly dependent on age, not AMH levels. Ongoing pregnancy/live birth rates per patient increased significantly with higher AMH levels. A significant difference in the cumulative ongoing pregnancy/live birth rate was observed depending on whether cases with no remaining embryos were included among the censored cases. Conclusion: Assisted reproductive technology (ART) outcomes per ET cycle in women with DOR were similar to those reported in the Japanese ART registry without distinguishing DOR. The greater the number of good-quality embryos that can be frozen, the higher the expected cumulative live birth rate.

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BMAL1 Regulates Collagen Production in the Myometrium and Leiomyomas

Dai Y., Ono M., Suzuki T., Hayashi S., Kojima J., Sasaki T., Fujiwara T., Daikoku T., Terakawa J., Maida Y., Ando H., Fujiwara H., Kuji N., Nishi H.

Reproductive Sciences 32 （ 4 ） 1115 - 1128 2025年04月

ISSN 19337191

Infertility and reproductive issues are commonly observed in animals with clock abnormalities. Substantial rodent data is available; however, relatively few studies have investigated the connection between fertility and clock abnormalities in humans. Therefore, this study aimed to analyze the expression of circadian clock genes and their impact on genes involved in collagen production in the human myometrium and leiomyomas (LM). The relationship between the expression of brain and muscle aryl-hydrocarbon-receptor-nuclear-translocator (Arnt)-like protein-1 (BMAL1) and the genes responsible for collagen synthesis in the human MM and LMs were investigated. Human MM and LM tissues were collected for analysis from patients who underwent hysterectomy analysis. Immunohistochemical analysis, cell culturing, immunofluorescence, small interfering RNA transfection, reverse transcription quantitative real-time polymerase chain reaction, scratch wound assays, and transwell assays were employed to gain a comprehensive understanding of the cellular and molecular processes. A correlation was found between BMAL1 expression and genes regulating collagen synthesis in primary cultures of human MM and LM cells. Moreover, the inhibition of BMAL1 differentially increased the migration and invasion of MM and LM cells. This work discloses the role of BMAL1 in collagen production in primary cultures of human MM and LM cells, offering insight into clock gene involvement in both normal and pathological uterine conditions. Furthermore, this study highlights the crucial role of BMAL1 in collagen synthesis in human MM and LM cells, underscoring the significance of BMAL1 in the regulation of reproductive physiology. These results suggest that BMAL1 might be a useful target molecule for anti-LM therapy.

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Clinical effectiveness of the subcutaneous steel wire-lifting method with gasless laparoscopic myomectomy for fibroids

Sakai Y., Sasaki T., Ono M., Hayashi S., Yamanaka Z., Ono M., Yamamoto A., Nishi H.

Asian Journal of Surgery 48 （ 1 ） 370 - 376 2025年01月

ISSN 10159584

Background/objective: Laparoscopic myomectomy (LM) is primarily conducted using the pneumoperitoneum method, with only few LMs performed using the gasless method (GLM). We aimed to assess the feasibility of GLM. Methods: This retrospective chart review was performed in a university-affiliated hospital. We included 1301 patients who underwent GLM with the subcutaneous steel wire-lifting method (GLMS) between 2008 and 2021. Results: A total of 6287 fibroids were removed (nodes per patient: 4.83 ± 4.51). Systematic reviews showed that compared with conventional LM, GLMS had longer operation time, greater number and larger size of fibroids removed, and lower intraoperative blood loss. The rates of severe perioperative complications, homologous blood transfusion, and open conversion were acceptable at 0.8 %, 0.5 %, and 0.3 %, respectively. Operation time, weight of surgical specimen, body mass index (BMI), and the maximum diameter of fibroids removed were important predictors of higher risk, including massive surgical bleeding. The prediction model of massive surgical bleeding showed a relatively good out-of-bag estimate of error rate of 8.6 %, with a high negative predictive value, albeit a low positive predictive value, making it unsuitable for real-world clinical applications. Conclusions: GLMS is an excellent procedure that combines safety, proficiency, and economic efficiency for fibroid removal, except in patients with severe obesity. Beyond the cost–benefit perspective, GLMS appears well-suited to countries with low average BMI, such as Japan, East-Asian countries, and LMICs in Africa.

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Conception After Chemotherapy for Intraplacental Choriocarcinoma: Favorable 5-Year Follow-Up of the Mother and Child

Suzuki T., Ono M., Kojima J., Imai Y., Nagai T., Suzuki A., Kuji N., Nishi H.

American Journal of Case Reports 26 2025年

Objective: Rare disease Background: Intraplacental choriocarcinoma (IC) is a rare subtype of gestational choriocarcinoma that can be associated with placental hemorrhage and metastases to the mother and fetus. Chemotherapy can be effective in cases of placental localization and may not adversely affect fertility. This report describes a 32-year-old woman who conceived 10 months after chemotherapy for IC and achieved successful term delivery of that pregnancy. Case Report: A 32-year-old woman delivered her first child by vacuum extraction due to weak labor and fetal distress. The newborn presented with severe anemia, as well as elevated alpha-fetoprotein and fetal hemoglobin levels, suggesting fetomaternal hemorrhage. Placental histopathology revealed IC. Postpartum elevation of human chorionic gonadotropin levels prompted EMA-CO (etoposide, methotrexate, actinomycin D/cyclophosphamide, vincristine) chemotherapy; 7 treatment courses were completed without side effects or metastasis. Ten months after completion of chemotherapy, the patient spontaneously conceived. She subsequently delivered a healthy boy at 38+5 weeks of gestation; placental examination did not reveal malignancy. During the 5-year follow-up period, both children developed normally, and no maternal recurrence or metastasis was observed. Conclusions: This report describes a case of postnatal diagnosis of IC via placental histopathology, followed by successful treatment and subsequent pregnancy within 1 year after chemotherapy completion. The findings highlight the importance of accurate diagnosis and appropriate management of IC; they support previous observations that chemotherapy does not preclude future successful pregnancies. Additionally, the report underscores the clinical challenges of IC, its implications for future pregnancies, and the need for long-term follow-up concerning both mother and child.

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Influence of lifestyle and the circadian clock on reproduction.

Ono M, Dai Y, Fujiwara T, Fujiwara H, Daikoku T, Ando H, Kuji N, Nishi H

Reproductive medicine and biology 24 （ 1 ） e12641 2025年

ISSN 1445-5781

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Out-of-pocket fertility preservation expenses: data from a Japanese nationwide multicenter survey

Ono M., Takai Y., Harada M., Horie A., Dai Y., Kikuchi E., Miyachi M., Yamamoto T., Fujii N., Kajiyama H., Manabe A., Yasuoka T., Katsuragi S., Mekaru K., Maezawa T., Horage Y., Kataoka S., Nakayama R., Nakajima T.E., Kimura F., Shimizu C., Sugimoto K., Takae S., Yumura Y., Nishi H., Furui T., Morishige K.I., Watanabe C., Osuga Y., Suzuki N.

International Journal of Clinical Oncology 29 （ 12 ） 1959 - 1966 2024年12月

ISSN 13419625

Background: The expenses related to fertility preservation or subsequent assisted reproductive treatments are significant for adolescents and young adult patients in Japan’s current healthcare system. With fertility preservation becoming more widespread in developed countries, it is expected that these costs will be covered by insurance or subsidies. It is critical for patients, healthcare providers, and the government to know the costs that patients will be responsible for. In Japan, the costs of fertility preservation and subsequent assisted reproductive technology are not covered by insurance, but patients can apply for subsidies from the local and central governments if certain conditions are met. Presently, the above-mentioned costs, as well as the amount paid by the patient, vary by facility. Therefore, it is essential to ensure patients’ continued access to necessary medical care despite the associated costs. Methods: In this study, questionnaires were mailed to 186 certified fertility preservation facilities in Japan to assess patients who had undergone fertility preservation or assisted reproduction. The questionnaires were sent between October 27, 2023 and March 31, 2024, with 140 of the 186 facilities responding (response rate: 75.3%). Results: Our findings show that approximately one-third of the costs was borne by the patients. Conclusion: Given these circumstances, sustainable pricing and insurance coverage are necessary for both patients and facilities.

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Exenatide administration time-dependently affects the hepatic circadian clock through glucagon-like peptide-1 receptors in the central nervous system

Xu P., Morishige J.i., Jing Z., Nagata N., Shi Y., Iba T., Daikoku T., Ono M., Maida Y., Fujiwara T., Fujiwara H., Ando H.

Biochemical Pharmacology 230 2024年12月

ISSN 00062952

Accumulating evidence indicates that disruption of the circadian clock contributes to the development of lifestyle-related diseases. We have previously shown that exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, can strongly affect the molecular clocks in the peripheral tissues. This study aimed to investigate the effects of its dosing time and the central nervous system-specific GLP-1 receptor knockdown (GLP1RKD) on the hepatic clock in mice treated with exenatide. Male C57BL/6J and GLP1RKD mice were housed under a 12-h/12-h light/dark cycle, and feeding was restricted to either the light period (L-TRF) or the first 4 h in the dark period (D-TRF). In parallel, exenatide was administered 4–5 times, once daily either at the beginning of the dark (ZT 12) or light period (ZT 0), and we assessed the mRNA expression rhythms of clock genes in the liver thereafter. Exenatide administration at ZT 12 counteracted the phase shift effect of the L-TRF on the hepatic clock of wild-type mice, whereas the dosing at ZT 0 enhanced its effect. However, exenatide did not influence the phase of the hepatic clock under D-TRF regardless of the dosing time. The effect of exenatide in wild-type mice weakened in GLP1RKD mice. These results showed that exenatide dosing time-dependently affects the hepatic circadian clock through the central GLP-1 system. Exenatide administration at the beginning of the active period (i.e., in the morning for humans) might prevent disruption of the peripheral clocks caused by irregular eating habits.

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Comparison of the Effects of Inappropriate Meal Timing-Induced and Genetic Models of Circadian Clock Disruption on Uterine mRNA Expression Profiles

Chen Y., Hosono T., Ono M., Daikoku T., Toyoda N., Nomura S., Kagami K., Orisaka S., Horike S.i., Shi Y., Xu P., Morishige J.i., Fujiwara T., Fujiwara H., Ando H.

Journal of Nutrition 154 （ 12 ） 3718 - 3725 2024年12月

ISSN 00223166

Background: Accumulating evidence reveals that inappropriate meal timing contributes to the development of lifestyle-related diseases. An underlying mechanism is thought to be the disruption of the intracellular circadian clock in various tissues based on observations in both systemic and tissue-specific clock gene-deficient mice. However, whether the effects of conditional clock gene knockout are comparable to those of inappropriate meal timing remains unclear. Objectives: This study aimed to compare the effects of a recently developed 28-h feeding cycle model with those of a core clock gene Bmal1 uterine conditional knockout (Bmal1 cKO) model on uterine mRNA expression profiles. Methods: The models were generated by subjecting C57BL/6J mice to an 8-h/20-h feeding/fasting cycle for 2 wk and crossing Bmal1-floxed mice with PR-Cre mice. Microarray analyses were conducted using uterine samples obtained at the beginning of the dark and light periods. Results: The analyses identified 516 and 346, significantly 4-fold and 2-fold, up- or downregulated genes in the 28-h feeding cycle and Bmal1 cKO groups, respectively, compared with each control group. Among these genes, only 7 (1.4%) and 63 (18.2%) were significantly up- or downregulated in the other model. Moreover, most (n = 44, 62.9%) of these genes were oppositely regulated. These findings were confirmed by gene set enrichment analyses. Conclusions: This study reveals that a 28-h feeding cycle and Bmal1 cKO differently affect gene expression profiles and highlights the need for considering this difference to assess the pathophysiology of diseases associated with inappropriate meal timing.

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Androgen-responsive FOXP4 is a target for endometrial carcinoma

Kayahashi K., Hasan M., Khatun A., Kohno S., Terakawa J., Horike S.I., Toyoda N., Matsuoka A., Iizuka T., Obata T., Ono M., Mizumoto Y., Takahashi C., Fujiwara H., Daikoku T.

Communications Biology 7 （ 1 ） 2024年12月

Although low estrogen is considered to suppress uterine endometrial carcinoma, the most cases occur in the postmenopausal stage. After menopause, the production of androgen level also declines. Therefore, to resolve the above enigma, we hypothesize that the postmenopausal decline of androgen is a trigger of its progression. In the present study, to validate this hypothesis, we examine the pathological roles of androgen/AR by analyzing clinical data, culturing endometrioid cancer cell lines, and using murine models. Clinical data show that androgen receptor (AR) expression and serum dihydrotestosterone (DHT) are associated with lower disease-free survival (DFS). DHT suppresses malignant behaviors in AR-transfected human endometrial cancer cells (ECC). In ovariectomized Ptenff/PRcre/+ mice, DHT decreases the proliferation of spontaneously developed murine ECC. In AR-transfected human ECC and Ptenff/PRcre/+ mice, DHT suppresses FOXP4 expression. FOXP4-overexpressed human ECC increases, while FOXP4-knocked-down ECC shows decreased malignant behaviors. DHT/AR-mediated ECC suppression is restored by FOXP4 overexpression. The high FOXP4 expression is significantly correlated with low postoperative DFS. These findings indicate that the androgen/AR system suppresses the malignant activity of endometrial carcinoma and that downstream FOXP4 is another target molecule. These findings will also impact developments in clinical approaches to elderly health.

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Impact of daily breakfast intake on the outcomes of assisted reproductive technology procedures

Ono M., Hayashizaki Y., Orihara S., Kitamizu M., Hamada C., Yamaguchi M., Kikuchi T., Kawamura T., Yamanaka A., Ueno K., Kojima J., Fujiwara T., Daikoku T., Maida Y., Ando H., Fujiwara H., Oshima K., Kuji N., Nishi H.

Nutrition 127 2024年11月

ISSN 08999007

Objective: To assess the relationship between meal consumption frequency and assisted reproductive technology (ART) outcomes among female patients with infertility. Research Methods & Procedures: This cohort study was conducted from February 2022 to January 2024 at Tokyo Medical University Hospital. Overall, 101 female patients with infertility issues and without a history of stroke, heart disease, cancer, or type 1 or type 2 diabetes were enrolled in this study. The factors extracted from the questionnaire included demographic information, meal consumption frequency before ART and at 20 years of age, smoking status, and alcohol consumption status. Data on other factors, including age, body mass index, anti-Müllerian hormone level, and parity history, were collected from medical records. The assessed clinical outcomes included number of transplanted embryos, clinical pregnancies, ongoing pregnancies, live births, and miscarriages. Results: After adjusting for potential confounding factors, including age, smoking status, alcohol consumption status, body mass index, anti-Müllerian hormone level, and parity history, a multivariate analysis of ART outcomes was performed. Patients were categorized into groups based on the frequency of weekly consumption of breakfast, lunch, and dinner. Patients who consumed breakfast 6–7 times a week were significantly more likely to have higher rates of live birth and lower rates of miscarriage in pregnancies conceived through ART. Conclusions: Consumption of breakfast 6–7 times a week before ART was associated with increased success rates following ART. This highlights the potential importance of regular breakfast consumption for optimizing ART outcomes.

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A case of Herlyn–Werner–Wunderlich syndrome with exacerbation of hematometra after adnexectomy

Hayashi S., Ono M., Sagisaka M., Mimura T., Kojima J., Ono M., Sasaki T., Yamamoto A., Nishi H.

Asian Journal of Endoscopic Surgery 17 （ 4 ） 2024年10月

ISSN 17585902

A 27-year-old nulliparous woman presented with a feeling of fullness in the lower abdomen and abdominal pain. A left ovarian tumor, uterus didelphys, left renal agenesis, and left vaginal atresia were observed on imaging. The ovarian tumor was presumed to have caused the abdominal pain, and an abdominal left adnexectomy was performed. After 3 months, she reported severe lower abdominal pain during menstruation. Transvaginal ultrasonography revealed uterine enlargement. After 17 days, the patient presented with abdominal pain and fever. She was diagnosed with peritonitis due to infection and left uterine hematometra. Because she did not improve with antibiotic treatment, left laparoscopic hysterectomy was performed. Subsequently, she did not experience the lower abdominal pain. Appropriate diagnosis and treatment based on the morphology of the reproductive tract and symptoms must be considered in patients with Herlyn–Werner–Wunderlich syndrome. Treatment must permit the outflow of menstrual blood.

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Diagnosis of abnormal uterine bleeding based on the FIGO classification: A systematic review and expert opinions

Kitahara Y., Hiraike O., Ishikawa H., Kugu K., Takai Y., Yoshino O., Ono M., Maekawa R., Ota I., Iwase A.

Journal of Obstetrics and Gynaecology Research 50 （ 10 ） 1785 - 1794 2024年10月

ISSN 13418076

Aim: To present evidence- and consensus-based recommendations for the diagnosis abnormal uterine bleeding. Methods: A literature search for the diagnosis of abnormal uterine bleeding was systematically conducted in PubMed from its inception to May 2024 to identify meta-analyses, reviews, randomized controlled trials, and clinical trials, followed by an additional systematic search using keywords. Based on this evidence, an expert panel developed background, clinical, and future research questions. Results: Based on a systematic search and the collected evidence, we developed five background questions, three clinical questions, and one future research question, with recommendations and/or statements. Evidence and recommendations are provided for clinical questions. Additionally, we developed a flowchart for diagnosis showing the steps of the examinations to be performed. Conclusion: The flowchart and nine recommendations/statements specify an efficient diagnostic procedure to differentiate abnormal causative diseases of uterine bleeding optimized for actual Japanese situations.

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A nationwide survey of diagnostic procedures for abnormal uterine bleeding in Japan

Kitahara Y., Hiraike O., Ishikawa H., Kugu K., Takai Y., Yoshino O., Ono M., Maekawa R., Ota I., Iwase A.

Journal of Obstetrics and Gynaecology Research 50 （ 9 ） 1675 - 1680 2024年09月

ISSN 13418076

Aim: To clarify the diagnostic process of the causative disease of abnormal uterine bleeding (AUB) in Japan according to the International Federation of Gynecology and Obstetrics AUB diagnostic system. Methods: Patients diagnosed with AUB were included in a nationwide survey of AUB conducted during any 2-week period between December 2019 and January 2020. The second survey included information on patient background, AUB symptoms, examinations for diagnosing AUB, the order in which they were performed, and the causative diseases of AUB. Results: Correspondence analysis showed an association between hormonal testing, hysterosalpingography, and magnetic resonance imaging (MRI) in patients with amenorrhea, and heavy menstrual bleeding was strongly correlated with various examinations, such as coagulation tests, pelvic MRI, and endometrial cytology or biopsy. The results also indicated that each AUB causative disease can be diagnosed based on a specific examination profile. Conclusion: We clarified the process of diagnosing the causative disease of AUB in our country and determined that it was mainly diagnosed by imaging and pathological examination in cases of structural disease. The high rate of AUB-E and the low rate of AUB-C are possibly associated with specific examination trends in Japan. The results of this study will be useful for the development of a standard protocol for AUB diagnosis in our country.

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Survey on the implementation status and reproductive outcomes of oocyte and ovarian tissue cryopreservation in Japan: Historical comparison with nationwide surveys

Takae S., Harada M., Nakamura K., Furuyama S., Ono M., Osuga Y., Suzuki N.

Journal of Obstetrics and Gynaecology Research 50 （ 4 ） 709 - 718 2024年04月

ISSN 13418076

Purpose: To clarify the reproductive outcomes of fertility preservation (FP) treatment. Methods: We conducted a mailed-in questionnaire survey at institutions certified by the Japan Society of Obstetrics and Gynecology to investigate the number of oocyte cryopreservations (OC) and ovarian tissue cryopreservations (OTC) performed from December 2016 to the end of 2020. And, we conducted a detailed investigation of cases in which frozen specimens were used during the investigation period, and made historical comparisons with previous nationwide studies. Results: Responses were received from 114 out of 150 facilities (response rate: 76.0%) for OC and 43 out of 51 for OTC (response rate: 84.3%). Breast cancer was the most common disease among patients whose FP specimens were used. During the study period, 1237 OCs and 198 OTCs were performed. In addition, 57 cycles of embryo transfer (ET) using cryopreserved oocytes and 12 cases of ovarian tissue transplantation (OTT) were performed. The mean age of patients who underwent ET using cryopreserved oocytes was 34.8 (±5.8) years, with a median age of 36 years. The pregnancy rate per ET using cryopreserved oocytes was 26.3% and the live birth rate (LBR) was 17.5%. Further, the LBR per patient was 43.3%, and the pregnancy rate following OTTs was 33.3%. Also, controlled ovarian stimulation using the random start method or the combination of aromatase inhibitors had no effect on pregnancy outcome. Conclusion: Implementation of both OCs and OTCs have markedly increased over time in Japan, with comparable reproductive outcomes as other reports.

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