Cut-off value for anti-Müllerian hormone in the diagnostic criteria for polycystic ovary syndrome in the Japanese population.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Impact of the difference in diagnostic criteria for adolescent polycystic ovary syndrome excluding polycystic ovarian morphology.

AIM: Exclusion of polycystic ovarian morphology (PCOM) from the diagnostic criteria for adolescent polycystic ovary syndrome (PCOS) has been proposed. We analyzed the profiles of adolescent women with suspected PCOS based on the Japan Society of Obstetrics and Gynecology (JSOG) diagnostic and Rotterdam criteria, excluding those with PCOM. METHODS: Thirteen- to twenty-one-year-old women with suspected or confirmed diagnosis of PCOS according to the JSOG and Rotterdam criteria were included in this study. Patient characteristics such as hormone levels and body mass index (BMI) were compared between the groups. Correlations between BMI and testosterone, and BMI and time to diagnosis were also analyzed. RESULTS: Twenty-nine patients were diagnosed with adolescent PCOS according to the JSOG criteria, and 11 patients according to the Rotterdam criteria after excluding the patients fulfilling the PCOM criteria. Serum testosterone levels were significantly higher in adolescents diagnosed with PCOS using the Rotterdam criteria than in those diagnosed using the JSOG criteria (p < 0.001). The obese group had significantly higher testosterone levels and a longer time from menarche to PCOS diagnosis. A positive correlation was observed between BMI and testosterone levels (r = 0.318, p = 0.014). CONCLUSION: Although adolescents with PCOS diagnosed using the Rotterdam criteria exhibited higher testosterone levels, which is a typical characteristic of this condition, the JSOG criteria may be useful for the early diagnosis of adolescent PCOS, including suspected cases. The differences between the two criteria may reflect the natural history of PCOS and its different reproductive and metabolic phenotypes.

Factors related to clearance of the small pelvic cavity during gynecologic laparoscopic surgery.

AIM: To identify factors influencing the Trendelenburg angle required during laparoscopic gynecological surgery. METHODS: Patients who underwent laparoscopic surgery at a single university hospital between May 1, 2019, and March 31, 2021 were enrolled. Data were extracted from the medical records, while magnetic resonance imaging scans and all laparoscopic surgery videos were retrospectively reviewed to assess the presence of the small intestine in the pelvic cavity as well as the adhesions at each site. Groups with and without the small intestine in the pelvic cavity, and those requiring a Trendelenburg angle above or below 13° were compared. RESULTS: In total, 219 patients were examined. The Trendelenburg angle was significantly higher (p = 0.004), while a significant increase in ovarian adhesions was observed (p = 0.033; odds ratio [OR], 2.30; 95% confidence interval [CI], 1.05-5.01) in the group without the presence of the small intestine in the pelvic cavity. Furthermore, the group requiring a Trendelenburg angle of ≥13° had significantly thicker subcutaneous fat (p = 0.044) and more ileal adhesions (p = 0.040, OR, 1.82; 95% CI, 1.03-3.23) than the group with an angle of <13°. CONCLUSION: Cases of ileal adhesions or thick subcutaneous fat are more likely to require a Trendelenburg angle of ≥13°. Therefore, Trendelenburg complications should be considered in this group. In addition, ovarian adhesions make it more difficult to exclude the small intestine from the small pelvic cavity, and may be associated with endometriosis.

Guideline for gynecological practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2023 edition.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Effects of Levothyroxine Treatment on Fertility and Pregnancy Outcomes in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Subclinical hypothyroidism, defined by elevated thyrotropin (TSH) and normal free thyroxine levels, is associated with adverse pregnancy outcomes, including preterm birth, pre-eclampsia, and small for gestational age. Despite the uncertainty regarding the effectiveness of levothyroxine (LT4) treatment on pregnancy outcomes in subclinical hypothyroidism, LT4 is widely administered with a pre-treatment threshold TSH level of 2.5 mU/L. The aim of this study is to investigate the efficacy of periconceptional LT4 treatment for subclinical hypothyroidism, including TSH levels >2.5 mU/L, and identify the characteristics of subclinical hypothyroidism that can benefit from LT4 treatment. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials from inception to February 2023. We analyzed the pooled effects of LT4 on subclinical hypothyroidism before and during pregnancy. The main outcomes before pregnancy were live birth, pregnancy, and miscarriage. The main outcomes during pregnancy were live birth, miscarriage, and preterm birth. We conducted subgroup analyses to compare the effects of LT4 on subclinical hypothyroidism with TSH levels of 2.5-4.0 and >4.0 mU/L. Results: Of the 888 studies identified, 27 full-text articles were screened for eligibility. Five studies on pre-conception treatment with 768 participants and eight studies on treatment during early pregnancy with 2622 participants were analyzed. One of the two studies on pre-conception treatment in subclinical hypothyroidism with TSH >4.0 mU/L had high risk of bias and the other was composed of 64 participants. Pre-conception LT4 treatment had no significant effect in improving rates of live births and pregnancies, or reducing miscarriages (risk ratio [RR], 95% confidence interval): 1.41 (0.84-2.36), 1.73 (0.88-3.39), and 0.46 (0.11-2.00), respectively. LT4 treatment during pregnancy was not significantly associated with higher rates of live births (RR 1.03, 0.98-1.09) nor decreased miscarriage rates (RR 1.01, 0.66-1.53). The effect of LT4 treatment on preterm birth during pregnancy was significantly different depending on the TSH values (p = 0.04); a positive effect was shown in the subclinical hypothyroidism subgroup with TSH >4.0 mU/L (RR 0.47, 0.20-1.10), while no significant effect was observed in the subgroup with TSH 2.5-4.0 mU/L (RR 1.35, 0.79-2.31). Conclusions: Pre-conceptional LT4 treatment for subclinical hypothyroidism does not improve fertility or decrease the incidence of miscarriages. However, further well-designed studies are needed for pre-conceptional treatment, especially in TSH >4.0 mU/L. LT4 treatment during pregnancy had a positive effect on preterm birth; nevertheless, this was only applicable to subclinical hypothyroidism with TSH >4.0 mU/L.

Small extracellular vesicles in follicular fluids for predicting reproductive outcomes in assisted reproductive technology.

BACKGROUND: Assisted reproductive technology accounts for an increasing proportion of infertility treatments, and assessments to predict clinical pregnancy outcomes are desired. Extracellular vesicles exist in follicular fluid, and small non coding RNAs in extracellular vesicles underline the possibility of reflecting pregnancy potential. METHODS: Follicular fluid samples are collected from 20 ovarian follicles of 15 infertile patients undergoing assisted reproductive technology. Extracellular vesicles are isolated by serial centrifugation and small RNA sequencing is performed to investigate the profiles of microRNAs and P-element-induced wimpy testis-interacting RNAs. RESULTS: Small extracellular vesicles with a size range of approximately 100 nm are successfully isolated, and the small non coding RNA profiles of pregnant samples (n = 8) are different from those of non-pregnant samples (n = 12). Fourteen dysregulated small non coding RNAs are selected to identify the independent candidates [mean read count >100, area under the curve >0.8]. Among them, we find that a specific combination of small non coding RNAs (miR-16-2-3p, miR-378a-3p, and miR-483-5p) can predict the pregnant samples more precisely using a receiver operating characteristics curves analysis (area under the curve: 0.96). Furthermore, even in the same patients, the three microRNAs are differentially expressed between pregnant and non-pregnant samples. CONCLUSIONS: Our results demonstrate that small non coding RNAs derived from small extracellular vesicles in follicular fluid can be potential non-invasive biomarkers for predicting pregnancy, leading to their probable application in assisted reproductive technology. Further large-scale studies are required to validate the clinical usefulness of these small non coding RNAs.

Assisted reproductive technologies (ART) are medical procedures used to address infertility. Follicular fluid (FF)is a liquid that surrounds the immature egg cells (oocytes) and provides hormones and nutrients necessary for their maturation and eventual development into embryos. We analyzed genetic components within the FF as a potential predictor of reproductive outcomes following ART. Here, we show that a specific combination of genetic elements produced by the FF in successful pregnancies did not occur in unsuccessful pregnancies. Our findings may help to provide a non-invasive approach to determining reproductive outcomes during ART procedures.

Cervical angle as a possible predictor of abnormal placental position in women with endometriosis.

BACKGROUND: We aimed to examine the effects of endometriosis on the rate of abnormal placentation by comparing the data of pregnant women with and without endometriosis. METHODS: A case-control study was conducted to compare the perinatal outcomes between women with and without endometriosis. In the subgroup analysis, magnetic resonance imaging (MRI) scans of pregnant women with placenta previa were used to measure the cervical angle and its relationship with endometriosis. The cervical angle was measured as the angle between the cervical glands and the line perpendicular to the spinal column in each sagittal MRI section. RESULTS: We retrospectively analyzed data from 3453 cases of singleton deliveries between 2015 and 2019 at two study facilities. Among them, 159 had clinically or surgically confirmed endometriosis. The odds ratio (OR) for abnormal placental position was significantly higher in pregnant women with endometriosis (OR. 2.82; 95% confidence interval [CI], 1.58-5.04). The OR was 3.21 (95% CI, 1.57-6.55) in the endometriosis-surgery group (91 patients) and 2.32 (95% CI, 0.91-5.88) in the non-surgery group (68 patients). Furthermore, 44 women who underwent pelvic MRI after 30 weeks of gestation were included to examine the cervical angle. Then, we compared the date of pregnant women with (n = 6) and without endometriosis (n = 38). Regardless of placental attachment position, the cervical angle was significantly lower in the group with than in the group without a history of endometriosis. CONCLUSION: Pregnant women with a history of endometriosis may have stronger uterine retroversion, which could potentially contribute to abnormal placental positioning.

Assisted reproductive technology in Japan: A summary report for 2021 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology.

Purpose: The Japan Society of Obstetrics and Gynecology (JSOG) registry gathers comprehensive data from registered assisted reproductive technology (ART) facilities in Japan. Herein, we report 2021 ART cycle characteristics and outcomes. Methods: Descriptive statistics were used to summarize and analyze 2021 data. Results: In 2021, 625 ART facilities participated in the registry; 27 facilities did not conduct ART cycles and 598 registered treatment cycles. In total, 498 140 cycles were registered, and there were 69 797 neonates (increases of 10.7% and 15.5%, respectively, from the previous year). The number of freeze-all in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles decreased in 2021; the number of neonates born was 2268 for IVF-embryo transfer (ET) cycles and 2850 for ICSI cycles. Frozen-thawed ET (FET) cycles increased markedly from 2020 (11.2% increase). In 2021, 239 428 FET cycles were conducted, resulting in 87 174 pregnancies and 64 679 neonates. For fresh transfers, the total single ET, singleton pregnancy rate, and singleton live birth rates were 82.7%, 97.0%, and 97.3%; for FET, these rates were 84.9%, 96.9%, and 97.1%. Conclusions: The 2021 Japanese ART registry analysis showed marked increases in both total treatment cycles and live births from the previous year.

Anti-Müllerian hormone for screening, diagnosis, evaluation, and prediction: A systematic review and expert opinions.

AIM: To present evidence-based recommendations for anti-Müllerian hormone (AMH) measurement as an ovarian reserve test. METHODS: A systematic literature search for the clinical utility of AMH was conducted in PubMed from its inception to August 2022 to identify studies, including 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 clinical questions (CQs). RESULTS: A total of 1895 studies were identified and 95 articles were included to establish expert opinions subdivided into general population, infertility treatment, primary ovarian insufficiency, polycystic ovary syndrome, surgery, and oncofertility. We developed 13 CQs and 1 future research question with levels of evidence and recommendations. CONCLUSION: The findings of the current systematic review covered the clinical utility of AMH including its screening, diagnosis, evaluation, and prediction. Although some clinical implications of AMH remain debatable, these expert opinions may help promote a better understanding of AMH and establish its clinical significance.

Psychometric Properties of the Japanese Version of the Edmonton Functional Assessment Tool 2.

CONTEXT: Physical symptoms such as pain and cancer-related fatigue limit physical function and activities of daily living among patients with terminal cancer, which can lead to a decline in quality of life. Therefore, comprehensive functional impairments should be evaluated to determine the progression of the disease and the effectiveness of palliative treatment. OBJECTIVE: To validate the psychometric properties of the Japanese version of the Edmonton Functional Assessment Tool 2 (EFAT2-J). METHODS: We developed a Japanese version of the EFAT-2 in accordance with international guidelines. To verify the reliability and validity of the EFAT2-J, patients were evaluated by a physiotherapist and a nurse separately, and correlations with existing evaluation scales for physical function, physical symptoms, and quality of life were analyzed, respectively. The significance level was set at 5%. RESULTS: Twenty patients participated in the reliability measurement. The average EFAT2-J scores were 7.95 ± 4.12 for physical therapists and 7.20 ± 4.23 for nurses, and the intraclass correlation coefficient was 0.95. The weighted kappa coefficient (κ) for each item was 0.57-1.00. Fifty-five patients participated in the validity measurement. The EFAT2-J showed significant correlations with Eastern Cooperative Oncology Group Performance Status and the Karnofsky Performance Scale, Barthel Index, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care sub-item "physical function." CONCLUSION: These results indicate that the EFAT2-J has robust psychometric properties and is useful for evaluating physical function in patients with terminal cancer, and thus may be an acceptable clinical instrument in research and practice.

Serum miRNA as a predictive biomarker for ovarian reserve after endometrioma-cystectomy.

Ovarian endometrioma (OE) is a common gynecological disease that is often treated with surgery and hormonal treatment. However, ovarian cystectomy can impair the ovarian reserve (OR). Previously, we showed that perioperative administration of dienogest (DNG) is an effective option for OR preservation. However, there were differences in the extent of OR preservation among patients following perioperative DNG treatment. In the current study, we performed a global examination of serum microRNAs (miRNAs) to identify accurate biomarkers that predict post-operative restoration of OR following perioperative DNG treatment. We also sought to identify specific miRNAs related to the anti-Müllerian hormone (AMH). miRNA sequencing was performed on serum samples obtained from twenty-seven patients who received perioperative DNG treatment. Candidate miRNAs were selected by comparing patients whose ORs were restored postoperatively (responder group, n = 7) with those whose ORs were not (non-responder group, n = 7). miR-370-3p and miR-1307-3p were significantly upregulated in the responder group, whereas miR-27b-3p was upregulated in the non-responder group. The pretreatment value of each miRNA could predict DNG responsiveness for OR following ovarian cystectomy (area under the curve [AUC] > 0.8). The quantitative polymerase chain reaction (qPCR) revealed only miR-1307-3p was found to be significantly upregulated in the responder group (P < 0.05). In addition, we identified miR-139-3p, miR-140-3p, and miR-629-5p as AMH-associated miRNAs. The transition of AMH showed a correlation with miR-139-3p (P < 0.05, r = -0.76). The miRNAs identified herein represent potential serum biomarkers of clinical value in predicting OR prior to DNG treatment.

Follicle development and its prediction in patients with primary ovarian insufficiency: Possible treatments and markers to maximize the ability to conceive with residual follicles.

Background: Primary ovarian insufficiency (POI) is characterized by the development of hypergonadotropic hypogonadism before 40 years of age and leads to intractable infertility. Although in vitro fertilization and embryo transfer with donated eggs enables pregnancy, not a few patients desire pregnancy using their oocytes. However, follicular development is rare and unpredictable in patients with POI. Thus, there is a need for treatments that promote the development of residual follicles and methods to accurately predict infrequent ovulation. Methods: This review discusses the effects of various treatments for obtaining eggs from POI patients. Furthermore, this study focused a potential marker for predicting follicular growth in patients with POI. Main Findings: Different treatments such as hormone-replacement therapy, dehydroepiandrosterone supplementation, platelet-rich plasma injection, and in vitro activation have shown varying degrees of effectiveness in retrieving oocytes from patients with POI. To predict follicle development in the cycle, elevated serum estradiol and reduced follicle-stimulating hormone (FSH) levels are important. However, these markers are not always reliable under continuous estradiol-replacement therapy. As a novel marker for predicting follicle growth, serum anti-Müllerian hormone (AMH) levels, measured using the picoAMH enzyme-linked immunosorbent assay, were found to predict follicle growth in patients and the cycle. Conclusion: This review highlights the challenges and available interventions for achieving pregnancy using a patient's oocytes in cases of POI. We believe that a combination of currently available treatments and prediction methods is the best strategy to enable patients with POI to conceive using their own eggs. Although AMH levels may predict follicle growth, further research is necessary to improve the chances of successful follicular development and conception in patients with POI.

Anti-Müllerian hormone beyond an ovarian reserve marker: the relationship with the physiology and pathology in the life-long follicle development.

Anti-Müllerian hormone (AMH), an indirect indicator of the number of remaining follicles, is clinically used as a test for ovarian reserve. Typically, a decline suggests a decrease in the number of remaining follicles in relation to ovarian toxicity caused by interventions, which may implicate fertility. In contrast, serum AMH levels are elevated in patients with polycystic ovary syndrome. AMH is produced primarily in the granulosa cells of the preantral and small antral follicles. Thus it varies in association with folliculogenesis and the establishment and shrinking of the follicle cohort. Ovarian activity during the female half-life, from the embryonic period to menopause, is based on folliculogenesis and maintenance of the follicle cohort, which is influenced by developmental processes, life events, and interventions. AMH trends over a woman's lifetime are associated with in vivo follicular cohort transitions that cannot be observed directly.

Serum leucine-rich α2-glycoprotein as a possible marker for inflammatory status in endometriosis.

Purpose: This study aimed to investigate whether serum leucine-rich α2-glycoprotein (LRG) is a useful diagnostic biomarker for endometriosis, including the evaluation of treatment efficacy and exploration of LRG production in endometriotic lesions. Methods: Forty-three women with endometriomas were compared to 22 women with benign ovarian cysts and 30 women who underwent assisted reproduction as controls. Changes in serum LRG levels were assessed before and after surgery, and during dienogest treatment. LRG expression in endometriotic tissue samples was evaluated using immunoblotting. Results: Serum LRG levels in the endometrioma group (80.0 ± 36.3 µg/mL) were significantly higher than those in the benign ovarian cyst (65.1 ± 27.0 µg/mL, p = 0.0265) and control (57.8 ± 22.3 µg/mL, p = 0.0028) groups. Serum LRG levels after endometrioma surgery were significantly lower than preoperative levels (p = 0.0484). Serum LRG levels consistently decreased during dienogest treatment. LRG expression levels were significantly higher in endometriotic tissues than in the normal endometrium. Conclusion: Serum LRG, possibly derived from local and systemic origins, could be used as a potential biomarker for the diagnosis and treatment of endometriosis.

A cell wall-localized cytokinin/purine riboside nucleosidase is involved in apoplastic cytokinin metabolism in Oryza sativa.

In the final step of cytokinin biosynthesis, the main pathway is the elimination of a ribose-phosphate moiety from the cytokinin nucleotide precursor by phosphoribohydrolase, an enzyme encoded by a gene named LONELY GUY (LOG). This reaction accounts for most of the cytokinin supply needed for regulating plant growth and development. In contrast, the LOG-independent pathway, in which dephosphorylation and deribosylation sequentially occur, is also thought to play a role in cytokinin biosynthesis, but the gene entity and physiological contribution have been elusive. In this study, we profiled the phytohormone content of chromosome segment substitution lines of Oryza sativa and searched for genes affecting the endogenous levels of cytokinin ribosides by quantitative trait loci analysis. Our approach identified a gene encoding an enzyme that catalyzes the deribosylation of cytokinin nucleoside precursors and other purine nucleosides. The cytokinin/purine riboside nucleosidase 1 (CPN1) we identified is a cell wall-localized protein. Loss-of-function mutations (cpn1) were created by inserting a Tos17-retrotransposon that altered the cytokinin composition in seedling shoots and leaf apoplastic fluid. The cpn1 mutation also abolished cytokinin riboside nucleosidase activity in leaf extracts and attenuated the trans-zeatin riboside-responsive expression of cytokinin marker genes. Grain yield of the mutants declined due to altered panicle morphology under field-grown conditions. These results suggest that the cell wall-localized LOG-independent cytokinin activating pathway catalyzed by CPN1 plays a role in cytokinin control of rice growth. Our finding broadens our spatial perspective of the cytokinin metabolic system.

Single coronary artery diagnosed in the perinatal period: A case report.

OBJECTIVE: Having a single coronary artery (SCA) is a rare congenital anomaly in which a single artery arises from the aorta. Although most cases of SCA are asymptomatic and incidental, its effects during the perinatal period remain unknown. Herein, we report a case of pregnant woman with suspected SCA, based on transthoracic echocardiography (TTE) findings. CASE REPORT: A 33-year-old multiparous woman presented with preterm premature rupture of the membrane at 29 weeks gestation. The patient's preoperative electrocardiogram (ECG) showed slight ST changes. TTE showed dilated right coronary artery and hypoplastic left coronary artery. Cesarean section was performed at 30 weeks of gestation due to non-reassuring fetal status. Although poor oxygenation was observed postoperatively, the patient was managed appropriately. She was diagnosed with SCA based on coronary computed tomographic angiography findings one month after delivery. CONCLUSION: Pregnant women with SCA require careful perinatal care.

WUSCHEL-RELATED HOMEOBOX 13 suppresses de novo shoot regeneration via cell fate control of pluripotent callus.

Plants can regenerate their bodies via de novo establishment of shoot apical meristems (SAMs) from pluripotent callus. Only a small fraction of callus cells is eventually specified into SAMs but the molecular mechanisms underlying fate specification remain obscure. The expression of WUSCHEL (WUS) is an early hallmark of SAM fate acquisition. Here, we show that a WUS paralog, WUSCHEL-RELATED HOMEOBOX 13 (WOX13), negatively regulates SAM formation from callus in Arabidopsis thaliana. WOX13 promotes non-meristematic cell fate via transcriptional repression of WUS and other SAM regulators and activation of cell wall modifiers. Our Quartz-Seq2-based single cell transcriptome revealed that WOX13 plays key roles in determining cellular identity of callus cell population. We propose that reciprocal inhibition between WUS and WOX13 mediates critical cell fate determination in pluripotent cell population, which has a major impact on regeneration efficiency.

Fusobacterium infection facilitates the development of endometriosis through the phenotypic transition of endometrial fibroblasts.

Retrograde menstruation is a widely accepted cause of endometriosis. However, not all women who experience retrograde menstruation develop endometriosis, and the mechanisms underlying these observations are not yet understood. Here, we demonstrated a pathogenic role of Fusobacterium in the formation of ovarian endometriosis. In a cohort of women, 64% of patients with endometriosis but <10% of controls were found to have Fusobacterium infiltration in the endometrium. Immunohistochemical and biochemical analyses revealed that activated transforming growth factor-ß (TGF-ß) signaling resulting from Fusobacterium infection of endometrial cells led to the transition from quiescent fibroblasts to transgelin (TAGLN)-positive myofibroblasts, which gained the ability to proliferate, adhere, and migrate in vitro. Fusobacterium inoculation in a syngeneic mouse model of endometriosis resulted in a marked increase in TAGLN-positive myofibroblasts and increased number and weight of endometriotic lesions. Furthermore, antibiotic treatment largely prevented establishment of endometriosis and reduced the number and weight of established endometriotic lesions in the mouse model. Our data support a mechanism for the pathogenesis of endometriosis via Fusobacterium infection and suggest that eradication of this bacterium could be an approach to treat endometriosis.

Decreased lamin A and B1 expression results in nuclear enlargement in serous ovarian carcinoma, whereas lamin A-expressing tumor cells metastasize to lymph nodes.

BACKGROUND: Lamins, located beneath the nuclear membrane, are involved in maintaining nuclear stiffness and morphology. The nuclei of tumor cells are enlarged in serous carcinoma, a histologic subtype of ovarian cancer that is notable for its poor prognosis. The present study investigated the association of lamin A, B1, and B2 expression with nuclear morphology and metastatic route in serous ovarian carcinoma. METHODS: We performed immunohistochemistry for lamins A, B1, and B2 using specimens of patients who underwent surgery for serous ovarian carcinoma in Gunma University Hospital between 2009 and 2020. Following staining, the specimens were scanned using a whole-slide scanner and processed using computer-assisted image analysis. RESULTS: The positivity rates for lamins A and B1 as well as the rank sum of the positivity rates for lamins A, B1, and B2 were negatively correlated with the mean and standard deviation of the nuclear area. Interestingly, the positivity rate for lamin A was significantly higher in metastatic lesions than in primary tumors in cases with lymph node metastasis. DISCUSSION: Previous studies indicated that decreased lamin A led to nuclear enlargement and deformation and that lamin B1 was required to maintain the meshworks of lamins A and B2 to maintain nuclear morphology. The present study findings suggest that decreased lamin A and B1 expression might lead to nuclear enlargement and deformation and raise the possibility that tumor cells maintaining or not losing lamin A expression might metastasize to lymph nodes.

How do plants reprogramme the fate of differentiated cells?

Being able to change cell fate after differentiation highlights the remarkable developmental plasticity of plant cells. Recent studies show that phytohormones, such as auxin and cytokinin, promote cell cycle reactivation, a critical first step to reprogramme mitotically inactive, differentiated cells into organogenic stem cells. Accumulating evidence suggests that wounding provides an additional cue to convert the identity of differentiated cells by promoting the loss of existing cell fate and/or acquisition of new cell fate. Differentiated cells can also alter cell fate without undergoing cell division and in this case, wounding and phytohormones induce master regulators that can directly assign new cell fate.