Eiji Kondoh

Pregnancy is accompanied by profound endocrine remodeling, yet the mechanisms by which maternal hormonal signals establish long-term tissue homeostasis remain largely unknown. Here we identify maternal progesterone signaling as a developmental cue that establishes lifelong oral homeostasis through a hormone–lipid–microbiome axis. We show that the membrane progesterone receptor mPRδ is selectively expressed in the developing and maternal submandibular glands, where it mediates non-genomic progesterone signaling to promote epithelial differentiation by driving the selective mobilization of docosahexaenoic acid (DHA). Loss of this pathway disrupts salivary gland maturation, reshapes the oral microbial ecosystem through the selective expansion of Pasteurellaceae, and causes local inflammation as well as systemic metabolic dysfunction. Mechanistically, antibiotic treatment abolishes these phenotypes, whereas transfer of the oral microbiota recapitulates disease, demonstrating that developmental defects in the host are translated into long-term pathology through the oral microbiome. Remarkably, maternal—but not adult—DHA supplementation restores salivary gland development and microbial homeostasis and prevents adult disease phenotypes, identifying a critical developmental window during which oral homeostasis is durably established. Collectively, these findings reveal a previously unrecognized maternal endocrine mechanism that establishes lifelong host–microbiome homeostasis and identify developmental programming as a fundamental principle linking maternal physiology to adult health.

Oligometastases of uterine cervical cancer, particularly in the lungs, present a challenging clinical scenario, as clear guidelines for adjuvant therapy following metastasectomy are lacking. This study investigated whether postoperative chemotherapy is necessary for patients with completely resected pulmonary oligometastases. This multicenter retrospective study included 40 patients with recurrent cervical cancer and pulmonary oligometastasis who underwent complete metastasectomy between April 2005 and December 2018. Patients were divided into a chemotherapy group (n = 14) and a chemotherapy-free group (n = 26). We compared the 5-year overall survival and progression-free survival from metastasectomy and evaluated the prognostic factors using univariate and multivariate analyses. The 5-year progression-free survival rates were 64.3% (95% CI, 34.3–83.3%) and 53.0% (95% CI, 32.2–70.1%) in the chemotherapy and chemotherapy-free groups, while the 5-year overall survival rates were 77.9% (95% CI, 45.9–92.3%) and 84.9% (95% CI, 64.0–93.9%), respectively. A total of eight deaths occurred during follow-up, including three in the chemotherapy group and five in the chemotherapy-free group. No statistically significant differences in progression-free or overall survival were observed between the two groups. However, the small sample size, limited number of survival events, and potential selection bias preclude definitive conclusions regarding the benefit of postoperative chemotherapy. Further large-scale, multicenter studies are warranted to clarify its role following complete resection of pulmonary oligometastases from cervical cancer.

Electrohysterography (EHG) is an advanced, noninvasive technique for characterizing myometrial activity from the maternal abdominal surface. Despite its clinical relevance, the adoption of EHG in wearable systems is hindered by variability in electrode configurations and a lack of integrated system design. A PRISMA 2020-based systematic review of publications from September 1997 to January 2026 was conducted using IEEE Xplore, PubMed, Semantic Scholar, ScienceDirect, SpringerLink, MDPI, IOP, and Frontiers, supplemented by Crossref searches via Publish or Perish and manual citation tracking. Of the 1084 records identified, 91 publications were included in the evidence synthesis. The analysis examined electrode configurations, wearable design, and measurement methodologies, focusing on the effects of electrode density and placement on signal quality and clinical usability. The reviewed literature indicates that configurations employing approximately 8–16 electrodes represent a practical range for balancing spatial characterization and clinical usability. However, the findings reveal persistent challenges related to the limited integration of electrode design, signal acquisition, and analytical methods. This evidence underscores the need for an integrated approach that considers flexible electrode interfaces, standardized electrode configurations, and adaptive signal processing techniques. By aligning technological improvements with clinical requirements, this study identifies practical considerations for developing wearable maternal–fetal monitoring systems.

Progesterone governs the establishment and maintenance of pregnancy in ruminants, acting through the nuclear progesterone receptor (PGR) and, potentially, through membrane progesterone receptors (mPRs) of the PAQR family. The cellular distribution of mPRs in ruminant reproductive tissues, however, remains undefined. We generated and validated rabbit polyclonal antibodies against the intracellular C-terminal peptides of bovine PAQR6 (mPRδ) and PAQR8 (mPRβ), and used them, with quantitative PCR of the uterus and conceptus, to map these receptors in the ovine uterus and conceptus and in the bovine ovary. Both antisera showed high ELISA titer against their immunizing peptides, negligible preimmune reactivity, and complete loss of tissue signal after peptide pre-absorption. By qPCR, PAQR6 , PAQR8 and PGR transcript levels did not change significantly across the peri-implantation period in either the conceptus or the endometrium; in contrast, the progesterone-responsive gene ZBTB16 increased markedly in the conceptus (up to ∼45-fold by day 21, p < 0.05 at days 17, 19 and 21), whereas FKBP5 showed a numerical increase without reaching statistical significance. Both genes remained relatively stable in the endometrium, indicating conceptus-specific changes in progesterone-responsive gene expression. At the protein level, PAQR6 and PAQR8 localized to the luminal and glandular epithelium of the endometrium across the cycle and early pregnancy, and to follicular (granulosa) and luteal cells of the ovary. Dual immunofluorescence in the ovine endometrium showed that both PAQR6 and PAQR8 are enriched at the apical surface of the luminal epithelium and are spatially distinct from the basolateral adherens-junction marker E-cadherin. These results provide a protein-level map of PAQR6 and PAQR8 in the ruminant reproductive tract, identify the apical epithelial surface as a site of receptor enrichment, and show that the endometrial epithelium retains membrane progesterone receptors while progesterone-responsive gene expression changes dynamically in the conceptus during the peri-implantation period. The validated ruminant-reactive antibodies provide a resource for future functional studies.

Progesterone is essential for the establishment and maintenance of pregnancy, primarily through the classical nuclear progesterone receptor (PGR). However, progesterone also exerts rapid, non-genomic effects through membrane progesterone receptors, including members of the progestin and adipoQ receptor (PAQR) family, whose cellular distribution and potential roles at the human maternal–fetal interface remain poorly understood. We therefore sought to define the cell-type-specific expression landscape of classical and membrane progesterone receptors during early human pregnancy. We analyzed publicly available single-cell RNA-sequencing datasets of the first-trimester human maternal–fetal interface to characterize the expression of PGR and PAQR family members across trophoblast, immune, stromal, and vascular cell populations. Major expression patterns were examined across independent datasets and further assessed using spatial transcriptomic data. PGR expression was predominantly localized to decidual stromal and perivascular populations, whereas individual PAQR family members showed distinct cellular distributions. PAQR6 was enriched in decidual natural killer cells, PAQR7 was broadly expressed in trophoblast populations, PAQR8 was prominently expressed in fetal stromal and macrophage populations, including Hofbauer cells, and PAQR9 showed prominent enrichment in syncytiotrophoblasts. Selected cell-type-specific patterns were further supported by spatial transcriptomic analysis. These findings provide a cell-type-resolved framework for investigating how distinct progesterone receptor systems mediate progesterone signaling across maternal and fetal cellular compartments during early human placentation.

Aim: Natural disasters may disrupt access to assisted reproductive technology (ART) services. This study evaluated the impact of the 2016 Kumamoto earthquake on ART utilization in Kumamoto Prefecture, accounting for nationwide trends and policy changes. Methods: We conducted an interrupted time‐series analysis using annual ART subsidy application data in Kumamoto Prefecture from 2005 to 2020. Nationwide application counts were included as an offset to adjust for national trends related to the 2016 subsidy policy revision. Age‐specific patterns were also examined using normalized indices. Results: In analysis adjusted for nationwide trends, ART subsidy applications showed a significant immediate reduction in 2016 (incidence rate ratio [IRR] = 0.84, 95% confidence interval [CI]: 0.77–0.91), followed by a gradual recovery (IRR for slope change = 1.06, 95% CI: 1.04–1.09). The decline was more pronounced among women aged 40 years and older, whereas applications among younger women remained relatively stable. Conclusions: The 2016 Kumamoto earthquake was associated with a substantial decline in ART subsidy applications in Kumamoto Prefecture beyond nationwide trends. This reduction was most pronounced among women aged 40 years and older, suggesting age‐related differences in responses to disaster‐related disruptions.

Invasive group A streptococcal (iGAS) infection during pregnancy is rare but associated with disproportionately high maternal mortality. Influenza infection has been shown to increase the virulence of Streptococcus pyogenes , and a global resurgence of iGAS has been reported in the post-COVID-19 era. We report a woman in her early 30s at 32 weeks of gestation who developed fulminant iGAS following influenza A infection. Despite antiviral therapy and repeatedly negative rapid antigen tests for group A streptococcus, her condition rapidly deteriorated, resulting in septic shock, acute respiratory distress syndrome and intrauterine fetal death. Intensive multidisciplinary management including emergency delivery, continuous haemodiafiltration and veno-venous extracorporeal membrane oxygenation was required. The patient survived but required right lower limb amputation due to severe ischaemic complications. This case highlights the potential for influenza to precipitate life-threatening iGAS during pregnancy and underscores the need for early recognition when pregnant patients with influenza show unexpected clinical deterioration.

Cervical cancer remains a major global health challenge and a leading cause of gynecological cancer-related mortality, particularly in developing countries. Although persistent human papillomavirus infection is the primary driver of cervical carcinogenesis, host factors such as immune dysregulation and microbiome dysbiosis may contribute to disease progression. Corisin is a microbiota-derived peptide implicated in epithelial injury and fibrosis, but its role in cervical neoplasia is unknown. To investigate its potential involvement, circulating corisin levels were measured in 27 women with cervical intraepithelial neoplasia (CIN) or cervical cancer and compared with those in 15 healthy women. Corisin localization in cervical carcinoma tissues was examined by immunohistochemistry, and its biological effects were evaluated in HeLa cells. Circulating corisin levels were significantly elevated in patients with CIN and cervical cancer, with the highest levels observed in CIN3 and cervical squamous cell carcinoma. Corisin was detected within cervical carcinoma tissues in intracellular and extracellular compartments adjacent to tumor cells. In HeLa cells, corisin accumulated in mitochondria, impaired cell-cycle progression, induced apoptosis, increased p21 expression, and promoted epithelial–mesenchymal transition-like morphological changes. These findings suggest that corisin is elevated from the early stages of cervical neoplasia, is present within the cervical tumor microenvironment, and may contribute to pathogenic cellular processes associated with cervical cancer progression.

Objective: To evaluate maternal characteristics, management practices, and outcomes of placental abruption according to facility type in Japan, and to assess the effectiveness of the country's centralized perinatal care system. Methods: This retrospective observational study used the Diagnosis Procedure Combination database from acute‐care hospitals between May 2014 and April 2024. Cases coded with ICD‐10 O45.0 or O45.9 were included, excluding those with multiple gestations or placenta previa. Patients were categorized into Comprehensive Perinatal Medical Centers (CPMCs) and Regional Perinatal Medical Centers/General Hospitals (non‐CPMCs). The primary outcomes were severe and serious maternal complications as defined by Ananth et al. Secondary outcomes included mode of delivery, hysterectomy, transfusion use and volume, maternal and fetal mortality, intensive care unit admission, estimated blood loss at delivery, and length of hospital stay. Results: Among 771 eligible cases, 257 (33.3%) were admitted to CPMCs and 514 (66.7%) to non‐CPMCs. Referrals (78.2% vs. 68.5%) and ambulance transports (63.0% vs. 37.5%) were significantly more frequent in CPMCs. Severe maternal complications were more common in CPMCs (30.0% vs. 18.3%), particularly coagulopathy and hypovolemic shock, many of which were present at admission. Despite higher baseline severity, rates of serious maternal complications and maternal mortality did not differ. The mean length of hospital stay was shorter in CPMCs (6.0 vs. 6.7 days). Conclusion: Severe placental abruption cases appear to be effectively centralized within this multicenter cohort. The advanced maternal emergency capacity of CPMCs may mitigate morbidity despite higher baseline severity, supporting the functional role of perinatal regionalization within this network.

Management of chronic hypertension in pregnancy remains uncertain, and current guidelines do not address whether the prognostic significance of blood pressure (BP) varies across gestation. To evaluate gestational age–specific associations between maternal BP in the first half of pregnancy and adverse maternal and neonatal outcomes. We conducted a multicenter registry-based cohort study from April 2022 to March 2023 at 65 tertiary referral centers in Japan. A total of 273 women with chronic hypertension and singleton pregnancies were enrolled before 14 weeks’ gestation (median age, 37 years; IQR, 34–40). Systolic and diastolic BP were assessed at three gestational windows (8–9, 10–13, and 14–18 weeks). Aspirin exposure was treated as time-dependent. The primary outcome was a composite of adverse maternal and neonatal events. Cox proportional hazards models and restricted cubic spline analyses were used. Adverse outcomes occurred in 32.6% (89/273). BP–risk associations differed by timing. No association was observed at 8–9 weeks. At 10–13 weeks, risk increased progressively with higher systolic BP, including excess risk in the moderate range (120–134 mmHg) and the highest risk at ≥135 mmHg (HR, 4.11; 95% CI, 1.14–14.82). At 14–18 weeks, a threshold pattern emerged, with increased risk above 140 mmHg (HR, 2.19; 95% CI, 1.40–3.43). Associations were weaker among women who initiated aspirin before 10 weeks, although interaction was not statistically significant. In chronic hypertension, maternal BP during 10–13 weeks of gestation carries heightened prognostic relevance. These findings support gestational age–specific risk assessment and motivate evaluation of early preventive strategies.