Background Diethylstilbestrol (DES) is a potent synthetic estrogen implicated in endometrial carcinogenesis through estrogen receptor (ER)-dependent mechanisms. However, the temporal relationship between DES exposure, estrogen receptor alpha (ERα) expression, and histopathological progression of endometrial lesions remains incompletely defined in vivo. Methods An experimental in vivo study was conducted using 32 eight-week-old female mice randomly assigned to eight groups, including two untreated controls and six DES-treated groups with varying exposure and observation durations. DES was administered at 1000 µg according to predefined schedules. Uterine tissues were examined histopathologically using HE staining, and ERα expression was evaluated by immunohistochemistry using the modified Remmele Immunoreactive Score. Statistical analyses included one-way ANOVA with Tukey post hoc testing, Kruskal–Wallis and Mann–Whitney U tests, and path analysis to assess mechanistic relationships. Results ERα expression differed significantly among groups, with the highest expression observed in mice receiving prolonged DES exposure followed by extended observation. Histopathological evaluation demonstrated a clear progression from normal endometrium in control groups to higher-grade lesions in DES-treated groups, with severe (Grade 3) changes predominating in high exposure cohorts. Path analysis revealed a significant association between DES exposure and ERα expression, as well as a positive effect of ERα on EC development. Conclusions DES promotes endometrial carcinogenesis through ERα dependent mechanisms in vivo. Increased ERα expression parallels histopathological progression, and mechanistic analysis confirms ERα as a key mediator linking synthetic estrogen exposure to tumor development. These findings underscore the central role of estrogen signaling in DES-induced EC.
Background: Bacterial vaginosis (BV) is the most prevalent vaginal infection among reproductive-age women and is associated with increased susceptibility to gynecological complications. Current antibiotic treatments achieve high initial cure rates but show high rates of recurrence, partly due to their inability to remove persistent biofilms. p Hyph is a novel, non-antibiotic treatment that lowers vaginal pH, promoting Lactobacillus growth and biofilm disruption. Objective: To evaluate the immediate and long-term effects of p Hyph on the vaginal microbiome, BV resolution, and symptom reduction. Study design: In a randomized, controlled, partially blinded study, 61 women with clinically diagnosed BV were randomized to immediate (IT, n = 35) or delayed (DT, n = 26) treatment. Vaginal swabs were collected before treatment, after 6 days, and during maintenance to Day 70. Microbiome composition was analyzed using a qPCR panel targeting 47 bacterial and 6 fungal species. Results: Compared to controls , p Hyph reduced the abundance of multiple BV-associated species and increased Lactobacillus iners following 6-day treatment (median 8.96 ×10 3 [Q1–Q3: 3.10 ×10 3 –2.72 ×10 4 ] vs. median 9.44 × 10² [Q1–Q3: 0.00–4.29 × 10 ³] normalized qPCR counts, p < 0.05). Additionally, p Hyph reduced BV-related symptoms, particularly fishy odor (p < 0.05). Treatment promoted a shift to CST III microbiome composition, and maintenance dosing was associated with sustained Lactobacillus abundance up to Day 70. Conclusions: p Hyph shows potential as an alternative BV treatment by reducing BV-associated pathogens while promoting lactobacilli. Extended dosing may enhance microbiome stability.
Background Findings regarding the reproductive toxicity effect of heavy metals on sperm parameters and sex hormones level remain inconsistent. This study systematically reviewed and pooled the existing literature to assess the associations of heavy metal levels with sperm parameters and sex hormones. Methods In this systematic review, international databases including PubMed, Scopus, and Web of Science were searched until 31 March 2025 according to PRISMA guidelines. Observational studies assessing heavy metal concentrations in biological samples and their associations with sperm parameters or sex hormone levels were included. The chi-square-based Q test and I-squared statistics were used to assess the heterogeneity, and pooled estimates were obtained using a random-effects meta-analysis model. Results Eighteen studies involving 4041 participants were included. Qualitative synthesis revealed heterogeneous findings across heavy metals and sperm parameters, with significant findings reported mainly for Cd and Pb, while most associations with reproductive hormones were non-significant. Meta-analysis demonstrated a significant inverse association between seminal Cd and sperm motility (pooled Fisher’s z = -0.17, 95% CI: −0.30 to −0.04; I² = 0%), whereas no significant pooled associations were observed for seminal Pb. Conclusions The current evidence does not demonstrate consistent associations between heavy metal exposure and male reproductive parameters; however, limited significant inverse correlations were identified between seminal Cd and sperm motility. Evidence regarding reproductive hormones was limited and largely inconclusive, highlighting the need for larger, well-designed prospective studies.
Background Gestational diabetes mellitus (GDM) screening practices remain debated. One-step strategies identify more women with GDM, but their population-level benefits remain uncertain. Belgium provides a natural experiment: Wallonia recommended screening with the one-step strategy based on IADPSG criteria in 2012, whereas Flanders continued to recommend a two-step approach. Objective To compare changes in birthweight-related outcomes and recorded hyperglycaemia in pregnancy (HiP) between these regions after their screening recommendations diverged. Methods We conducted a population-based study including all singleton live births in Wallonia and Flanders during 2010–2011, before the adoption of one-step screening recommendations in Wallonia (n = 211,774), and during 2015–2018 (n = 399,376)., after a transitional implementation period ( between 2012 and 2014). HiP was defined as recorded gestational or pre-existing diabetes. Crude prevalences were calculated by region and period. Logistic and multinomial logistic models estimated changes in HiP, small-for-gestational-age (SGA), large-for-gestational-age (LGA), and macrosomia. Adjusted ratios of odds ratios (aRORs) compared post-versus-pre changes in Wallonia with those in Flanders, accounting for maternal sociodemographic characteristics, body mass index, and parity. Results HiP prevalence increased from 2.74% to 4.29% in Flanders and from 5.95% to 8.52% in Wallonia. However, the relative increase was smaller in Wallonia than in Flanders (aROR 0.92, 95% CI 0.87–0.97). The prevalence of SGA decreased from 6.54% to 5.72% in Flanders and from 8.60% to 8.09% in Wallonia, with a smaller relative decrease in Wallonia (aROR 1.11, 95% CI 1.05–1.15). No differential change between regions was observed for LGA (aROR 1.00, 95% CI 0.97–1.04). Macrosomia remained broadly stable in both regions (9.29–9.16% in Flanders and 6.19–6.51% in Wallonia), although a trivial differential change was observed (aROR 1.05, 95% CI 1.00–1.09) Conclusions Although the absolute increase in HiP prevalence was greater in Wallonia, the relative increase in the odds of HiP was smaller than in Flanders, where two-step screening recommendations were maintained. No consistent improvement in birthweight-related outcomes was observed. These findings suggest that changes in screening recommendations may not translate into clinically meaningful population-level changes, although we cannot exclude challenges in their implementation and uptake in clinical practice.
Background Endometriosis-associated ovarian cancer is uncommon and is most often represented by endometrioid and clear cell carcinomas. Synchronous contralateral borderline ovarian tumours are uncommon and may be missed when gross intraoperative assessment is reassuring. Case A 43-year-old woman with a confirmed diagnosis of endometriosis for approximately 5 years presented with worsening pelvic pain and menstrual symptoms. A left ovarian endometrioma increased from 6.1 × 6.8 × 5.2 cm in April 2024 to 8.8 × 9 × 9.5 cm in April 2025, with subsequent MRI showing a complex mass with solid components (O-RADS MRI 5). CA-125 was 408.6 U/mL and CA 19–9 was 643.58 U/mL; RMI-I was 1225.8 (U = 3, M = 1, CA-125 = 408.6). Staging laparotomy was performed. Histopathology demonstrated grade 2 endometrioid adenocarcinoma arising in an endometriotic cyst of the left ovary, FIGO stage IC1, while the grossly normal-appearing right ovary contained a borderline seromucinous tumour with endometrioid differentiation. The omentum, peritoneal cytology, and all 31 sampled lymph nodes were negative for malignancy. Immunohistochemistry supported endometrioid carcinoma. Conclusion This case highlights the importance of interval change and suspicious imaging features in an endometrioma, the limitations of gross intraoperative assessment of the contralateral ovary, and the value of complete histopathological examination in identifying synchronous bilateral ovarian pathology.
