Gynecological Endocrinology最新文献

Objective: To analyze the effects of melatonin on angiogenesis in cultured granulosa cells from women undergoing in vitro fertilization, comparing those with female-factor versus male-factor infertility.

Methods: Granulosa cells were obtained from 47 women undergoing in vitro fertilization treatment, including 31 women with female-factor (FFG) and 16 women with male-factor infertility (MFG). Cells from both groups were cultured and divided into four treatment conditions for 96 h: a) control (culture medium without melatonin); b) vehicle (melatonin diluent-ethanol); c) 0.1 µM melatonin; and d) 10 µM melatonin. Expression of 84 genes involved in angiogenesis signaling pathway was analyzed by real-time PCR.

Results: Cultured granulosa cells from both groups expressed aromatase and melatonin receptors. In both groups, cell proliferation peaked at 72 h when exposed to 10 µM melatonin. Of the 84 analyzed genes, three showed significant differential mRNA expression. In the MFG, melatonin at 10 µM upregulated VEGF-B mRNA expression in granulosa cells but downregulated PDGFA and HGF mRNA expression, in contrast to the higher expression of these genes in the FFG under identical conditions.

Conclusion: Melatonin differentially modulates angiogenesis-related gene expression in granulosa cells, indicating that its effects may depend on infertility type and melatonin dose in women undergoing in vitro fertilization.

Objective: To investigate the associations of the neutrophil/albumin ratio (NAR) with type 2 diabetes mellitus (T2DM) in women with a history of gestational diabetes mellitus (GDM).

Methods: We conducted a cross-sectional study involving 782 participants from the National Health and Nutrition Examination Survey. Logistic regression analyses were performed to explore the relationship between NAR and T2DM, adjusting for various confounding factors across different models. Interaction analyses examined the modifying effects of socio-demographic characteristics on the relationship between NAR and T2DM. Mediation analyses were utilized to investigate whether key laboratory indicators and insulin resistance indices mediated the association between NAR and T2DM.

Results: Higher NAR levels were positively associated with T2DM risk. (OR[95%CI]:1.649[1.181,2.309], p = 0.003). Mediation analyses revealed that the effect of NAR on T2DM was entirely mediated through the regulation of red cell distribution width (RDW Coefficient[95%CI]: 0.009[0.001,0.024], p = 0.020) and high-density lipoprotein cholesterol (HDL-C Coefficient[95%CI]: 0.038[0.017,0.067], p < 0.001). Besides, significant interactions and differences were observed in the relationship between NAR and T2DM risk based on body mass index (BMI) (NAR*BMI: interaction coefficient: -0.651, interaction p = 0.027). In individuals with 25 kg/m² ≤ BMI < 30 kg/m², NAR increased the risk of T2DM by regulating the insulin resistance index (HOMA-R) (β[95%CI]: 2.220[0.653,3.787], p = 0.007).

Conclusion: This study revealed that among women with GDM history, NAR may influence the risk of T2DM through the modulation of RDW and HDL-C. Furthermore, NAR and BMI had a significant interaction affecting T2DM risk, particularly prominent in women with 25 kg/m² ≤ BMI < 30 kg/m². Within this subgroup, NAR elevated the risk of T2DM via HOMA-R.

Background: Endometriosis (EMs) is a common gynecological disorder associated with infertility. EMs patients often require assisted reproductive technology (ART) but exhibit lower success rates. This study aimed to characterize the follicular fluid microbiome in EMs patients undergoing in vitro fertilization (IVF) and provide insights into mechanisms underlying lower pregnancy rates.

Methods: Follicular fluid samples were collected from EMs patients and control subjectsundergoing IVF. Microbial DNA was subjected to 16S rRNA gene sequencing. Bioinformatic analyses, including alpha and beta diversity analysis, microbial composition profiling and biomarker identification, were performed.

Results: The follicular fluid microbiome in EMs patients exhibited altered alpha and beta diversity compared to controls. Distinct microbial compositions were observed at various taxonomic levels. Differentially abundant taxa were identified as potential biomarkers for EMs. Microbial profiles were associated with clinical parameters such as oocyte quality and fertilization rates. Models based on microbial profiles were constructed to elucidate the relationship between EMs and IVF outcomes. Functional predictions suggested alterations in metabolic pathways in the follicular fluid microbiome of EMs patients.

Conclusions: This study revealed significant alterations in the follicular fluid microbiome of EMs patients, providing a basis for further research into the role of the microbiome in EMs-related infertility.

Objective: This study aimed to investigate the mechanism of the involvement of USP33 in autophagic ferroptosis in endometriosis (EMs).

Methods: Endometrial stromal cells (ESCs) were isolated from 15 healthy controls and 30 patients with EMs, which were designated NESCs and EESCs, respectively. Real-time PCR and Western blotting were utilized to determine USP33 expression as well as GPX4, LC3II/LC3I, NCOA4, FTH1, LAST1, p-LAST1, YAP, and p-YAP levels. Immunofluorescence was used to detect the colocalization of ferritin and LAMP2, as well as that of LC3 and ferritin. The levels of ROS, Fe²⁺, MDA, and GSH were measured to assess ferroptosis. An LDH assay was performed to evaluate cell death. A co-IP assay was implemented to identify the interaction between USP33 and LAST1 and detect the level of LAST1 ubiquitination. The stability of the protein was also detected via a cycloheximide (CHX) assay.

Results: USP33 was underexpressed in EMs patients. Loss of USP33 conferred resistance to ferroptosis in EESCs, as evidenced by increased proliferation; decreased levels of ROS, Fe²⁺, and MDA; elevated levels of GPX4 and GSH; and reduced cell death. In addition, USP33, which is localized in autophagosomes, was suggested to promote the degradation of ferritin in autophagosomes. Furthermore, USP33 repressed the Hippo-YAP pathway by suppressing LATS1 ubiquitination, thereby contributing to the reduced resistance of EESCs to ferroptosis.

Conclusion: USP33 impedes the ubiquitination of LAST1 and represses the Hippo/YAP pathway, thus facilitating ferritinophagy and ferroptosis in EMs.

Objective: The purpose of this systematic review and meta-analysis is to assess the association of handgrip strength (HGS) in subjects with high-normal or mildly elevated and low-normal serum uric acid (SUA) reported by quartiles.

Methods: The research protocol was registered at PROSPERO (CRD420251050351). We searched four databases to obtain relevant articles reporting HGS by SUA quartiles in subjects without gout. Outcomes were compared by combining the third and fourth SUA (higher) quartiles versus the first and second (low) quartiles. The risk of bias was assessed using the Newcastle‒Ottawa Scale, and heterogeneity with the I² test. The results are reported as the mean difference (MD), standardized MD (SMD), or odds ratio (OR).

Results: Seven cross-sectional studies, including 18,765 adult subjects with higher SUA quartiles showed significant higher HGS (SMD: 0.21, 95% confidence interval [CI]: 0.03, 0.39), body mass index (MD: 1.02 kg/m², 95% CI: 0.48, 1.55), total cholesterol (SMD: 0.14, 95% CI: 0.05, 0.24), LDL-cholesterol SMD: 0.13, 95% CI: 0.09, 0.17), and triglycerides (SMD: 0.26, 95% CI: 0.11, 0.41) than those with lower SUA quartiles. HDL-cholesterol was significantly reduced in subjects with higher SUA (SMD: -0.13, 95% CI: -0.20, -0.07). High SUA levels were associated with a drinking history (OR: 1.21, 95% CI: 1.10, 1.34) and hypertension (OR: 1.51, 95% CI: 1.15, 1.99).

Conclusions: Subjects with higher normal SUA levels showed higher HGS compared to those with lower normal levels.

Background: Astrocytes, once regarded as passive support cells, are recognized as active regulators of synaptic organization and neuronal integration. Through extension or retraction of their processes, astrocytes influence synapse formation and elimination. Astrocytes express estrogen receptors, and animal studies have shown that estradiol modifies astrocytic morphology in relation to synaptic density.

Objective: To examine the effects of estradiol and two clinically available selective estrogen receptor modulators (SERMs), tamoxifen, and raloxifene on astrocyte processes in human brain tissue.

Methods: Human temporal lobe cortical slices were incubated for 60 min with estradiol (10 nM), tamoxifen (1.0 µM), or raloxifene (1.0 µM), and the results were compared with untreated control slices. Astrocytes were visualized by immunostaining for the glial cytoskeletal marker glial fibrillary acidic protein (GFAP). Light microscopy image analysis was used to quantify astrocytic process thickness and branching, using Neurolucida® software.

Results: Control slices exhibited astrocytic branch extension and thinning during the incubation period. Similar morphological changes were observed in the tamoxifen-treated slices. In contrast, raloxifene treatment was associated with a significant reduction in astrocyte branching and thinning compared with controls (p = 0.01 for primary processes). Estradiol treatment resulted in intermediate reductions in astroglial process measures that did not reach statistical significance.

Conclusions: Estradiol, tamoxifen, and raloxifene - widely used hormonal agents - were associated with distinct effects on astrocyte morphology in human cortical tissue. These findings support a role for estrogen receptor modulation in astroglial structural regulation and suggest a potential cellular mechanism contributing to central nervous system symptoms reported in clinical settings.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS are at an increased risk for adverse pregnancy outcomes, such as miscarriage and preterm birth. Endometrial receptivity plays a pivotal role in embryo implantation. However, there has been limited review or discussion regarding potential alterations in endometrial receptivity in PCOS patients, the nature of these changes, and their underlying mechanisms. In this review, we aim to summarize the alterations in endometrial receptivity associated with PCOS, highlight the impact of PCOS on endometrial receptivity, and explore the underlying mechanisms. Abnormal expression of key receptivity markers has been observed in both PCOS patients and animal models, which may contribute to reduced endometrial receptivity. The factors leading to impaired endometrial receptivity in PCOS are multifaceted, including hormonal imbalances, metabolic disturbances, chronic inflammation, and microbiota alterations. However, the intricate mechanisms behind PCOS-related endometrial dysfunction remain poorly understood. Further research is essential to unveil these complex mechanisms and improve fertility outcomes for women with PCOS.

Objective: To evaluate the effect of intrauterine infusion of platelet-rich plasma (PRP) on luteal support and pregnancy outcomes in patients with thin endometrium undergoing frozen-thawed embryo transfer (FET).

Methods: A total of 160 patients with thin endometrium undergoing FET from March 2023 to March 2024 were assigned to the observation group (PRP infusion, n = 80) or the control group (conventional treatment, n = 80). All patients underwent hormone replacement therapy cycles,with PRP infused on days 9, 11, and 13 in the observation group. Outcomes included endometrial thickness, uterine hemodynamic parameters (PI, RI), PBAC-assessed menstrual volume, pregnancy outcomes, and embryology-related variables. Logistic regression identified independent factors associated with clinical pregnancy. Adverse events were also recorded.

Results: Post-treatment, the observation group had greater endometrial thickness and lower PI and RI values than the control group. PBAC scores, clinical pregnancy rate (36.25% vs. 21.25%), and live birth rate (25.00% vs. 12.50%) were significantly higher, while preterm birth rate did not differ. Embryo transfer-related variables were comparable between groups. Multivariate analysis identified PRP infusion and endometrial thickness at transfer as independent protective factors for clinical pregnancy, whereas advanced age was an unfavorable factor. No obvious adverse events occurred.

Conclusion: PRP infusion enhances endometrial receptivity by improving thickness and blood perfusion, thereby increasing pregnancy and live birth rates in thin endometrium patients undergoing FET. It is safe and may be used as an effective adjunct in endometrial preparation.

Objective: To compare dydrogesterone versus levonorgestrel-releasing intrauterine system (LNG-IUS) for abnormal uterine bleeding (AUB) management with long-term follow-up and etiology-stratified analysis.

Methods: This single-center retrospective cohort study analyzed reproductive-aged women with International Federation of Gynecology and Obstetrics (FIGO)-classified AUB receiving dydrogesterone (n = 131) or LNG-IUS (n = 118). Propensity score matching balanced baseline covariates between groups (n = 104 pairs). Primary outcomes were bleeding control rates (composite: hemoglobin increase ≥ 1.5 g/dL, ≥ 50% Pictorial Blood Loss Assessment Chart [PBAC] reduction, no rescue interventions) at 3 and 12 months. Secondary outcomes included 24-month recurrence and adverse events (AEs).

Results: LNG-IUS demonstrated superior 3-month bleeding control versus dydrogesterone (82.7% vs. 65.4%; relative risk [RR] 1.26, 95% confidence interval [CI] 1.08-1.48; p = 0.002). At 12 months, bleeding control rates were comparable between groups (78.8% vs. 72.1%; RR 1.09, 95% CI 0.96-1.24; p = 0.17). LNG-IUS significantly reduced 24-month recurrence risk (hazard ratio [HR] 0.48, 95% CI 0.32-0.72; p < 0.001), particularly for structural AUB (HR 0.39, 95% CI 0.24-0.64). Subgroup analysis revealed LNG-IUS superiority in adenomyosis at 12 months (88.2% vs. 60.0%; RR 1.47, 95% CI 1.24-1.74; p < 0.001) but comparable efficacy in nonstructural AUB (76.6% vs. 72.9%; RR 0.95, 95% CI 0.78-1.16; p = 0.63). Dydrogesterone exhibited higher systemic AEs (28.2% vs. 13.6%; p = 0.003), while LNG-IUS had device-related events including expulsion (5.1%).

Conclusion: LNG-IUS offers superior short-term bleeding control and sustained long-term recurrence prevention, especially for structural AUB. Dydrogesterone effectively manages nonstructural etiologies but carries higher systemic adverse event rates. Treatment selection should be etiology-guided, balancing immediate symptom control versus recurrence prevention and individualized safety considerations.