Reproductive Sciences最新文献

Female genital tuberculosis (FGTB), a form of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis (MTB), is an under-recognized but significant cause of female infertility, particularly in developing countries. It primarily spreads through the hematogenous route and often presents with non-specific or asymptomatic clinical features, complicating early diagnosis. Latent tuberculosis (LTB) is increasingly being identified among women with unexplained infertility and may impair reproductive outcomes by affecting ovarian reserve, endometrial receptivity, and implantation. Traditional diagnostic methods-such as smear microscopy, culture, imaging, and histopathology-suffer from low sensitivity and long turnaround times. Newer molecular techniques, including GeneXpert MTB/RIF and nucleic acid amplification test (NAAT), offer faster and more accurate detection. A comprehensive, multimodal diagnostic approach is essential for timely intervention. This review highlights the epidemiological trends, diagnostic advancements, clinical manifestations, and fertility implications of FGTB. Improved awareness and accurate detection strategies are critical for enhancing fertility outcomes in affected women.

Endometrial carcinoma, the second most common gynecological cancer, is increasingly affecting younger women, particularly due to rising obesity rates. The need for precise molecular tools is paramount for better categorization and risk stratification, especially in fertility preservation, as current methods often fall short. Fertility preservation is considered for early-stage, nonmetastatic cases, but the role of molecular classifications in this area remains underexplored. We present the case of a 35-year-old woman with grade 2 p53abn endometrioid endometrial cancer who sought fertility preservation. Her initial treatment involved hysteroscopy-guided resection, hormonal therapy with megestrol acetate (MA), and close monitoring, but the disease recurred within six months. A literature review reveals that fertility preservation in p53abn endometrial carcinoma is poorly documented, with variable outcomes. Many cases indicate a poor response to progestin therapy and a heightened risk of recurrence, highlighting the need for personalized treatment approaches. Additionally, our case identifies "a novel PTEN somatic mutation (Tier 2C)" that has not been previously reported in endometrial cancer. This case underscores the essential role of molecular profiling in clinical decision-making and the need for ongoing research into molecular pathways. Integrating molecular classifiers into routine practice is crucial for improving risk stratification and treatment outcomes, especially in young women pursuing fertility preservation.

Endometriosis is a gynecological inflammatory disorder characterized by the presence of endometrial tissue outside of the uterus. It affects 10-15% of reproductive aged women, causing pelvic pain and infertility. Existing treatments for endometriosis, including invasive and non-invasive therapies, are plagued by treatment resistance and adverse effects. Dissecting molecular mechanisms or signaling pathways that are involved in the pathophysiology of endometriosis may reveal new molecular targets. IL-6 is classically considered an inflammatory cytokine that is highly expressed in endometriosis. Here, we studied the effect of an anti-IL-6R antibody that interferes with the IL-6 signaling pathway in endometriosis. Endometriosis was induced in c57BL/6 female mice that were subsequently treated with either a murine-specific anti-IL-6 receptor monoclonal antibody (15A7) or IgG2b as a control. We found that there was no change in endometriosis lesion number or volume. However, we observed that the lesion attachment to underlying peritoneum was significantly increased after treatment with the 15A7 antibody, indicating a possible effect on invasion. As expected, IL-6 mediated pathways of p38 MAPK and STAT3 in JAK/STAT signaling were decreased in the anti-IL-6R treatment group compared to isotype control group. There were no differences in N-Cadherin and ICAM between groups. IL-6 had a paradoxical role in endometriosis - preventing or limiting invasion and adhesion.

In recent years, with the increasing use of ZnONPs as a feed additive in animal diets, their potential impact on the animal reproductive system has garnered growing attention. The present study aimed to investigate the ameliorative effects of SI on ZnONPs-induced toxicities in mice. The experiment was divided into five groups (n = 8): normal saline (control), ZnONPs (50 mg/kg), ZnONPs (100 mg/kg), ZnONPs (50 mg/kg) + SI (50 mg/kg) + , ZnONPs (100 mg/kg) + SI (50 mg/kg). The experiment lasted for 45 days. Mice treated with ZnONPs exhibited a significant reduction in body weight (p < 0.05 or p < 0.01) and testicular index (p < 0.01). Severe histopathological damage was observed in the affected testes, accompanied by a marked increase in Zinc (Zn) content in both blood and testicular tissues (p < 0.01), elevated levels of apoptosis (p < 0.01), and decreased activities of antioxidant enzymes, including superoxide dismutase (SOD) (p < 0.01). RNA-seq analysis revealed that exposure to different concentrations of ZnONPs resulted in the enrichment of differentially expressed genes (DEGs) in mouse testicular tissues, primarily in pathways related to signal transduction, cell differentiation, and apoptosis. Additionally, ZnONPs were found to effectively modulate the expression levels of oxidative stress- and apoptosis-related genes via the JAK-STAT signaling pathways and MAPK signaling pathway. Furthermore, exposure to ZnONPs caused varying degrees of changes in the expressions of Stat1 (p < 0.01), Junb (p < 0.01), Ddx4 (p < 0.01)and Ar (p < 0.05 or p < 0.01) in the testicles of mice. In contrast, after SI treatment, the above abnormal changes induced by ZnONPs were significantly decreased. Finally, it could be concluded that SI could decrease the reproductive toxicities caused by ZnONPs in mice.

Endometriosis is a chronic gynecological disease characterized by the presence of endometrial-like tissue outside the uterus, leading to pain and infertility. Recent research has highlighted the important role of the microbiome in various health conditions, including endometriosis. The aim of this review is to examine the central role of the microbiome in the development and treatment of endometriosis. Key findings include the influence of the gut microbiota on estrogen metabolism, whereby certain bacteria can increase estrogen levels and systemic inflammation and exacerbate endometriosis. Changes in the vaginal and endometrial microbiota are also associated with the disease, as they influence inflammatory and estrogen-dependent metabolic pathways. Dysbiosis in various microbiomes can affect inflammatory pathways, with a shift in the vaginal microbiota to the upper reproductive tract affecting endometriosis without symptoms. Probiotic interventions show promise in restoring a healthy microbiota and improving outcomes, with clinical trials demonstrating the efficacy of lactobacilli-based medications for pain relief. In addition, diet and lifestyle changes can directly impact the gastrointestinal microbiome, reducing inflammation and potentially influencing endometriosis. Future research should focus on establishing comprehensive microbiome profiles, mechanistic studies and longitudinal studies to discover new therapeutic targets and improve clinical outcomes for women with endometriosis.

Uterine leiomyomas are the most common benign smooth muscle tumors in women of reproductive age. Recent technological advances have enhanced the potential of proteomic studies to identify proteins and related signaling pathways involved in leiomyoma pathogenesis. This study performed comprehensive proteomic analyses of three leiomyoma subtypes, classified by their localizations, to provide new insights and a valuable resource for further studies. Tissue samples from both leiomyoma and normal myometrial tissues were collected from individuals undergoing hysterectomy for symptomatic leiomyomas. Proteins were extracted from tissue samples, enzymatically digested to generate peptides, and subsequently analyzed using high-resolution mass spectrometry (HR-MS). Biological significance and related pathways of differentially expressed proteins were revealed by Gene Ontology (GO) analyses. MS analyses revealed significant expression changes in 143, 152 and 146 proteins in submucosal, subserosal and intramural myomas, respectively. Top enriched categories of dysregulated proteins included RNA binding, oxidoreductase activity, cytoskeletal structural components, glutathione transferase activity, extracellular matrix organization, innate immunity, post-translational phosphorylation. The classification of differentially expressed proteins (DEPs) also highlighted the metabolite interconversion enzyme family in all three groups. Hydrolase, oxidoreductase and transferase subfamilies were common to all three groups, while isomerase, ligase and lyase subfamilies were present in the subserosal and intramural groups. Proteomic analyses provided important information about the dysregulated proteins in uterine leiomyomas and revealed various pathways to which they are related. The findings emphasize the need for further research, especially on the effects of oxidative stress on the immune response against tumor cells, the role of extracellular matrix proteins and enzymes in metabolic pathways.

Ferroptosis and insulin resistance (IR) play crucial roles in the development of gestational diabetes mellitus (GDM). This study aims to analyze the effects of perillaldehyde (PAE) on ferroptosis and IR in human trophoblast cells, as well as its underlying mechanism in these effects. In this study, human trophoblasts (HTR-8/SVneo cells) treated with high glucose or in combination with insulin were used as in vitro models of GDM. The protective effects of PAE were evaluated by detecting insulin resistance and ferroptosis. GSE datasets (GSE154414 and GSE54157), SwissTargetPrediction, and GeneCards were used for gene target prediction. Results showed that PAE mitigated the decrease in HTR-8/SVneo cell viability caused by HG treatment. PAE exerted a protective effect against HG-triggered ferroptosis in HTR-8/SVneo cells by reducing ROS, Fe²⁺, and MDA levels, while increasing GSH and GPX4 levels and SOD activity. PAE alleviated IR in HTR-8/SVneo cells by increasing IRS1 and GLUT4 mRNA levels and glucose uptake, while decreasing IGF-1 mRNA level. PAE inhibited the expression of PTPN1 in HTR-8/SVneo cells with HG treatment. PTPN1 overexpression reversed the effect of PAE on ferroptosis in HTR-8/SVneo cells with HG treatment. PTPN1 overexpression counteracted the effects of PAE on IR in HTR-8/SVneo cells. PAE activated the Akt/Foxo signaling pathway by downregulating PTPN1 in HTR-8/SVneo cells under HG conditions. Akt/Foxo1 activation counteracted the effects of PTPN1 overexpression on ferroptosis and IR in HTR-8/SVneo cells with HG treatment. In conclusion, PAE attenuated IR and high glucose-triggered ferroptosis in trophoblast cells via regulation of the PTPN1/Akt/Foxo1 signaling pathway.

The effect of polycystic ovary syndrome (PCOS) on the fatty acid (FA) content of follicular fluid (FF) is not fully understood. The present study aimed to determine whether the FA composition of FF phospholipids (PLs) and triglycerides (TGs) undergoes alterations in women with PCOS. A total of 40 subjects, including 20 PCOS patients and 20 controls, were enrolled. Thin-layer chromatography followed by gas chromatography was carried out to isolate FF lipid fractions and measure relative concentrations of their FAs, respectively. Percentages of individual FAs in FF PLs and TGs did not statistically differ between the control and PCOS groups (p > 0.05), other than palmitoleic acid, which significantly decreased and increased in PLs and TGs of women with PCOS, respectively (p < 0.05). There were positive correlations between intrafollicular levels of androgens and PL levels of several n-6 polyunsaturated FAs in the PCOS group (r > 0.4, p < 0.05). In addition, relative concentrations of eicosapentaenoic acid in both PL and TG fractions were inversely correlated with the fertilization rate (r < -0.4, p < 0.05). PCOS women with positive pregnancy outcomes also had higher PL and TG stearic acid with concomitant lower docosahexaenoic acid and peroxidizability index in PL and TG fractions, respectively (p < 0.05). It could be concluded that PCOS was associated with minor alterations in the FA composition of FF PLs and TGs. Furthermore, there were differential fraction-dependent associations between FF FA profile and biochemical and reproductive parameters in women with PCOS.

Gut microbiota plays a critical role in maintaining reproductive homeostasis, and mounting evidence highlights probiotic supplementation as a promising therapeutic candidate owing to its immunomodulatory potentials. Neurotensin (NTS), a tridecapeptide neuropeptide, has been shown to link with the regulation of inflammation and reproductive processes. This study aims to evaluate the possible simultaneous ameliorative effect of NTS receptor 1 agonist PD149163 co-administration with multi-strain probiotics in lipopolysaccharide/LPS induced ovarian dysfunction. Female Swiss albino mice (8 weeks old) were randomly assigned to seven groups: control, LPS (1 mg/kg bw), LPS + PD149163 (50 µg/kg bw), LPS + probiotics (0.6 gm/kg bw/day), LPS + PD149163 + probiotics, PD149163, and probiotics. After 32 days, plasma and ovarian samples were collected for biochemical and histological analyses. Additionally, an in-silico approach was employed to assess the potential interaction of probiotic-derived metabolites (butyrate and propionic acid) with the key proteins of TLR4/MyD88/NF-κB signalling pathway (TLR4/MD-2 complex, MyD88 and NF-κB). Co-administration of PD149163 with multi-strain probiotics attenuated inflammatory markers (NF-κB, TNF-α, IL-6), restored anti-oxidant enzyme activity (SOD, CAT), reduced lipid peroxidation (LPx), normalized hormonal levels (NTS, LH, FSH, E2) and improved ovarian histopathological features. Co-supplementation of probiotics with PD149163 as an adjunct therapy has shown superior efficacy in mitigating the ovarian dysfunction compared to employing single treatment approach. This ameliorative effect is presumably mediated by suppressing TLR4/MyD88/NF-κB signalling pathway, thereby dampening inflammatory cascade and alleviating ovarian dysfunction. Therefore, further investigations are warranted to unravel the underlying mechanisms of probiotic action on reproductive physiology, thereby providing therapeutic insights for the management of sepsis-related reproductive dysfunction.

Preeclampsia (PE), a severe pregnancy complication, arises from placental hypoxia-induced mitochondrial and endoplasmic reticulum (ER) oxidative stress, contributing to inadequate spiral artery remodeling and endothelial dysfunction. Calpastatin, a mitochondrial protective protein, mitigates oxidative stress-related pathologies, but its role in PE remains unclear. This study investigated the effects of Calpastatin on trophoblast cellular proliferation, migration, invasion, apoptosis, and the expression of autophagy protein (PINK1), mitochondrial dynamics protein (Mfn2), ER stress protein (GRP78), ATP, Ca²⁺, and mitochondrial membrane potential under hypoxia using transfected HTR8-SVneo cells. Calpastatin overexpression significantly enhanced proliferation, migration, and invasion while reducing apoptosis (P < 0.05); knockdown inversely affected these parameters under normoxic conditions. Under hypoxia, overexpression further amplified proliferation and migration (P < 0.01), whereas knockdown reduced migration at 48 h (P = 0.04) but not proliferation. Invasion decreased and apoptosis increased in both groups (P < 0.05). Calpastatin overexpression upregulated PINK1, downregulated Mfn2/GRP78, increased ATP and mitochondrial membrane potential, and reduced Ca²⁺. Conversely, knockdown suppressed Pink1/Parkin, elevated Mfn2/Drp1/GRP78, decreased ATP, and increased Ca²⁺ and mitochondrial depolarization (P < 0.05). These findings demonstrate calpastatin promotes trophoblast function by maintaining mitochondrial-ER contact sites stability and ATP production, Ca²⁺ homeostasis, and mitophagy mechanism, suggesting its critical role in PE pathogenesis.