Reproductive Sciences最新文献

The GATA gene family encodes highly conserved zinc-finger transcription factors that facilitate the development and function of multiple organ systems including the uterus. In the endometrium, GATA2 functions in a positive autoregulatory loop with the progesterone receptor (PGR) and colocalizes with PGR on chromatin to promote PGR transcriptional programs. GATA2 also has PGR-independent functions that maintain endometrial cell identity, and GATA2 transcripts reportedly are down-regulated in endometrial disorders including endometriosis. This event is accompanied by a reciprocal increase in GATA6. Here, we applied custom anti-GATA2 monoclonal antibodies and performed GATA2 immunohistochemistry (IHC) on patient endometrial tissues corresponding to proliferative, secretory, inactive, and hormone-treated endometrium, as well as endometriosis and endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (EAH/EIN). We also performed IHC for the estrogen receptor, PGR, and GATA6 in relevant groups. The results reveal a tight correlation between GATA2 and PGR expression in the glandular and stromal cells of benign endometrium. GATA2 expression is markedly reduced in stromal but not glandular cells in endometriosis and EAH/EIN. This reduction in GATA2 expression does not lead to a detectable increase in GATA6 expression in endometriosis. Although average glandular GATA2 expression was preserved in endometriosis and EAH/EIN cases, its expression was decoupled from PGR, implying that alternative pathways regulate GATA2 levels in these disorders. Our findings indicate that GATA2 dysregulation is a feature of endometriosis and EAH/EIN, and support a model whereby loss of stromal GATA2 in these disorders contributes to their progesterone insensitivity.

In 2010, the estimated annual cost of uterine fibroids in the United States ranged from 5.9 to 34.4 billion USD. In the past decade, more uterine-sparing and fertility preserving interventions have become available to treat symptomatic fibroids. This comparative cost-analysis aims to evaluate change in societal costs of uterine fibroids in the US between 2010 and 2022 given changing fibroid and obstetric management, population growth, and inflation. A systematic review was conducted to update uterine fibroid, treatment, and obstetric complication prevalence, direct costs of medical and surgical interventions, indirect productivity costs, and obstetric costs attributable to fibroids in 2022. A comparative cost-analysis with paired t-tests was performed using baseline data published in 2010. Percent (%) changes between 2010 and 2022 were reported. NIH research funding for fibroids and other common diseases was compared. All costs were converted to 2023 USD. The number of US women with uterine fibroids increased by 10.6% from 2010 to 2022. Over this period, the economic burden of uterine fibroids increased up to 41.4 billion USD compared to 34.4 billion USD in 2010. Overall costs increased to 42.2 billion USD after incorporating new costs associated with MRgFUS and infertility. Direct costs of medical management decreased while costs of surgical interventions increased as a result of evolving treatment-seeking behavior. Lost work costs continue to account for the largest proportion of the economic burden for fibroids. Cesarean section delivery remains the largest contributor (average 80.0%) to indirect obstetrical costs. Despite the rise in the number of individuals affected by uterine fibroids and its sizable annual cost to society, uterine fibroids research continues to be underfunded.

In the present study, we examined the functional interrelationships between microRNAs and plant polyphenols in the regulation of ovarian cell functions. For this purpose, we compared the basic functions of porcine ovarian granulosa cells with or without transfection with miR-152 mimics that were cultured with or without quercetin. The expression levels of miR-152, cell viability, cell proliferation (accumulation of proliferating cell nuclear antigen, PCNA), apoptosis (accumulation of Bax) and the release of progesterone, estradiol, and insulin-like growth factor I (IGF-I) were analyzed by real-time quantitative polymerase chain reaction (RT‒qPCR), the Trypan blue exclusion test, quantitative immunocytochemistry, and enzyme-linked immunosorbent assays (ELISAs). Transfection of cells with miR-152 mimics increased miR-152 expression, reduced cell viability, proliferation, apoptosis, and estradiol output, and promoted the release of progesterone and IGF-I. Quercetin decreased all measured parameters. Moreover, quercetin promoted the effect of miR-152 on cell viability, apoptosis, and estradiol and mitigated the effect of miR-152 on cell proliferation and IGF-I output. For instance, miR-152 mimics promoted the effect of quercetin on cell viability, apoptosis, and estradiol but prevented the effect of quercetin on PCNA. These observations demonstrated the involvement of miR-152 and quercetin in the control of ovarian cell functions and their functional interrelationships, mainly synergism, in the regulation of these functions.

Preeclampsia (PE) is a specific hypertension-related disease in pregnancies, causing adverse pregnancy outcomes. Endothelial cell dysfunction is a major etiology of PE, of which the regulation could affect disease progression. This study focused on hsa_circ_0088196, evaluating its clinical significance in PE and its effect on endothelial cell injury, aiming to identify a novel biomarker for PE and complete its regulating mechanism in disease development. The study enrolled 165 normal pregnancies and 165 pregnancies with gestational hypertension. The significance of hsa_circ_0088196 in discriminating gestational hypertension, predicting PE, and predicting adverse pregnancy outcomes was evaluated based on its serum expression. The effect and mechanism of hsa_circ_0088196 in HUVEC injury were assessed by CCK8, Transwell, ELISA, and western blotting. Significant downregulation of hsa_circ_0088196 could distinguish gestational hypertension pregnancies and predict the risk of PE. Gestational hypertension pregnancies developed PE showed a lower serum hsa_circ_0088196 level, which also discriminated PE patients, predicted severe conditions and adverse pregnancy outcomes. Overexpressing hsa_circ_0088196 alleviated the enhanced proliferation, migration, inflammation, and angiogenesis by hypoxia/reoxygenation (H/R), which was reversed by miR-145-5p. Silencing miR-145-5p showed similar effects on H/R-induced endothelial cell injury, which was reversed by FLT1. Moreover, FLT1 was positively regulated by hsa_circ_0088196, indicating its involvement in the regulation of HUVEC injury by hsa_circ_0088196. Reduced serum hsa_circ_0088196 served as a biomarker for the diagnosis of gestational hypertension, risk evaluation of PE, and the prediction of adverse pregnancy outcomes. hsa_circ_0088196 suppressed endothelial cell injury induced by H/R through modulating the miR-145-5p/FLT1 axis.

This study aims to assess the effectiveness of pulsed gonadotropin-releasing hormone (GnRH) micropump replacement therapy in the treatment of hypogonadotropic hypogonadism (HH) caused by primary empty sella (PES).The efficacy of pulsed GnRH replacement therapy using the micropump was evaluated in a middle-aged male patient with HH who had experienced the loss of his only child. Relevant literature was also consulted to compare the differences between pulse GnRH treatment and conventional treatment in terms of the development of secondary sexual characteristics, sex hormone levels, sperm production rate, and sperm activity rate in male patient with HH.In this report, a 45-year-old male diagnosed with HH and PES presented with fatigue and decreased libido. The main characteristics included decreased follicle stimulating hormone (FSH) levels of 0.03 mIU/mL, luteinizing hormone (LH) levels of 0.02 mIU/mL, and testosterone (T) levels of 0.72 nmol/L. Magnetic resonance imaging (MRI) revealed an empty sella. Semen analysis showed a small number of normal sperm with reduced motility. During treatment with the micropump pulse GnRH, the patient experienced no side effects and showed improvements in fatigue, reduced libido, sexual urge, anxiety, and feelings of inferiority. LH, FSH, and T levels returned to normal, while sperm activity rate increased to 79.9%. Ultimately, the patient's spouse achieved a natural pregnancy.Pulsed gonadotropin delivery using the micropump demonstrates good efficacy and tolerability, and aligns more closely with the physiological rhythm of GnRH secretion in the human body.

To investigate the association between anti-prothrombin IgM and IgG antibodies and recurrent pregnancy loss (RPL) in a cohort of Lebanese women, and their impact on pregnancy outcomes. This was a retrospective case-control study involving 207 women with RPL and 179 age-matched multiparous controls. Quantitative sandwich ELISA assayed anti-prothrombin IgM and IgG antibodies. Univariate and multivariate logistic regression were employed to assess the risk imparted by anti-prothrombin antibodies, while ROC analysis was used to determine their sensitivity and specificity. Our study revealed that women with RPL had significantly higher serum levels of anti-prothrombin IgM and IgG than controls. Univariate regression analysis demonstrated that elevated anti-prothrombin IgM (OR = 1.13; 95% CI = 1.07, 1.19; P < 0.001) and IgG (OR = 1.05; 95% CI = 1.03, 1.08; P < 0.001) were associated with increased RPL risk. Multivariate analysis confirmed these findings, indicating that anti-prothrombin IgM (aOR = 1.13; 95% CI = 1.05, 1.20; P < 0.001) and IgG (aOR = 1.08; 95% CI = 1.05, 1.11; P < 0.001) are independent risk factors. ROC analysis yielded an AUC of 0.720 for IgM and 0.649 for IgG, underscoring their predictive value and offering hope for improved risk assessment and management of RPL. Elevated levels of anti-prothrombin IgM and IgG are significantly associated with RPL, suggesting an autoimmune component to pregnancy loss. These findings highlight the importance of screening for these antibodies in women with unexplained RPL to guide management and therapeutic strategies.

microRNAs (miRNAs) have a serious and dynamic function in spermatogenesis. These molecules have been recognized as crucial parts of the control of gene activity, and their involvement in the regulation of target genes has been extensively studied. This research aimed to determine the expression of CRISP3 and miR-493-5p, miR-204-5p, and miR-182-5p in the seminal plasma fluid and spermatozoa and to examine the relationship between CRISP3 and the mentioned miRNAs in 57 infertile men with Asthenozoospermia (AZ) (n = 19), Teratoasthenozoospermia (TAZ) (n = 19), and Normozoospermia (NZ) (n = 19). The selection of these three miRNAs, miR-493-5p, miR-204-5p, and miR-182-5p, was conducted using computational prediction algorithms. These miRNAs were nominated as CRISP3-associated miRNAs that can target CRISP3. We performed the quantitative real-time polymerase chain reaction (qRT-PCR) method to determine the levels of the studied miRNA expression. In the following stage, the expression of two protein isoforms of CRISP3, targeted by these miRNAs, was quantified using western blotting. The results demonstrate significant differences in the levels of miR-182-5p, miR-204-5p, miR-493-5p, and CRISP3 isoforms among the patient groups. In TAZ individuals, miR-182-5p and miR-204-5p expression decreased, while miR-493-5p expression increased compared to the control samples. Additionally, significant differences were observed in the expression levels of unglycosylated and glycosylated CRISP3 isoforms between the AZ and NZ groups. Correlation analysis revealed associations between miRNA expression and the expression of CRISP3 isoforms in the patient groups. Additionally, there were correlations between the expression of CRISP3 isoforms and sperm motility and morphology. These results offer valuable insights into the underlying molecular processes associated with male infertility.

Breast and ovarian cancers are significant global health concerns, and understanding their genetic underpinnings is essential for effective prevention and cure. This narrative review provides a comprehensive analysis of studies conducted between 1994 and June 2024, focusing on the link between specific mutations in the breast cancer susceptibility gene 1 (BRCA1) and breast cancer susceptibility gene 2 (BRCA2) and the associated risks of both breast and ovarian cancers. It encompasses the findings of various works, including observational studies and molecular profiling analyses. Conducted on large international cohorts, these studies present compelling evidence of the relationship between different BRCA1 and BRCA2 mutations and the varying risks of breast and ovarian cancer. Furthermore, this review highlights the significance of nonsense-mediated decay mutations and their impact on cancer risk, particularly concerning the age of breast cancer onset. The implications of these findings are far-reaching, offering valuable information for risk assessment and decision-making in managing individuals who carry BRCA1 or BRCA2 mutations. The molecular subtyping profile BluePrint is discussed as a potential tool for enhancing clinical care by aiding the selection of appropriate treatment options, such as endocrine therapy or chemotherapy, based on the tumor's molecular characteristics. In conclusion, we establish a robust link between specific BRCA1 and BRCA2 gene mutations and increased susceptibility to breast and ovarian cancers. These mutations impact cancer onset age and severity, underscoring the need for targeted testing and screening. The current study enhances cancer detection, prevention, and cure strategies.

The prognostic nutritional index (PNI) has emerged as a potential predictor of clinical outcomes in various cancers. However, a quantativetily analysis of its role in endometrial cancer (EC) remains lacking. This meta-analysis aims to evaluate the prognostic value of PNI on the survival outcomes of patients with EC. A comprehensive literature search was conducted in PubMed, EMBASE, Web of Science, Wanfang, and CNKI to identify relevant cohort studies. Studies were included if they provided sufficient data to calculate hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) based on PNI levels. Data extraction and quality assessment were performed independently by two reviewers. Pooled HRs with 95% confidence intervals (CIs) were calculated using a random-effects model to account for heterogeneity. A total of 10 studies, encompassing 3656 patients, met the inclusion criteria. The meta-analysis revealed that a low PNI was significantly associated with poorer OS (HR = 2.01, 95% CI = 1.62-2.49, p < 0.05; I² = 54%) and PFS (HR = 2.75, 95% CI = 1.74-4.33, p < 0.05; I² = 78%) in patients with EC. Subgroup analyses indicated that the prognostic impact of PNI was consistent in studies from Asian and non-Asian countries, and across studies with different ages of the patients, cutoff values of PNI, and follow-up duration (p for subgroup difference all > 0.05). In conclusion, the PNI is a prognostic marker for survival in patients with EC.

There is limited and inconsistent evidence that imply a relationship between ABO blood types and rate of preterm birth (PTB). We aim to examine the association between maternal ABO blood group and PTB rate. A retrospective-study conducted at a university teaching institution on data collected between 2013 and 2019. Women who delivered a viable neonate at ≥ 24 weeks without major malformations were included. Indicated PTBs were excluded. PTB and early PTB were defined as deliveries that occurred < 37 and < 34 weeks respectively. PTB was further divided into 3 subgroups according to etiology: membranes rupture, intact membranes, and placental abruption regardless of membranes' status. The primary outcome was spontaneous PTB rate. Of 19,301 women included, PTB and early PTB rates were 7.3% (1,418/19,301) and 2.3% (440/19,301) respectively. Rates of PTB in blood groups A, B, O, and AB, were 7.3%, 6.9%, 7.5%, and 7.5% respectively (p = 0.68). There was no significant difference according to etiology. Rates of early PTB were also comparable (p = 0.63). After adjustment for demographic and obstetric variables, blood type was associated with increased placental abruption rate among women who had early PTB (p = 0.038). Placental abruption rate was significantly higher in group A (22.5%) compared to group B (14.1%), (adjusted p = 0.04) and group O (14.0%), (adjusted p = 0.01). The rate in group AB was 17.1%, (adjusted p = 0.85). In conclusion, no association was found between a particular blood group and PTB rate. Women with group A, admitted in early PTB, had an increased risk that the underlying etiology was placental abruption.