Background: To determine if overweight/obese pregnant women have altered microRNA expression patterns in fetal umbilical cord blood that may affect the development of offspring. Methods: Umbilical cord blood samples were obtained from the fetuses of 34 overweight/obese and 32 normal-weight women after delivery. Next generation sequencing (NGS) analyzed their miRNA expression patterns. miRanda and TargetScan databases were used to predict the miRNAs’ target genes followed by analyses of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to perform function grouping and pathway analyses. qRT-PCR verified the identity of differentially expressed miRNAs that were revealed in the NGS results. Results: There was a positive correlation between newborn body weight and pregestational BMI of pregnant individuals (r = 0.48, P < 0.001). One hundred and eight miRNAs were differentially expressed between the normal and overweight/obese groups, which target genes were enriched in the metabolic pathway. Five C19MC miRNAs (miR-516a-5p, miR-516b-5p, miR-520a-3p, miR-1323, miR-523-5p) were upregulated in the overweight/obese group. Target enrichment analysis suggests their involvement in post-embryonic development, lipid and glucose homeostasis, T cell differentiation and nervous system development. Conclusions: C19MC miRNA expression upregulation in the fetal circulation during the gestation of overweight/obese pregnant women may contribute to altered multisystem metabolic pathway development in their offspring.

Background: Over the past few decades, global maternal obesity prevalence has rapidly increased. This condition may induce long-lasting pathophysiological effects on either fetal or infant health that could be attributable to unknown unique changes in the umbilical blood composition. Methods: A total of 34 overweight/obese and 32 normal-weight pregnant women were recruited. Fifteen umbilical blood samples including 8 overweight/obese subjects and 7 normal weight women were sequenced using Targeted Bisulfite Sequencing technology to detect the average methylation level of cytosine and identify the differentially methylated region (DMR). GO and KEGG analyses were then employed to perform pathway enrichment analysis of DMR-related genes and promoters. Moreover, the mRNA levels of methylation-related genes histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) were characterized in the samples obtained from these two groups. Results: Average methylated cytosine levels in both the CpG islands (CGI) and promoter significantly decreased in overweight/obese groups. A total of 1669 DMRs exhibited differences in their DNA methylation status between the overweight/obese and control groups. GO and KEGG analyses revealed that DMR-related genes and promoters were enriched in the metabolism, cancer and cardiomyopathy signaling pathways. Furthermore, the HDACs and DNMTs mRNA levels trended to decline in overweight/obese groups. Conclusions: Decreased methylated cytosine levels in overweight/obese women induce the gene expression activity at a higher level than in the control group. DMRs between these two groups in the fetal blood may contribute to the changes in gene transcription that underlie the increased risk of metabolic disorders, cancers and cardiomyopathy in their offspring.

Cervical cancer (CESC) is the fourth most common and death-causing gynecological cancer, mostly induced by infection of human papillomavirus (HPV). Multiple components of the tumor microenvironment (TME), such as tumor infiltrating immune cells, could be targets of immunotherapy for HPV-related CESC. However, little is known about the TME of CESC until now. Here, we aimed to uncover the pathogenesis as well as to identify novel biomarkers to predict prognosis and immunotherapy efficacy for CESC. Combining the transcriptomic data and clinical characteristics, we identified differentially expressed genes in CESC samples from TCGA database by comparing the two groups with different ImmuneScore and StromalScore. Next, we detected ten key genes based on the PPI network and survival analyses with the univariate Cox regression model. Thereafter, we focused on CD3G, the only gene exhibiting increased RNA and protein expression in tumors by multiple analyses. Higher CD3G expression was associated with better survival; and it was also significantly associated with immune-related pathways through GSEA analysis. Furthermore, we found that CD3G expression was correlated with 16 types of TICs. Single cell RNA-sequencing data of CD3G in lymphocytes subgroup indicated its possible role in HPV defense. Hence, CD3G might be a novel biomarker in prognosis and immunotherapy for CESC patients.

Premature ovarian insufficiency (POI) is characterized by follicular development failure or follicular dysplasia, therefore causing the lack of normal ovarian function before 40 years of age. Trimethylamine N-oxide (TMAO) is a metabolite of high choline diet rich in red meat and directly associated with gut microbiota. Correlation of TMAO level with female fertility decline has been shown; however, its mechanism is largely unknown. To unveil the mechanism by which TMAO affects female reproductive function, we established a TMAO-treated mouse model which exhibited the pathological manifestations of POI including increased follicle-stimulating hormone and luteinizing hormone levels, decreased estradiol and anti-Müllerian hormone levels, reduced growing and mature follicles, increased atretic follicles, and decreased fertility. Meanwhile, these mice showed an increased apoptosis ratio and damaged mitochondrial function in granulosa cells, the nursing and supporting cells for oocyte development. Moreover, TMAO treatment significantly elevated oxidative stress and reduced antioxidative capacity in granulosa cells, whereas the antioxidants N-acetylcysteine alleviated such detriment. Mechanism investigation demonstrated that TMAO treatment up-regulated phosphatase and tensin homolog expression levels in granulosa cells, thereby inhibiting the phosphorylation of AKT and subsequently causing high expression of BCL-2-associated X protein, a key molecule in the mitochondria pathway, leading to increased cell apoptosis. Our findings documented the pathological mechanism of TMAO-induced POI, which may provide a potential target for curing POI clinically.

Background: Cervical cancer remains a leading cause of morbidity and mortality among women, disproportionately affecting low- and middle-income countries (LMICs). We sought to: (1) characterize temporal and geographic patterns of cervical cancer burden (1990–2021), with a focus on age-related differences; (2) identify attributable risk factors for cervical cancer, emphasizing the impact of HPV vaccination; (3) forecast cervical cancer burden through 2050. Methods: We combined: (a) age-specific female population estimates (UN World Population Prospects 2024), (b) cervical cancer incidence, mortality and disability-adjusted life-years (DALYs) from Global Burden of Disease (GBD) 2021, and (c) HPV vaccination coverage (WHO). We calculated age-standardized incidence (ASIR), mortality (ASMR), and DALYs rate (ASDR) using the WHO world standard population. Stratified analyses were performed by Socio-demographic Index (SDI) category and 5-year age groups. Future burdens were projected under current intervention coverage. Findings: From 1990 to 2021, global ASIR, ASMR and ASDR declined by 15, 31 and 32%, respectively, yet absolute cases rose due to population growth and ageing. The greatest burdens remain in low-SDI regions, especially Southern Sub-Saharan Africa, which uniquely saw rising ASIR and ASMR. Women aged 55–59 bear the highest rates, while young women (15–39) experienced a small but significant incidence increase in 92 countries (notably Russia, Brazil and China). Unsafe sex and smoking accounted for the majority of cervical cancer DALYs. A profound disparity in HPV vaccine coverage persists between high- and low-SDI regions. Projections to 2050 indicate a continued rise in absolute case numbers, despite modest declines in age-standardized rates (ASRs). Conclusion: While ASRs show improvement, the growing absolute burden and profound geographic inequities highlight an urgent public health challenge. Accelerating the scale-up of HPV vaccination, screening, and other preventive measures, with a strategic focus on LMICs, is critical to achieving the WHO elimination targets for cervical cancer.