Machine learning and bioinformatics framework integration reveal potential characteristic genes related to immune cell infiltration in preeclampsia

Introduction: Preeclampsia is a disease that affects both the mother and child, with serious consequences. Screening the characteristic genes of preeclampsia and studying the placental immune microenvironment are expected to explore specific methods for the treatment of preeclampsia and gain an in-depth understanding of the pathological mechanism of preeclampsia.Methods: We screened for differential genes in preeclampsia by using limma package. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, disease ontology enrichment, and gene set enrichment analyses were performed. Analysis and identification of preeclampsia biomarkers were performed by using the least absolute shrinkage and selection operator regression model, support vector machine recursive feature elimination, and random forest algorithm. The CIBERSORT algorithm was used to analyze immune cell infiltration. The characteristic genes were verified by RT-qPCR.Results: We identified 73 differential genes, which mainly involved in reproductive structure and system development, hormone transport, etc. KEGG analysis revealed emphasis on cytokine–cytokine receptor interactions and interleukin-17 signaling pathways. Differentially expressed genes were dominantly concentrated in endocrine system diseases and reproductive system diseases. Our findings suggest that LEP, SASH1, RAB6C, and FLT1 can be used as placental markers for preeclampsia and they are associated with various immune cells.Conclusion: The differentially expressed genes in preeclampsia are related to inflammatory response and other pathways. Characteristic genes, LEP, SASH1, RAB6C, and FLT1 can be used as diagnostic and therapeutic targets for preeclampsia, and they are associated with immune cell infiltration. Our findings contribute to the pathophysiological mechanism exploration of preeclampsia. In the future, the sample size needs to be expanded for data analysis and validation, and the immune cells need to be further validated

The causal association between smoking initiation, alcohol and coffee consumption, and women’s reproductive health: A two-sample Mendelian randomization analysis

Objective: A number of epidemiological studies have demonstrated that smoking initiation and alcohol and coffee consumption were closely related to women’s reproductive health. However, there was still insufficient evidence supporting their direct causality effect.Methods: We utilized two-sample Mendelian randomization (TSMR) analysis with summary datasets from genome-wide association study (GWAS) to investigate the causal relationship between smoking initiation, alcohol and coffee consumption, and women’s reproductive health-related traits. Exposure genetic instruments were used as variants significantly related to traits. The inverse-variance weighted (IVW) method was used as the main analysis approach, and we also performed MR-PRESSO, MR-Egger, weighted median, and weighted mode to supplement the sensitivity test. Then, the horizontal pleiotropy was detected by using MRE intercept and MR-PRESSO methods, and the heterogeneity was assessed using Cochran’s Q statistics.Results: We found evidence that smoking women showed a significant inverse causal association with the sex hormone-binding globulin (SHBG) levels (corrected β = −0.033, p = 9.05E-06) and age at menopause (corrected β = −0.477, p = 6.60E-09) and a potential positive correlation with the total testosterone (TT) levels (corrected β = 0.033, p = 1.01E-02). In addition, there was suggestive evidence for the alcohol drinking effect on the elevated TT levels (corrected β = 0.117, p = 5.93E-03) and earlier age at menopause (corrected β = −0.502, p = 4.14E-02) among women, while coffee consumption might decrease the female SHBG levels (corrected β = −0.034, p = 1.33E-03).Conclusion: Our findings suggested that smoking in women significantly decreased their SHBG concentration, promoted earlier menopause, and possibly reduced the TT levels. Alcohol drinking had a potential effect on female higher TT levels and earlier menopause, while coffee consumption might lead to lower female SHBG levels

Methylation levels at IGF2 and GNAS DMRs in infants born to preeclamptic pregnancies

BACKGROUND: Offspring of pregnancy complicated with preeclampsia are at high risk for hypertension, stroke and possibly obesity. The mechanisms behind the association of intrauterine exposure to preeclampsia and high risk of health problems in the later life remain largely unknown. The aims of the current investigation were to determine the changes in DNA methylation at IGF2 and GNAS DMR in offspring of preeclamptic pregnancy and to explore the possible mechanisms underlying the association between maternal preeclampsia and high risk for health problems in the later life of their offspring. RESULTS: Umbilical cord blood was taken from infants born to women of preeclampsia (n=56), gestational hypertension (n=23) and normal pregnancy (n=81). DNA methylation levels of IGF2 and GNAS DMR were determined by Massarray quantitative methylation analysis. Methylation levels at IGF2 DMR were significantly lower in preeclampsia than normal pregnancy. The average methylation level at IGF2 DMR was significantly correlated with preeclampsia even after birth weight, maternal age, gestational age at delivery and fetal gender were adjusted. The difference in methylation level was not significantly different between mild and severe preeclampsia. The methylation level at GNAS DMR was not significantly correlated with birth weight, maternal age, gestational age at delivery, fetal gender, preeclampsia or gestational hypertension. CONCLUSIONS: We concluded preeclampsia induced a decrease in methylation level at IGF 2 DMR, and this might be among the mechanisms behind the association between intrauterine exposure to preeclampsia and high risk for metabolic diseases in the later life of the infants

Ignored adult primary hypothyroidism presenting chiefly with persistent ovarian cysts: a need for increased awareness

<p>Abstract</p> <p>Background</p> <p>Ovarian cysts are a common cause for gynecological surgery. However, some cysts are a direct result of endocrine disorders and do not require surgery. This report describes an unusual case in which persistent ovarian cysts are associated with primary hypothyroidism in a young woman. The data were collected by history-taking, physical examination, laboratory tests, ultrasound, magnetic resonance imaging and a histo-pathological study. In addition, the exons of the gene encoding the human follicle-stimulating hormone receptor were sequenced.</p> <p>Discussion</p> <p>The patient had markedly elevated levels of thyroid-stimulating hormone and follicle-stimulating hormone and an enlarged pituitary gland. After treatment with thyroid hormone replacement, regression of the enlarged pituitary and the ovarian cysts was observed. The possible mechanisms of the pathophysiology are discussed below.</p> <p>Summary</p> <p>It is necessary to consider hypothyroidism and other endocrine disorders in the differential diagnosis of adult patients with ovarian multiple cyst formation in order to prevent inadvertent ovarian surgery.</p

Neurogenesis Potential Evaluation and Transcriptome Analysis of Fetal Hypothalamic Neural Stem/Progenitor Cells With Prenatal High Estradiol Exposure

High maternal estradiol is reported to induce metabolic disorders by modulating hypothalamic gene expression in offspring. Since neurogenesis plays a crucial role during hypothalamus development, we explored whether prenatal high estradiol exposure (HE) affects proliferation and differentiation of fetal hypothalamic neural stem/progenitor cells (NSC/NPCs) in mice and performed RNA sequencing to identify the critical genes involved. NSC/NPCs in HE mice presented attenuated cell proliferation but increased neuronal differentiation in vitro compared with control (NC) cells. Gene set enrichment analysis of mRNA profiles indicated that genes downregulated in HE NSC/NPCs were enriched in neurogenesis-related Gene Ontology (GO) terms, while genes upregulated in HE NSC/NPCs were enriched in response to estradiol. Protein-protein interaction analysis of genes with core enrichment in GO terms of neurogenesis and response to estradiol identified 10 Hub mRNAs, among which three were potentially correlated with six differentially expressed (DE) lncRNAs based on lncRNA profiling and co-expression analysis. These findings offer important insights into developmental modifications in hypothalamic NSC/NPCs and may provide new clues for further investigation on maternal environment programmed neural development disorders

Effective noninvasive zygosity determination by maternal plasma target region sequencing

Background: Currently very few noninvasive molecular genetic approaches are available to determine zygosity for twin pregnancies in clinical laboratories. This study aimed to develop a novel method to determine zygosity by using maternal plasma target region sequencing. Methods: We constructed a statistic model to calculate the possibility of each zygosity type using likelihood ratios (Li) and empirical dynamic thresholds targeting at 4,524 single nucleotide polymorphisms (SNPs) loci on 22 autosomes. Then two dizygotic (DZ) twin pregnancies, two monozygotic (MZ) twin pregnancies and two singletons were recruited to evaluate the performance of our novel method. Finally we estimated the sensitivity and specificity of the model in silico under different cell-free fetal DNA (cff-DNA) concentration and sequence depth. Results/Conclusions: We obtained 8.90 Gbp sequencing data on average for six clinical samples. Two samples were classified as DZ with L values of 1.891 and 1.554, higher than the dynamic DZ cut-off values of 1.162 and 1.172, respectively. Another two samples were judged as MZ with 0.763 and 0.784 of L values, lower than the MZ cut-off values of 0.903 and 0.918. And the rest two singleton samples were regarded as MZ twins, with L values of 0.639 and 0.757, lower than the MZ cut-off values of 0.921 and 0.799. In silico, the estimated sensitivity of our noninvasive zygosity determination was 99.90% under 10% total cff-DNA concentration with 2 Gbp sequence data. As the cff-DNA concentration increased to 15%, the specificity was as high as 97% with 3.50 Gbp sequence data, much higher than 80% with 10% cff-DNA concentration. Significance: This study presents the feasibility to noninvasively determine zygosity of twin pregnancy using target region sequencing, and illustrates the sensitivity and specificity under various detecting condition. Our method can act as an alternative approach for zygosity determination of twin pregnancies in clinical practice.Multidisciplinary SciencesSCI(E)2ARTICLE6null

Chinese Medicinal Herbs in Relieving Perimenopausal Depression: A Randomized, Controlled Trial

Abstract Objective: To explore the effects of GengNianLe (GNL, also called perimenopausal depression relieving formula), a defined formula of Chinese medicinal herbs in relieving perimenopausal depression in Chinese women. Methods : Between September 2004 and April 2008, 47 Chinese women were randomized into a GNL group (n ϭ 21) and a control group which received tibolone (n ϭ 26) using a randomization chart. Depression was rated with the 24-item Hamilton Depression Scale (HAMD). The serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E 2 ) were detected before and after the treatment. Results: After 12 weeks of treatment, HAMD scores in both groups decreased significantly (p Ͻ 0.05) with no significant difference between the groups (p Ͼ 0.05). The levels of FSH decreased significantly and the level of E 2 increased significantly in both groups, and they changed more in the control group. No side-effect of treatment was reported in either group during treatment. Conclusions: The Chinese medicinal formula GNL showed promise in relieving perimenopausal depression and merits further study. 9

Research advances of gamete and embryo-fetal origins of adult diseases

The Development Origins of Health and Disease (DOHaD) theory suggests that adverse environmental factors in early life contribute to the development of chronic disease in adulthood. Compared to the intrauterine developmental period of the embryo and fetus, gametes take decades to develop and mature, and are more susceptible to potential damage. Changes in the gametes can be further transmitted to the offspring, leading to an increased risk of congenital anomalies and chronic adult disease in them, and intergenerational transmission effects can exist. Epigenetic modification refers to the regulation of gene expression without altering the nucleotide sequence, and the proposed doctrine offers the possibility of exploring the mechanisms of developmental-derived diseases. This paper summarizes the research progress of the gamete and embryo-fetal origins of diseases, and illustrates the important role of epigenetic mechanisms in this regard, and further emphasizes the importance of health interventions before conception and early in life to shift the primary prevention of diseases to the gametogenesis and intrauterine development of embryos and fetuses