Genetically predicted serum testosterone and risk of gynecological disorders: a Mendelian randomization study.

Background: Testosterone plays a key role in women, but the associations of serum testosterone level with gynecological disorders risk are inconclusive in observational studies. Methods: We leveraged public genome-wide association studies to analyze the effects of four testosterone related exposure factors on nine gynecological diseases. Causal estimates were calculated by inverse variance-weighted (IVW), MR-Egger and weighted median methods. The heterogeneity test was performed on the obtained data through Cochrane's Q value, and the horizontal pleiotropy test was performed on the data through MR-Egger intercept and MR-PRESSO methods. "mRnd" online analysis tool was used to evaluate the statistical power of MR estimates. Results: The results showed that total testosterone and bioavailable testosterone were protective factors for ovarian cancer (odds ratio (OR) = 0.885, P = 0.012; OR = 0.871, P = 0.005) and endometriosis (OR = 0.805, P = 0.020; OR = 0.842, P = 0.028) but were risk factors for endometrial cancer (OR = 1.549, P < 0.001; OR = 1.499, P < 0.001) and polycystic ovary syndrome (PCOS) (OR = 1.606, P = 0.019; OR = 1.637, P = 0.017). dehydroepiandrosterone sulfate (DHEAS) is a protective factor against endometriosis (OR = 0.840, P = 0.016) and premature ovarian failure (POF) (OR = 0.461, P = 0.046) and a risk factor for endometrial cancer (OR= 1.788, P < 0.001) and PCOS (OR= 1.970, P = 0.014). sex hormone-binding globulin (SHBG) is a protective factor against endometrial cancer (OR = 0.823, P < 0.001) and PCOS (OR = 0.715, P = 0.031). Conclusion: Our analysis suggested causal associations between serum testosterone level and ovarian cancer, endometrial cancer, endometriosis, PCOS, POF.

The Role of ApoE Expression and Variability of Its Glycosylation in Human Reproductive Health in the Light of Current Information.

Apolipoprotein E (ApoE), a 34-kDa glycoprotein, as part of the high-density lipoprotein (HDL), has antioxidant, anti-inflammatory and antiatherogenic properties. The variability of ApoE expression in the course of some female fertility disorders (endometriosis, POCS), and other gynecological pathologies such as breast cancer, choriocarcinoma, endometrial adenocarcinoma/hyperplasia and ovarian cancer confirm the multidirectional biological function of ApoE, but the mechanisms of its action are not fully understood. It is also worth taking a closer look at the associations between ApoE expression, the type of its genotype and male fertility disorders. Another important issue is the variability of ApoE glycosylation. It is documented that the profile and degree of ApoE glycosylation varies depending on where it occurs, the type of body fluid and the place of its synthesis in the human body. Alterations in ApoE glycosylation have been observed in the course of diseases such as preeclampsia or breast cancer, but little is known about the characteristics of ApoE glycans analyzed in human seminal and blood serum/plasma in the context of male reproductive health. A deeper analysis of ApoE glycosylation in the context of female and male fertility will both enable us to broaden our knowledge of the biochemical and cellular mechanisms in which glycans participate, having a direct or indirect relationship with the fertilization process, and also give us a chance of contributing to the enrichment of the diagnostic panel in infertile women and men, which is particularly important in procedures involved in assisted reproductive techniques. Moreover, understanding the mechanisms of glycoprotein glycosylation related to the course of various diseases and conditions, including infertility, and the interactions between glycans and their specific ligands may provide us with an opportunity to interfere with their course and thus develop new therapeutic strategies. This brief overview details some of the recent advances, mainly from the last decade, in understanding the associations between ApoE expression and some female and male fertility problems, as well as selected female gynecological diseases and male reproductive tract disorders. We were also interested in how ApoE glycosylation changes influence biological processes in the human body, with special attention to human fertility.

The Role of microRNA Let-7d in Female Malignancies and Diseases of the Female Reproductive Tract.

microRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level. Let-7d is a microRNA of the conserved let-7 family that is dysregulated in female malignancies including breast cancer, ovarian cancer, endometrial cancer, and cervical cancer. Moreover, a dysregulation is observed in endometriosis and pregnancy-associated diseases such as preeclampsia and fetal growth restriction. Let-7d expression is regulated by cytokines and steroids, involving transcriptional regulation by OCT4, MYC and p53, as well as posttranscriptional regulation via LIN28 and ADAR. By downregulating a wide range of relevant mRNA targets, let-7d affects cellular processes that drive disease progression such as cell proliferation, apoptosis (resistance), angiogenesis and immune cell function. In an oncological context, let-7d has a tumor-suppressive function, although some of its functions are context-dependent. Notably, its expression is associated with improved therapeutic responses to chemotherapy in breast and ovarian cancer. Studies in mouse models have furthermore revealed important roles in uterine development and function, with implications for obstetric diseases. Apart from a possible utility as a diagnostic blood-based biomarker, pharmacological modulation of let-7d emerges as a promising therapeutic concept in a variety of female disease conditions.

WNT4 Balances Development vs Disease in Gynecologic Tissues and Women's Health.

The WNT family of proteins is crucial in numerous developmental pathways and tissue homeostasis. WNT4, in particular, is uniquely implicated in the development of the female phenotype in the fetus, and in the maintenance of müllerian and reproductive tissues. WNT4 dysfunction or dysregulation can drive sex-reversal syndromes, highlighting the key role of WNT4 in sex determination. WNT4 is also critical in gynecologic pathologies later in life, including several cancers, uterine fibroids, endometriosis, and infertility. The role of WNT4 in normal decidualization, implantation, and gestation is being increasingly appreciated, while aberrant activation of WNT4 signaling is being linked both to gynecologic and breast cancers. Notably, single-nucleotide polymorphisms (SNPs) at the WNT4 gene locus are strongly associated with these pathologies and may functionally link estrogen and estrogen receptor signaling to upregulation and activation of WNT4 signaling. Importantly, in each of these developmental and disease states, WNT4 gene expression and downstream WNT4 signaling are regulated and executed by myriad tissue-specific pathways. Here, we review the roles of WNT4 in women's health with a focus on sex development, and gynecologic and breast pathologies, and our understanding of how WNT4 signaling is controlled in these contexts. Defining WNT4 functions provides a unique opportunity to link sex-specific signaling pathways to women's health and disease.

Biogenesis and functions of circular RNAs and their role in diseases of the female reproductive system.

A member of the newly discovered RNA family, circular RNA (circRNA) is considered as the intermediate product of by-product splicing or abnormal RNA splicing. With the development of RNA sequencing, circRNA has recently drawn research interest. CircRNA exhibits stability, species conservatism, and tissue cell specificity. It acts as a miRNA sponge in the circRNA-microRNA (miRNA-mRNA axis, which can regulate gene transcription and protein translation. Studies have confirmed that circRNA is ubiquitous in eukaryotic cells, which play an important role in the regulation of human gene expression and participate in the occurrence and development of various human diseases. CircRNA may be closely related to the occurrence and development of female reproductive system diseases. By analyzing the biological functions and mechanism of circRNA, we find that circRNA has certain development prospects as biomarkers of the female reproductive system diseases. The production and degradation of circRNA, biological functions, and their association with the occurrence of diseases of female reproductive system are reviewed in this article.

Report of the National Cancer Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development-sponsored workshop: gynecology and women's health-benign conditions and cancer.

The Division of Cancer Prevention and the Division of Cancer Biology at the National Cancer Institute and the Gynecologic Health and Disease Branch in the National Institute of Child Health and Human Development organized a workshop in April 2019 to explore current insights into the progression of gynecologic cancers from benign conditions. Working groups were formed based on 3 gynecologic disease types: (1) Endometriosis or Endometrial Cancer and Endometrial-Associated Ovarian Cancer, (2) Uterine Fibroids (Leiomyoma) or Leiomyosarcoma, and (3) Adenomyosis or Adenocarcinoma. In this report, we highlight the key questions and current challenges that emerged from the working group discussions and present potential research opportunities that may advance our understanding of the progression of gynecologic benign conditions to cancer.

Gynecologic and reproductive health in patients with pathogenic germline variants in DICER1.

OBJECTIVE: Germline pathogenic variation in DICER1 underlies a tumor-predisposition disorder with increased risk for cervical embryonal rhabdomyosarcoma and ovarian sex-cord stromal tumors, particularly Sertoli-Leydig cell tumors. The gynecologic and reproductive health of these females has not yet been described. METHODS: All female subjects recruited from November 2011 to July 2018 participating in an epidemiologic study of families with pathogenic DICER1 germline variation were included in this cross-sectional analysis. Participant evaluation included obstetric-gynecologic history, physical examination, hormone testing, pelvic ultrasound and record review. RESULTS: Of 64 females aged 2-72 years, fifteen underwent treatment for pleuropulmonary blastoma as children and three were treated for cervical embryonal rhabdomyosarcoma. Of nine patients reporting a history of ovarian tumors, all presented with virilization or amenorrhea; eight occurred in adolescence. Post-pubertal females with no history of ovarian tumors experienced normal pubertal development, reported regular menstrual cycles, were fertile and underwent natural menopause at median age of 52 years. Thirty-two of 33 women who tried to conceive successfully delivered liveborn children. Of these 32, 10 experienced pregnancy-related thyroid enlargement resulting in thyroidectomy within one year of pregnancy; nine others had undergone pre-pregnancy thyroidectomy. CONCLUSION: In these DICER1-carrier females, DICER1-related gynecological tumors occurred during childhood or adolescence in some after which women generally experienced healthy reproductive lives. Individual education and screening for these tumors is warranted. The high rate of DICER1-related multinodular goiter resulting in pre- and post-pregnancy thyroidectomy underscores the importance of thyroid monitoring during pregnancy to ensure maternal and fetal wellbeing.

Evaluation of COLIA1-1997 G/T polymorphism as a related factor to genital prolapse.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse has a multifactorial etiology. There is increasing evidence that genetic factors greatly impact its development. This study aimed to evaluate the possible relation of the collagenous polymorphism -1997 G/T with genital prolapse in Brazilian women. METHODS: A cohort study of 180 women with stage 0 or I (group A) pelvic organ prolapse disorder and 112 women with stage III or IV (group B) was conducted. Blood DNA was isolated, and the -1997 G/T polymorphism was identified by amplifying a region of the COLIA1 gene starting prior to the protein's coding sequence. RESULTS: No significant difference in the prevalence of genotypes TG and TT was found between groups (p = 0.67); differences were not found even when patients were grouped by the presence of 0 or ≥ 1 polymorphic alleles (p = 0.46). Age and home birth were found to be independent risk factors for prolapse. CONCLUSIONS: Our study could not find any association between the -1997G/T polymorphism and genital prolapse in Brazilian women.

Circular RNAs in gynecological disease: promising biomarkers and diagnostic targets.

Circular RNAs (circRNAs) are a category of RNA molecules with covalently closed circles lacking both a 5' cap and a 3' tail. In recent years, circRNAs have attracted much attention and become a research hotspot of the RNA field following miRNAs and lncRNAs. CircRNAs exhibit tissue specificity, structural stability, and evolutionary conservation. Although the biological effects of circRNAs are still underestimated, many studies have shown that circRNAs have functions including regulation of transcription, translation into proteins and miRNA sponges. In this review, we briefly described the biogenesis and function of circRNAs and present circular transcripts in gynecological disease.

Hazardous effects of chemical pesticides on human health-Cancer and other associated disorders.

Poisoning from pesticides is a global public health problem and accounts for nearly 300,000 deaths worldwide every year. Exposure to pesticides is inevitable; there are different modes through which humans get exposed to pesticides. The mode of exposure is an important factor as it also signifies the concentration of pesticides exposure. Pesticides are used extensively in agricultural and domestic settings. These chemicals are believed to cause many disorders in humans and wildlife. Research from past few decades has tried to answer the associated mechanism of action of pesticides in conjunction with their harmful effects. This perspective considers the past and present research in the field of pesticides and associated disorders. We have reviewed the most common diseases including cancer which are associated with pesticides. Pesticides have shown to be involved in the pathogenesis of Parkinson's and Alzheimer's diseases as well as various disorders of the respiratory and reproductive tracts. Oxidative stress caused by pesticides is an important mechanism through which many of the pesticides exert their harmful effects. Oxidative stress is known to cause DNA damage which in turn may cause malignancies and other disorders. Many pesticides have shown to modulate the gene expression at the level of non-coding RNAs, histone deacetylases, DNA methylation patterns suggesting their role in epigenetics.

Hiperandrogenismo transitorio en 2 gemelas prematuras expuestas a antirretrovirales / Transient hyperandrogenism in 2 preterm twins with exposure to antiretrovirals

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Combined Effect of the PGR +331C > T, CYP17A1 -34A > G and CYP19A1 1531G > A Polymorphisms on the Risk of Developing Endometriosis.

Purpose To evaluate the magnitude of the association of the polymorphisms of the genes PGR, CYP17A1 and CYP19A1 in the development of endometriosis. Methods This is a retrospective case-control study involving 161 women with endometriosis (cases) and 179 controls. The polymorphisms were genotyped by real-time polymerase chain reaction using the TaqMan system. The association of the polymorphisms with endometriosis was evaluated using the multivariate logistic regression. Results The endometriosis patients were significantly younger than the controls (36.0 ± 7.3 versus 38.0 ± 8.5 respectively, p = 0.023), and they had a lower body mass index (26.3 ± 4.8 versus 27.9 ± 5.7 respectively, p = 0.006), higher average duration of the menstrual flow (7.4 ± 4.9 versus 6.1 ± 4.4 days respectively, p = 0.03), and lower average time intervals between menstrual periods (25.2 ± 9.6 versus 27.5 ± 11.1 days respectively, p = 0.05). A higher prevalence of symptoms of dysmenorrhea, dyspareunia, chronic pelvic pain, infertility and intestinal or urinary changes was observed in the case group when compared with the control group. The interval between the onset of symptoms and the definitive diagnosis of endometriosis was 5.2 ± 6.9 years. When comparing both groups, significant differences were not observed in the allelic and genotypic frequencies of the polymorphisms PGR +331C > T, CYP17A1 -34A > G and CYP19A1 1531G > A, even when considering the symptoms, classification and stage of the endometriosis. The combined genotype PGR +331TT/CYP17A1 -34AA/CYP19A11531AA is positively associated with endometriosis (odds ratio [OR] = 1.72; 95% confidence interval [95%CI] = 1.09-2.72). Conclusions The combined analysis of the polymorphisms PGR-CYP17A1-CYP19A1 suggests a gene-gene interaction in the susceptibility to endometriosis. These results may contribute to the identification of biomarkers for the diagnosis and/or prognosis of the disease and of possible molecular targets for individualized treatments.

Objetivo Avaliar a magnitude de associação de polimorfismos nos genes PGR, CYP17A1 e CYP19A1 no desenvolvimento da endometriose. Métodos Este é um estudo retrospectivo do tipo caso-controle, envolvendo 161 mulheres com endometriose (casos) e 179 controles. Os polimorfismos foram genotipados pela reação em cadeia da polimerase em tempo real utilizando o sistema TaqMan. A associação dos polimorfismos estudados com a endometriose foi avaliada pela regressão logística multivariada. Resultados As pacientes com endometriose eram significativamente mais jovens do que os controles (36,0 ± 7,3 versus 38,0 ± 8,5, respectivamente, p = 0,023), apresentaram um índice de massa corporal menor (26,3 ± 4,8 versus 27,9 ± 5,7, respectivamente, p = 0,006), maior tempo médio de duração do fluxo menstrual (7,4 ± 4,9 versus 6,1 ± 4,4 dias, respectivamente, p = 0,03) e menor tempo médio do intervalo entre as menstruações (25,2 ± 9,6 versus 27,5 ± 11,1 dias, respectivamente, p = 0,05). Uma maior prevalência dos sintomas de dismenorreia, dispareunia, dor pélvica crônica, infertilidade, alterações intestinais e urinárias foi observada no grupo casos comparado ao grupo controle. O tempo médio entre o início dos sintomas e o diagnóstico definitivo de endometriose foi de 5,2 ± 6,9 anos. Comparando os dois grupos, não foram observadas diferenças significativas nas frequências alélicas e genotípicas dos polimorfismos PGR +331C > T, CYP17A1 -34A > G e CYP19A1 1531G > A, e nem considerando os sintomas, a classificação e o estadiamento da endometriose. O genótipo combinado PGR +331TT/CYP17A1 -34AA/CYP19A11531AA está associado positivamente com a endometriose (razão de possibilidades [RP] = 1,72; intervalo de confiança de 95% [IC95%] = 1,09­2,72). Conclusões A análise combinada dos polimorfismos PGR-CYP17A1-CYP19A1 sugere uma interação gene-gene na susceptibilidade à endometriose. Estes resultados podem contribuir para a identificação de biomarcadores para o diagnóstico e/ou prognóstico da doença, assim como de possíveis alvos moleculares para um tratamento individualizado.

Combined Effect of the PGR + 331C > T, CYP17A1 -34A > G and CYP19A1 1531G > A Polymorphisms on the Risk of Developing Endometriosis / Efeito combinado dos polimorfismos PGR + 331C > T, CYP17A1 -34A > G e CYP19A1 1531G > A no risco de desenvolvimento da endometriose

Abstract Purpose To evaluate the magnitude of the association of the polymorphisms of the genes PGR, CYP17A1 and CYP19A1 in the development of endometriosis. Methods This is a retrospective case-control study involving 161 women with endometriosis (cases) and 179 controls. The polymorphisms were genotyped by real-time polymerase chain reaction using the TaqMan system. The association of the polymorphisms with endometriosis was evaluated using the multivariate logistic regression. Results The endometriosis patients were significantly younger than the controls (36.0±7.3 versus 38.0±8.5 respectively, p = 0.023), and they had a lower body mass index (26.3±4.8 versus 27.9±5.7 respectively, p = 0.006), higher average duration of the menstrual flow (7.4±4.9 versus 6.1±4.4 days respectively, p = 0.03), and lower average time intervals between menstrual periods (25.2±9.6 versus 27.5±11.1 days respectively, p = 0.05). A higher prevalence of symptoms of dysmenorrhea, dyspareunia, chronic pelvic pain, infertility and intestinal or urinary changes was observed in the case group when compared with the control group. The interval between the onset of symptoms and the definitive diagnosis of endometriosis was 5.2±6.9 years. When comparing both groups, significant differences were not observed in the allelic and genotypic frequencies of the polymorphisms PGR + 331C > T, CYP17A1 -34A > G and CYP19A1 1531G > A, even when considering the symptoms, classification and stage of the endometriosis. The combined genotype PGR + 331TT/CYP17A1 -34AA/CYP19A11531AA is positively associated with endometriosis (odds ratio [OR] = 1.72; 95% confidence interval [95%CI] = 1.09-2.72). Conclusions The combined analysis of the polymorphisms PGR-CYP17A1-CYP19A1 suggests a gene-gene interaction in the susceptibility to endometriosis. These results may contribute to the identification of biomarkers for the diagnosis and/or prognosis of the disease and of possible molecular targets for individualized treatments.

Resumo Objetivo Avaliar a magnitude de associação de polimorfismos nos genes PGR, CYP17A1 e CYP19A1 no desenvolvimento da endometriose. Métodos Este é um estudo retrospectivo do tipo caso-controle, envolvendo 161 mulheres com endometriose (casos) e 179 controles. Os polimorfismos foram genotipados pela reação em cadeia da polimerase em tempo real utilizando o sistema TaqMan. A associação dos polimorfismos estudados com a endometriose foi avaliada pela regressão logística multivariada. Resultados As pacientes com endometriose eram significativamente mais jovens do que os controles (36,0±7,3 versus 38,0±8,5, respectivamente, p = 0,023), apresentaram um índice de massa corporal menor (26,3±4,8 versus 27,9±5,7, respectivamente, p = 0,006), maior tempo médio de duração do fluxo menstrual (7,4±4,9 versus 6,1±4,4 dias, respectivamente, p = 0,03) e menor tempo médio do intervalo entre as menstruações (25,2±9,6 versus 27,5±11,1 dias, respectivamente, p = 0,05). Uma maior prevalência dos sintomas de dismenorreia, dispareunia, dor pélvica crônica, infertilidade, alterações intestinais e urinárias foi observada no grupo casos comparado ao grupo controle. O tempo médio entre o início dos sintomas e o diagnóstico definitivo de endometriose foi de 5,2±6,9 anos. Comparando os dois grupos, não foram observadas diferenças significativas nas frequências alélicas e genotípicas dos polimorfismos PGR + 331C > T, CYP17A1 -34A > G e CYP19A1 1531G > A, e nem considerando os sintomas, a classificação e o estadiamento da endometriose. O genótipo combinado PGR + 331TT/CYP17A1 -34AA/CYP19A11531AA está associado positivamente com a endometriose (razão de possibilidades [RP] = 1,72; intervalo de confiança de 95% [IC95%] = 1,09-2,72). Conclusões A análise combinada dos polimorfismos PGR-CYP17A1-CYP19A1 sugere uma interação gene-gene na susceptibilidade à endometriose. Estes resultados podem contribuir para a identificação de biomarcadores para o diagnóstico e/ou prognóstico da doença, assim como de possíveis alvos moleculares para um tratamento individualizado.

Phosphorylation of HSF1 at serine 326 residue is related to the maintenance of gynecologic cancer stem cells through expression of HSP27.

Cancer stem-like cells (CSCs)/ cancer-initiating cells (CICs) are defined by their higher tumor-initiating ability, self-renewal capacity and differentiation capacity. CSCs/CICs are resistant to several therapies including chemotherapy and radiotherapy. CSCs/CICs thus are thought to be responsible for recurrence and distant metastasis, and elucidation of the molecular mechanisms of CSCs/CICs are essential to design CSC/CIC-targeting therapy. In this study, we analyzed the molecular aspects of gynecological CSCs/CICs. Gynecological CSCs/CICs were isolated as ALDH1high cell by Aldefluor assay. The gene expression profile of CSCs/CICs revealed that several genes related to stress responses are preferentially expressed in gynecological CSCs/CICs. Among the stress response genes, a small heat shock protein HSP27 has a role in the maintenance of gynecological CSCs/CICs. The upstream transcription factor of HSP27, heat shock factior-1 (HSF1) was activated by phosphorylation at serine 326 residue (pSer326) in CSCs/CICs, and phosphorylation at serine 326 residue is essential for induction of HSP27. Immunohistochemical staining using clinical ovarian cancer samples revealed that higher expressions of HSF1 pSer326 was related to poorer prognosis. These findings indicate that activation of HSF1 at Ser326 residue and transcription of HSP27 is related to the maintenance of gynecological CSCs/CICs.

RNA-Binding Proteins in Female Reproductive Pathologies.

RNA-binding proteins are key regulatory molecules involved primarily in post-transcriptional gene regulation of RNAs. Post-transcriptional gene regulation is critical for adequate cellular growth and survival. Recent reports have shown key interactions between these RNA-binding proteins and other regulatory elements, such as miRNAs and long noncoding RNAs, either enhancing or diminishing their response to RNA stabilization. Many RNA-binding proteins have been reported to play a functional role in mediation of cytokines involved in inflammation and immune dysfunction, and some have been classified as global post-transcriptional regulators of inflammation. The ubiquitous expression of RNA-binding proteins in a wide variety of cell types and their unique mechanisms of degradative action provide evidence that they are involved in reproductive tract pathologies. Aberrant inflammation and immune dysfunction are major contributors to the pathogenesis and disease pathophysiology of many reproductive pathologies, including ovarian and endometrial cancers in the female reproductive tract. Herein, we discuss various RNA-binding proteins and their unique contributions to female reproductive pathologies with a focus on those mediated by aberrant inflammation and immune dysfunction.

Genetic association between PAX2 and mullerian duct anomalies in Han Chinese females.

PURPOSE: The study aims to investigate the genetic association between paired box gene 2 (PAX2) and mullerian duct anomalies (MDA) in Chinese Han females. METHODS: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to identify the genotypes of three tag single nucleotide polymorphisms (SNPs) in PAX2 in 362 MDA cases and 406 controls. RESULTS: We found that one tag SNP (rs12266644) of PAX2 was associated with susceptibility to MDA. The genotype distributions of the SNP rs12266644 have a statistically significant difference in the MDA patients and controls with a p value = 0.008. In the dominant model, we also observed that the GT + TT genotype increased the risk for MDA (p = 0.015, OR = 1.637, 95 % CI = 1.096-2.443). CONCLUSION: The polymorphism rs12266644 of PAX2 might be a risk factor for MDA in Chinese Han females.

Expressions of NDRG1, VEGF and Ki-67 in Condyloma Acuminatum.

The objective of this study was to explore the expressions and significance of NDRG1 (N-myc downregulated gene family 1), VEGF (vascular endothelial growth factor) and Ki-67 in lesions of Condyloma Acuminatum (CA). Immunohistochemistry was adopted to measure the expressions of NDRG1, VEGF and Ki-67 in 48 cases of CA and 18 normal skin controls. The positive rates of NDRG1, VEGF and Ki-67 were 63. 83.33% (40/48), 93.75% (45/48) and 85.42% (41/48) in the CA tissues, and 27.78% (5/18), 94.44%(17/18) and 61.11% (11/18) in the controls, respectively. The intensities of the expressions of NDRG1, VEGF and Ki-67 in CA tissues were significantly higher than those in the controls. There were significant differences both in the positive rates and the expression intensities of NDRG1, VEGF and Ki-67 between the two groups (P less than0.05). The Spearman’s Rank-Order Correlation analysis indicated that the expressions of NDRG1 protein and VEGF protein were positively correlated by the Spearman’s Rank-Order Correlation analysis (r = 0.346, P=0.016). For the CA tissues with high expressions of NDRG1 and VEGF, NDRG1 and VEGF influenced both the occurrence and development of CA.

Host Nectin-1 Promotes Chlamydial Infection in the Female Mouse Genital Tract, but Is Not Required for Infection in a Novel Male Murine Rectal Infection Model.

Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen, but more than 70% of patients fail to seek treatment due to the asymptomatic nature of these infections. Women suffer from numerous complications from chronic chlamydial infections, which include pelvic inflammatory disease and infertility. We previously demonstrated in culture that host cell nectin-1 knockdown significantly reduced chlamydial titers and inclusion size. Here, we sought to determine whether nectin-1 was required for chlamydial development in vivo by intravaginally infecting nectin-1-/- mice with Chlamydia muridarum and monitoring chlamydial shedding by chlamydial titer assay. We observed a significant reduction in chlamydial shedding in female nectin-1-/- mice compared to nectin-1+/+ control mice, an observation that was confirmed by PCR. Immunohistochemical staining in mouse cervical tissue confirmed that there are fewer chlamydial inclusions in Chlamydia-infected nectin-1-/- mice. Notably, anorectal chlamydial infections are becoming a substantial health burden, though little is known regarding the pathogenesis of these infections. We therefore established a novel male murine model of rectal chlamydial infection, which we used to determine whether nectin-1 is required for anorectal chlamydial infection in male mice. In contrast to the data from vaginal infection, no difference in rectal chlamydial shedding was observed when male nectin-1+/+ and nectin-1-/- mice were compared. Through the use of these two models, we have demonstrated that nectin-1 promotes chlamydial infection in the female genital tract but does not appear to contribute to rectal infection in male mice. These models could be used to further characterize tissue and sex related differences in chlamydial infection.

Ultrasound diagnosis in gynecological acute abdomen.

As ultrasound diagnosis is applied more frequently in gynecological acute abdomen, we carried out this study to discuss the diagnosis of endometriosis with ultrasound imaging and analyze the efficacy of microRNA used for diagnosing endometriosis and evaluating prognosis by comparing differentially expressed microRNA in subjects with or without endometriosis. Ultrasound examination results and clinical pathological examination results of 60 cases of gynecological acute abdomen were compared. Blood samples were collected from patients with endometriosis. Of 60 cases, 38 cases recurred in 20 months after surgery and the remaining 22 cases had no recurrence in the 30-month follow-up. Additionally, blood was collected from 40 patients without endometriosis as control. Then total RNA was extracted from these blood samples to determine the difference of expression of microRNA (miR-17-5p, miR-20a, miR-199a and miR-141). Compared to healthy subjects, the endometriosis patients showed significantly increased expression of miR-199a, but the expression of miR-17-5p, miR-20a and miR-141 had an obvious decrease; the differences were statistically significant (p less than 0.01). For recurred cases, miR-199 showed a remarkably high expression and miR-17-5p and miR-20a expressed significantly low.

Aberrant HOXA10 Methylation in Patients With Common Gynecologic Disorders: Implications for Reproductive Outcomes.

HomeoboxA10 (HOXA10) is a transcription factor that is crucial for the development and patterning of the uterus during embryogenesis. In the adult endometrium, HOXA10 expression is regulated by steroid hormones and embryonic signals. Expression of sufficient HOXA10 messenger RNA is essential to endometrial receptivity and embryo implantation. Aberrant methylation is believed to alter the expression of HOXA10. Methylation of this gene may be associated with decreased fertility, implantation defects, and/or reproductive wastage seen in certain disease states that affect the female reproductive tract. This study describes the differences in methylation patterns of HOXA10 gene in uterine myomas, endometriosis, uterine septum, Asherman syndrome, or uterine polyps of women undergoing hysteroscopic surgery. In the endometrium of uteri with polyps, submucosal myomas, and intramural myomas, there were CpG sites within the HOXA10 gene that were highly methylated compared to controls. The HOXA10 gene in women with endometriosis was hypomethylated compared to controls. DNA methylation may be a common molecular mechanism that results in reproductive dysfunction seen in gynecologic disease.