Publications by authors named "Ningxia Sun"

15 Publications

  • Page 1 of 1

The Value of Circulating microRNAs for Diagnosis and Prediction of Preeclampsia: a Meta-analysis and Systematic Review.

Reprod Sci 2021 Nov 24. Epub 2021 Nov 24.

Department of Medical Genetic, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.

Preeclampsia (PE) is one of the main causes of maternal death worldwide, but our understanding of the molecular characteristics of disease progression is limited. In this meta-analysis, we aimed to assess the value of peripheral blood microRNAs (miRNAs) as diagnostic and predictive markers of PE. We screened PubMed, Web of Science, and Embase databases; searched articles about "miRNAs and PE" up to November 30, 2020; and conducted biological information and subgroup analysis. We used QUADAS-2 (quality assessment of diagnostic accuracy studies-2) to evaluate the included articles by two independent reviewers, calculated the combined diagnostic and predictive indicators using the random effects model, explored the sources of potential heterogeneity through subgroup analysis, and evaluated publication bias using Deeks' funnel plot asymmetry test using Stata 14.0 and Review Manager 5.3 software. Forty-three miRNAs from 15 studies, including 2042 healthy controls and 2685 PE patients, had a pooled sensitivity of 0.86 (95% CI: 0.81-0.90), specificity of 0.89 (95% CI: 0.85-0.92), and an AUC of 0.94 (95% CI: 0.91-0.96). Moreover, before 20 weeks of gestation, the combined sensitivity was 0.86 (95% CI: 0.75-0.92), and the specificity was 0.90 (95% CI: 0.83-0.95), which indicated that some of the circulating miRNAs had changed significantly before the clinical symptoms appeared in PE patients. Circulating miRNAs have high diagnostic and predictive accuracy and may be used as non-invasive biomarkers for the diagnosis and prediction of PE. However, a large sample prospective study is still needed.
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http://dx.doi.org/10.1007/s43032-021-00799-6DOI Listing
November 2021

Comprehensive Characterization of Microbial Community in the Female Genital Tract of Reproductive-Aged Women in China.

Front Cell Infect Microbiol 2021 16;11:649067. Epub 2021 Sep 16.

Center for Reproductive Medicine, Changzheng Hosptial, Second Military Medical University, Shanghai, China.

The microbiota in the human body play critical roles in many physiological and pathological processes. However, the diversity and dynamics of the female genital tract (FGT) microbiota have not been fully unveiled. In this study, we characterized the microbiome variations in reproductive-aged Chinese women, and we revealed that the cervicovaginal microbiota were dominated by . Overall, the composition of microbiota in the uterine cavity was more diverse than that in the vagina and cervix. A positive correlation between and was observed in both the vagina and the cervix, suggesting that these two species might have a symbiotic relationship in the cervicovaginal microbiota. Moreover, we, for the first time, stratified the reproductive-aged Chinese women into subgroups, based on their microbiome profiles. Furthermore, we identified the bacteria whose abundance changed in the uterine cavity of infertile patients when compared with healthy controls, such as and . Functionally, the metabolism-related pathways, neurotrophin signaling pathway, and adipocytokine signaling pathway were predominantly dysregulated in the uterine cavity of infertile patients. In conclusion, we characterized a comprehensive microbial landscape in FGT, as well as their functional roles in female infertility of the Chinese population.
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http://dx.doi.org/10.3389/fcimb.2021.649067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482844PMC
October 2021

Roles of noncoding RNAs in preeclampsia.

Reprod Biol Endocrinol 2021 Jul 2;19(1):100. Epub 2021 Jul 2.

Department of Medical Genetic, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.

Preeclampsia (PE) is an idiopathic disease that occurs during pregnancy. It comprises multiple organ and system damage, and can seriously threaten the safety of the mother and infant throughout the perinatal period. As the pathogenesis of PE is unclear, there are few specific remedies. Currently, the only way to eliminate the clinical symptoms is to terminate the pregnancy. Although noncoding RNA (ncRNA) was once thought to be the "junk" of gene transcription, it is now known to be widely involved in pathological and physiological processes, including pregnancy-related disorders. Moreover, there is growing evidence that the unbalanced expression of specific ncRNA is involved in the pathogenesis of PE. In the present review, we summarize the expression patterns of ncRNAs, i.e., microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), and the functional mechanisms by which they affect the development of PE, and examine the clinical significance of ncRNAs as biomarkers for the diagnosis of PE. We also discuss the contributions made by genetic polymorphisms and epigenetic ncRNA regulation to PE. In the present review, we wish to explore and reinforce the clinical value of ncRNAs as noninvasive biomarkers of PE.
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http://dx.doi.org/10.1186/s12958-021-00783-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252232PMC
July 2021

The Efficacy and Safety of the mTOR Signaling Pathway Activator, MHY1485, for Activation of Human Ovarian Tissue.

Front Genet 2020 4;11:603683. Epub 2021 Feb 4.

Shanghai Key Laboratory of Embryo Original Diseases, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Premature ovarian insufficiency (POI) is characterized by abnormal ovarian function before the age of 40. POI showed that primordial follicles developed in disorder. mTOR signaling plays a vital role in the process of follicle development. It has been verified that the mTOR signaling pathway activator, MHY1485, can promote primordial follicle development in mice. We considered that MHY1485 would be a promising fertility preservation method for POI patients.

Methods: The fragmented ovarian tissues of normal woman was cultured with activator MHY1485 , and then the control and activated ovaries were transplanted into the kidney capsules of ovariectomized mice. We then used the Infinium Human Methylation EPIC BeadChip to verify the DNA methylation level of ovarian tissues, thus exploring the effectiveness of them.

Results: MHY1485 stimulated mTOR, S6K1, and rpS6 phosphorylation. Cultured with MHY1485, ovarian weights increased and endocrine function was restored. The number of growing follicles was increased. The activation process did not induce histological changes or abnormal DNA methylation occurrence.

Conclusion: MHY1485 for activation (IVA) is effective for ovarian rejuvenation and is a potential therapeutic treatment for POI patients.
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http://dx.doi.org/10.3389/fgene.2020.603683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890121PMC
February 2021

H3K4me3-Mediated Upregulation of LncRNA-HEIPP in Preeclampsia Placenta Affects Invasion of Trophoblast Cells.

Front Genet 2020 11;11:559478. Epub 2020 Dec 11.

Department of Reproductive Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, China.

Preeclampsia (PE) is a pregnancy-related disease defined as onset of hypertension and proteinuria after the 20th week of pregnancy, which causes most maternal and perinatal morbidity and mortality. Although placental dysfunction is considered as the main cause of PE, the exact pathogenesis of PE is not yet fully understood. Long non-coding RNAs (lncRNAs) are implicated in a broad range of physiological and pathological processes, including the occurrence of PE. In this study, we investigated the expression and functions of HIF-1α pathway-related lncRNA-HEIPP (high expression in PE placenta) in the pathogenesis of PE. The expression of lncRNA-HEIPP in the placenta from women who underwent PE was screened by lncRNA microarray and then verified using real-time polymerase chain reaction. Then, the methylation profile of the promoter and the enrichment of H3K4me3 binding were assessed by bisulfite pyrosequencing and chromatin immunoprecipitation (ChIP)-quantitative polymerase chain reaction (qPCR) assay, respectively. It was found that the level of lncRNA-HEIPP in the PE placenta was significantly higher than that in normal placenta and was increased in HTR-8/SVneo human trophoblast cells upon hypoxia treatment. Moreover, we reported that H3K4me3 manifested significantly higher promoter occupancy on promoter in HTR-8/SVneo cells upon hypoxia treatment and found that the downregulation of lncRNA-HEIPP promoted trophoblast invasion. Our findings suggested that the hypoxia-induced expression of lncRNA-HEIPP mediated by H3K4me3 modification in trophoblast may contribute to the pathogenesis of PE.
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http://dx.doi.org/10.3389/fgene.2020.559478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793904PMC
December 2020

The psychosocial impact of premature ovarian insufficiency on male partners and their perceptions of the disease.

Psychol Health Med 2021 Dec 26;26(10):1248-1257. Epub 2020 Aug 26.

Center for Reproductive Medicine, Changzheng Hosptial, Second Military Medical University, Shanghai, China.

Premature ovarian insufficiency (POI) is affecting about 1% women of reproductive age. However, current studies have primarily focused on women with the views of male partners greatly absent from the literature. We conduct this research to investigate the psychosocial effect of POI on male partners and their perceptions of the disease.52 male partners of POI patient (experiment group) and 52 controls (control group) were available for analysis. Anxiety, depression, and marital relationship were assessed for male partners in both groups. A questionnaire about perceptions of POI was completed by the experiment group. Male partners of POI patient experienced greater levels of anxiety (10.96 versus 4.88; < 0.01) and depression (12.23 versus 5.19; < 0.01) compared with controls. In addition, they experienced worse marital relationship in several aspects than their counterparts. The findings also demonstrate that most POI patient male partners had inadequate and inaccurate knowledge about their partners' disease, which may be the results of insufficient professional counseling from health-care practitioners. Moreover, their understanding level of the disease was correlated to anxiety ( = -0.64; < 0.01), depression ( = -0.38; < 0.01), and communication ( = 0.28; < 0.05).The study highlights the need for health-care services, as well as support and professional information resources aimed at POI patients' male partners.
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http://dx.doi.org/10.1080/13548506.2020.1810717DOI Listing
December 2021

Novel ZP1 pathogenic variants identified in an infertile patient and a successful live birth following ICSI treatment.

Clin Genet 2020 05 7;97(5):787-788. Epub 2020 Jan 7.

Center for Reproductive Medicine, Changzheng Hosptial, Second Military Medical University, Shanghai, China.

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http://dx.doi.org/10.1111/cge.13693DOI Listing
May 2020

Aberrant expression of imprinted lncRNA MEG8 causes trophoblast dysfunction and abortion.

J Cell Biochem 2019 10 2;120(10):17378-17390. Epub 2019 Jul 2.

Changzheng Hospital, Reproductive Medicine Center, Shanghai, China.

Long noncoding RNAs (lncRNAs) are a group of noncoding RNAs whose nucleotides are longer than 200 bp. Previous studies have shown that they play an important regulatory role in many developmental processes and biological pathways. However, the contributions of lncRNAs to placental development are largely unknown. Here, our study aimed to investigate the lncRNA expression signatures in placental development by performing a microarray lncRNA screen. Placental samples were obtained from pregnant C57BL/6 female mice at three key developmental time points (embryonic day E7.5, E13.5, and E19.5). Microarrays were used to analyze the differential expression of lncRNAs during placental development. In addition to the genomic imprinting region and the dynamic DNA methylation status during placental development, we screened imprinted lncRNAs whose expression was controlled by DNA methylation during placental development. We found that the imprinted lncRNA Rian may play an important role during placental development. Its homologous sequence lncRNA MEG8 (RIAN) was abnormally highly expressed in human spontaneous abortion villi. Upregulation of MEG8 expression in trophoblast cell lines decreased cell proliferation and invasion, whereas downregulation of MEG8 expression had the opposite effect. Furthermore, DNA methylation results showed that the methylation of the MEG8 promoter region was increased in spontaneous abortion villi. There was dynamic spatiotemporal expression of imprinted lncRNAs during placental development. The imprinted lncRNA MEG8 is involved in the regulation of early trophoblast cell function. Promoter methylation abnormalities can cause trophoblastic cell defects, which may be one of the factors that occurs in early unexplained spontaneous abortion.
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http://dx.doi.org/10.1002/jcb.29002DOI Listing
October 2019

Caveolin-1 promotes trophoblast cell invasion through the focal adhesion kinase (FAK) signalling pathway during early human placental development.

Reprod Fertil Dev 2019 May;31(6):1057-1067

Centre of Reproductive Medicine, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China; and Corresponding authors. Emails:

Normal implantation and placental development depend on the appropriate differentiation and invasion of trophoblast cells. Inadequate trophoblast cell invasion results in pregnancy-related disorders, which endanger both mother and fetus; however, the mechanism of early placental development has not been fully explained. In this study we conducted gene expression profile analysis using mouse placental tissues at different developmental stages (embryonic day (E)7.5, E14.5 and E19.5) using series tests of cluster (STC) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses. Focal adhesion kinase (FAK) signalling pathway-related gene expression levels were verified using quantitative reverse transcription polymerase chain reaction and western blot. The results showed that caveolin-1 (Cav1) was downregulated in the placenta of unexplained spontaneous abortion subjects compared with that of induced abortion. Furthermore, by modulating CAV1 expression levels, CAV1 was shown to promote human trophoblast cell proliferation, migration and invasion by activating the FAK signalling pathway. These results indicate that CAV1 and the FAK signalling pathway are crucial for early placental development, which sheds new light on our understanding of the mechanisms of human trophoblast cell invasion and early development of the placenta.
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http://dx.doi.org/10.1071/RD18296DOI Listing
May 2019

Outcomes of poor responders following growth hormone co-treatment with IVF/ICSI mild stimulation protocol: a retrospective cohort study.

Arch Gynecol Obstet 2018 May 2;297(5):1317-1321. Epub 2018 Mar 2.

Reproductive Medicine Center, Second Military Medical University, Changzheng Hospital, 415 Fengyang Road, Shanghai, 200003, China.

Purpose: No research has studied the effect of GH co-treatment in mild stimulation protocol for poor responders. We therefore conducted this retrospective analysis to assess the outcome of IVF/ICSI cycles after the adjunct GH use to the mild stimulation protocol in poor responders.

Methods: 132 poor responders who received mild stimulation protocol at Reproductive Medicine Center of Changzheng Hospital from January 2014 to December 2016 were included in this study. Good-quality embryo rate, clinical pregnancy rate, and live birth rate were compared between the GH group (n = 61) and control group (n = 71).

Results: IVF good-quality embryo rate (68.1 versus 51.5%; P = 0.008*) and ICSI good-quality embryo rate (53.9 versus 36.7%; P = 0.045*) was significantly higher in the GH group. Though the clinical outcomes did not reach a statistically significant difference between the two groups due to the limited sample size, there was a trend of higher rate in GH group in the aspect of clinical pregnancy rate (52.4 versus 47.1%; P = 0.609) and live birth rate (35.7 versus 27.5%; P = 0.392).

Conclusion: The results suggested that the adjuvant GH treatment in mild stimulation protocol for poor responders could significantly improve good-quality embryo rate, and might therefore improve the clinical outcomes.
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http://dx.doi.org/10.1007/s00404-018-4725-5DOI Listing
May 2018

Conservative laparoscopic management of adnexal torsion based on a 17-year follow-up experience.

J Int Med Res 2018 Apr 27;46(4):1685-1689. Epub 2018 Feb 27.

Reproductive Medicine Center, Changzheng Hospital, Second Military Medical University, Shanghai, China.

Laparoscopic unwinding of adnexal torsion has been proposed for decades. However, this technique is still controversial regarding the concern of thromboembolic events. We present two cases of conservative laparoscopic management of adnexal torsion. In the first case, a 16-year-old adolescent with serous cystadenoma was successfully managed by untwisting and cystectomy. We followed up this patient for 17 years with regular re-examinations in our hospital. To the best of our knowledge, this is the longest follow-up reported of this condition. In the second case, a 32-year-old infertile woman who received oocyte retrieval 3 days before being admitted to hospital was referred to hospital with right ovarian torsion. We treated her successfully based on our long-term follow-up experience, and she is now asymptomatic and in her 7th month of pregnancy.
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http://dx.doi.org/10.1177/0300060517754025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091833PMC
April 2018

A systematic review and meta-analysis of nonpharmacological adjuvant interventions for patients undergoing assisted reproductive technology treatment.

Int J Gynaecol Obstet 2017 Dec 25;139(3):268-277. Epub 2017 Sep 25.

Reproductive Medicine Center, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.

Background: Assisted reproductive technology (ART) is not always successful, yet places a high psychological burden on individuals.

Objectives: To assess whether nonpharmacological adjuvant interventions could improve outcomes among patients receiving ART.

Search Strategy: Electronic databases were searched from inception to March 2017, using keywords such as "fertility treatment," "emotional distress," and "clinical pregnancy."

Selection Criteria: Reports of randomized controlled trials investigating the impact of nonpharmacological interventions on emotional disorders and the pregnancy rate in patients receiving ART published in any language were included.

Data Collection And Analysis: Data were extracted into a predesigned form. Psychological ratings were pooled using standardized mean differences (SMDs). Heterogeneity was assessed. The primary outcome measures were psychological ratings at baseline and after intervention.

Main Results: Overall, 34 randomized controlled trials, with a total of 7213 patients, met the inclusion criteria. Nonpharmacological interventions reduced anxiety when compared with control interventions (SMD 0.25, 95% confidence interval 0.08-0.42; I =85%), but they had no significant effects on depression and infertility distress.

Conclusions: Nonpharmacological interventions could improve the psychological outcomes of patients undergoing ART treatment.
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http://dx.doi.org/10.1002/ijgo.12310DOI Listing
December 2017

The mutation-free embryo for in vitro fertilization selected by MALBAC-PGD resulted in a healthy live birth from a family carrying PKD 1 mutation.

J Assist Reprod Genet 2017 Dec 19;34(12):1653-1658. Epub 2017 Aug 19.

Division of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, People's Republic of China.

Background: Autosomal dominant polycystic kidney disease (ADPKD, autosomal dominant PKD or adult-onset PKD) is the most prevalent and potentially lethal kidney disease that is hereditary and lacks effective treatment. Preimplantation genetic diagnosis (PGD) of embryos in assistant reproductive technology (ART) helps to select mutation-free embryos for blocking ADPKD inheritance from the parents to their offspring. However, there are multiple pseudogenes in the PKD1 coding region, which make blocking ADPKD inheritance by PGD complicated and difficult. Therefore, this technique has not been recommended and used routinely to ADPKD family plan.

Methods And Results: Here, we report a new strategy of performing PGD in screening (target-) mutation-free embryos. We firstly used a long-range PCR amplification and next generation sequencing to identify the potential PKD1 mutant(s). After pathogenic variants were detected, multiple annealing and looping-based amplification cycles (MALBAC), a recently developed whole genome amplification method, was used to screen embryo cells. We successfully distinguished the mutated allele among pseudogenes and obtained mutation-free embryos for implantation. The first embryo transfer attempt resulted in a healthy live birth free of ADPKD condition and chromosomal anomalies which was confirmed by aminocentesis at week 18 of gestation, and by performing live birth genetic screening.

Conclusions: The first MALBAC-PGD attempt in ADPKD patient resulted in a healthy live birth free of ADPKD and chromosomal anomalies. MALBAC-PGD also enables selecting embryos without aneuploidy together and target gene mutation, thereby increasing implantation and live birth rates.
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http://dx.doi.org/10.1007/s10815-017-1018-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714816PMC
December 2017

Molecular regulation of ovarian cancer cell invasion.

Tumour Biol 2014 Nov 15;35(11):11359-66. Epub 2014 Aug 15.

Department of Obstetrics and Gynecology, Shanghai Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.

The molecular mechanism underlying ovarian cancer invasiveness and metastasis remains unclear. Since significant downregulation in microRNA 200 (miRNA200) family (miR200a, miR200b, and miR200c) has been reported in the invasive ovarian cancer cells, here, we used two human ovarian cancer cell lines, OVCAR3 and SKOV3, to study the molecular basis of miR200, matrix metalloproteinase 3 (MMP3) activation, and cancer invasiveness. We found that overexpression of either miR200 family member in OVCAR3 or SKOV3 cells significantly inhibited production and secretion of MMP3 and cancer invasiveness. Moreover, forced MMP3 expression abolished miR200-induced inhibition of ovarian cancer cell invasiveness, suggesting that miR200 family inhibited ovarian cell invasiveness via downregulating MMP3. Furthermore, ZEB1, a major target of miR200, was inhibited by miR200 overexpression. Forced ZEB1 expression abolished miR200-induced inhibition of ovarian cancer cell invasiveness, suggesting that ZEB1 is a direct target of miR200 for inhibiting ovarian cell invasiveness. Finally, phosphorylated SMAD3 (pSMAD3), a major partner of ZEB1, was efficiently inhibited by miR200, which could be restored by forced expression of ZEB1, but not by forced expression of MMP3, suggesting that ZEB1/pSMAD3 is signaling cascade upstream of MMP3 in this model. Taken together, our data suggest that miR200 family inhibited ovarian cancer cell invasiveness and metastasis by downregulating MMP3, possibly through ZEB1/pSMAD3.
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http://dx.doi.org/10.1007/s13277-014-2434-7DOI Listing
November 2014

A case of extramedullary solitary plasmacytoma arising at the uterine cervix.

Eur J Gynaecol Oncol 2012 ;33(4):423-4

Department of Obstetrics and Gynecology, Shanghai Changzheng Hospital, China.

Extramedullary plasmacytomas are localized plasma cell neoplasms that arise in tissues other than bone and bone marrow. Primary plasmacytomas of the female genital tract are extremely rare and present a substantial diagnostic challenge. We report a case of a 38-year-old woman who presented with an endocervical polypoid. Surgical removal of the polyp was carried out. The final pathological report revealed primary plasmacytoma of the uterine cervix. The diagnosis was further facilitated by the use of immunohistochemistry and clonal immunoglobulin heavy-chain gene rearrangement. We performed a simple hysterectomy by laparoscopy on the patient and kept a close follow-up. She has remained well for more than eight years. The clinical characteristics and histopathologic findings of plasmacytoma of the uterine cervix are discussed.
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November 2012
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