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Introduction:Because early diagnosis and timely detection of preeclampsia (PE) remains challenge. This study aims to explore the differential expression and pathogenic mechanism of the lncRNA MIR210HG in peripheral blood, which will lay the basis for its use as a biomarker of PE. Methods: Total RNA was extracted from the peripheral blood of 88 women with preeclamptic pregnancies and 81 women with normal pregnancies. The MIR210HG expression levels were determined by RT-PCR and western blot. SiRNA and MIR210HG overexpression plasmids were constructed and transfected into human trophoblast and vascular endothelial cells. Results: The lncRNA MIR210HG was significantly upregulated in the peripheral blood of patients with PE compared to the control group. Additionally, the expression level of MIR210HG in patients with early-onset PE was significantly higher than that of the control and late-onset PE groups. CDHR5, identified by bioinformatics predictions after RT-PCR confirmation, was upregulated in placental tissue compared to the control group. Furthermore, cytology experiments confirmed that knockdown of MIR210HG also decreased CDHR5 in human trophoblast and vascular endothelial cells. After knockdown of CDHR5, expression of MIR210HG was also reduced. Discussion: The lncRNA MIR210HG is highly expressed in the peripheral blood of PE, indicating MIR210HG may become a potential biomarker for the diagnosis and prediction of PE. In addition, MIR210HG may interact with CDHR5 to jointly promote the progression of PE. However, further experiments are needed to confirm the pathogenic mechanism.

Background Accumulating evidence indicates that infertile individuals are often associated with poor mental health. However, there are few studies focus on the trauma exposure of infertile individuals. Meanwhile, adverse childhood experiences (ACE) are often associated with poor mental health, especially the development of post-traumatic stress symptoms (PTSS). Therefore, the present study aimed to investigate the condition of traumatic exposure and the prevalence of PTSS in people with infertile in Shanghai, and then explore the effect of ACE among infertile people of childbearing age who reported experiencing trauma exposure. Methods The cross-sectional study was conducted from October 2021 to September 2022. A total of 213 infertile patients in Shanghai Changzheng Hospital were selected by random sampling. After screening, a total of 194 experimental data were obtained. The participants filled out the demographic questionnaires, self-developed trauma exposure questionnaire. Childhood trauma questionnaire (CTQ) and the primary care PTSD screen for DSM-5 (PC-PTSD-5) were used to investigate ACE and PTSS, respectively. Results Traumatic events were experienced in 41.8% of infertility patients. Only 4.10% of infertile patients had PTSS. Maternal education level (p = 0.019) had significant influence on whether PTSS occurred in patients. Logistic regression analysis indicated age, emotional abuse (EA) and physical neglect (PN) increased the probability of patients reporting trauma exposure, while emotional neglect (EN) reduced the possibility of reporting trauma. Conclusions Undesirable the high incidence of traumatic experience of infertility population, especially ACE, has an important impact on their treatment and recovery at the moment, as well as the future development of mental health. More evidence between PTSS and trauma exposure are needed in the future to strengthen this conclusion.

This study attended to systematically analyze the patients’ fertility and clinical outcomes of ART who suffered with ADPKD. Methods: 61 couples who underwent PGT-M at our Centre from January 2015 to July 2021 were selected for retrospective analysis. Patients were divided into Group Aand B. Results: Our data showed the high-quality embryo rate of Group A was higher than that of Group B (70.1% vs.51.3%, PP > 0.05). The analysis of fertility-related data showed that there was no significant correlation by further comparing the ADPKD gene mutation sites, and no significant difference in the euploidy rate of embryos between Group A and B (66.7% vs. 72.6%, P > 0.05). Conclusion: The ADPKD gene was not significantly associated with patients' good-quality embryo rates. Although male patients who suffered from ADPKD showed a higher proportion of teratospermia and severe oligoasthenospermia,which resulted in a lower good embryo quality rate, the euploidy rate of embryos or clinical outcome of ART was not significantly affected.

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.

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.

Granulosa cells (GCs) play a critical role in driving the formation of ovarian follicles and building the cumulus-oocyte complex surrounding the ovum. We are particularly interested in assessing oocyte quality by examining the detailed gene expression profiles of human cumulus single cells. Using single-cell RNAseq techniques, we extensively investigated the single-cell transcriptomes of the cumulus GC populations from two women with normal ovarian function. This allowed us to elucidate the endogenous heterogeneity of GCs by uncovering the hidden GC subpopulation. The subsequent validation results suggest that CD24(+) GCs are essential for triggering ovulation. Treatment with human chorionic gonadotropin (hCG) significantly increases the expression of CD24 in GCs. CD24 in cultured human GCs is associated with hCG-induced upregulation of prostaglandin synthase (ARK1C1, PTGS2, PTGES, and PLA2G4A) and prostaglandin transporter (SLCO2A1 and ABCC4) expression, through supporting the EGFR-ERK1/2 pathway. In addition, it was observed that the fraction of CD24(+) cumulus GCs decreases in PCOS patients compared to that of controls. Altogether, the results support the finding that CD24 is an important mediator of ovulation and that it may also be used for therapeutic target of ovulatory disorders.

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.

BackgroundPremature 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.MethodsThe fragmented ovarian tissues of normal woman was cultured with activator MHY1485 in vitro, 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.ResultsMHY1485 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 in vitro activation process did not induce histological changes or abnormal DNA methylation occurrence.ConclusionMHY1485 for in vitro activation (IVA) is effective for ovarian rejuvenation and is a potential therapeutic treatment for POI patients.

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 Lactobacillus. Overall, the composition of microbiota in the uterine cavity was more diverse than that in the vagina and cervix. A positive correlation between Lactobacillus iners and Lactobacillus crispatus 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 L. iners and L. crispatus. 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.

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

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. 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. 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.

Gender dysphoria (GD) is characterized by an incongruence between the gender assigned at birth and the gender with which one identifies. The biological mechanisms of GD are unclear. While common genetic variants are associated with GD, positive findings have not always been replicated. To explore the role of rare variants in GD susceptibility within the Han Chinese population, whole-genome sequencing of 9 Han female-to-male transsexuals (FtMs) and whole-exome sequencing of 4 Han male-to-female transsexuals (MtFs) were analyzed using a pathway burden analysis in which variants are first collapsed at the gene level and then by Gene Ontology terms. Novel nonsynonymous variants in ion transport genes were significantly enriched in FtMs (P- value, 2.41E-10; Fold enrichment, 2.8) and MtFs (P- value, 1.04E-04; Fold enrichment, 2.3). Gene burden analysis comparing 13 GD cases and 100 controls implicated RYR3, with three heterozygous damaging mutations in unrelated FtMs and zero in controls (P = 0.001). Importantly, protein structure modeling of the RYR3 mutations indicated that the R1518H mutation made a large structural change in the RYR3 protein. Overall, our results provide information about the genetic basis of GD.

In our study, transcriptome microarrays are used to identify differentially expressed miRNAs and mRNAs in cervical cancer specimens. We find that microRNA-145 (miR-145) expression is significantly decreased in cervical cancer tissues and cell lines, and is associated with advanced cancer stages, large tumor size and moderate/poor differentiation. We show that miR-145 targets the DNA damage repair-associated gene Helicase-like transcription factor (HLTF), which is involved in radio-resistance. Moreover, miR-145 over-expression in cervical cancer cells enhances radiosensitivity in vitro and in vivo. These results indicate that targeting miR-145 may be a novel radiosensitizing strategy for cervical cancer.

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. 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). 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). 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.

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; I2=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. This article is protected by copyright. All rights reserved.

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.

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.

Aggressive angiomyxoma is a rare soft-tissue tumour, typically occurring in the female pelvis and carrying a high risk of local infiltration and relapse. Surgery remains the first line of treatment, however some adjuvant treatments, such as gonadotrophin-releasing hormone (GnRH) agonists, have been used for primary treatment and for treatment against tumour recurrence. We describe a case of vulvar aggressive angiomyxoma in a 31-year old woman who underwent surgical excision of the tumour. Diagnosis was made on the basis of histopathological examination and positive immunohistochemical staining with oestrogen and progesterone receptors. Postsurgery, a GnRH agonist (3.75 mg triptorelin) was injected intramuscularly every month for 3 months to prevent tumour recurrence and, to date, no relapse has been observed. Whether treatment is with surgery, hormone therapy or both, it is clear that aggressive angiomyxoma requires close, long-term follow-up to monitor for disease recurrence and that the individualization of each case is essential for adequate management.