Effects of Particulate Matter on the Risk of Gestational Hypertensive Disorders and Their Progression.

Associations between particulate matter (PM) and gestational hypertensive disorders (GHDs) are well documented, but there is no evidence on the associations between PM and GHD progression, especially among those with assisted reproductive technology (ART) conceptions. To explore the effects of PM on the risk of GHDs and their progression among pregnant women with natural or ART conception, we enrolled 185,140 pregnant women during 2014-2020 in Shanghai and estimated the associations during different periods using multivariate logistic regression. During the 3 months of preconception, 10 µg/m3 increases in PM concentrations were associated with increased risks of gestational hypertension (GH) (PM2.5: aOR = 1.076, 95% CI: 1.034-1.120; PM10: aOR = 1.042, 95% CI: 1.006-1.079) and preeclampsia (PM2.5: aOR = 1.064, 95% CI: 1.008-1.122; PM10: aOR = 1.048, 95% CI: 1.006-1.092 ) among women with natural conception. Furthermore, for women with ART conceptions who suffered current GHD, 10 µg/m3 increases in PM concentrations in the third trimester elevated the risk of progression (PM2.5: aOR = 1.156, 95% CI: 1.022-1.306 ; PM10: aOR = 1.134, 95% CI: 1.013-1.270). In summary, women with natural conception should avoid preconceptional PM exposure to protect themselves from GH and preeclampsia. For women with ART conceptions suffering from GHD, it is necessary to avoid PM exposure in late pregnancy to prevent the disease from progressing.

Mutational screening of AGRN, SLC39A5, SCO2, P4HA2, BSG, ZNF644, and CPSF1 in a Chinese cohort of 103 patients with nonsyndromic high myopia.

Purpose: High myopia (HM) is one of the leading causes of irreversible vision loss in the world. Many myopia loci have been uncovered with linkage analysis, genome-wide association studies, and sequencing analysis. Numerous pathogenic genes within these loci have been detected in a portion of HM cases. In the present study, we aimed to investigate the genetic basis of 103 patients with nonsyndromic HM, focusing on the reported causal genes. Methods: A total of 103 affected individuals with nonsyndromic HM were recruited, including 101 patients with unrelated sporadic HM and a mother and son pair. All participants underwent comprehensive ophthalmic examinations, and genomic DNA samples were extracted from the peripheral blood. Whole exome sequencing was performed on the mother and son pair as well as on the unaffected father. Sanger sequencing was used to identify mutations in the remaining 101 patients. Bioinformatics analysis was subsequently applied to verify the mutations. Results: An extremely rare mutation in AGRN (c.2627A>T, p.K876M) was identified in the mother and son pair but not in the unaffected father. Another two mutations in AGRN (c.4787C>T, p.P1596L/c.5056G>A, p.G1686S) were identified in two unrelated patients. A total of eight heterozygous variants potentially affecting the protein function were detected in eight of the remaining 99 patients, including c.1350delC, p.V451Cfs*76 and c.1023_1024insA, p.P342Tfs*41 in SLC39A5; c.244_246delAAG, p.K82del in SCO2; c.545A>G, p.Y182C in P4HA2; c.415C>T, p.P139S in BSG; c.3266A>G, p.Y1089C in ZNF644; and c.2252C>T, p.S751L and c.1708C>T, p.R570C in CPSF1. Multiple bioinformatics analyses were conducted, and a comparison to a group with geographically matched controls was performed, which supported the potential pathogenicity of these variants. Conclusions: We provide further evidence for the potential role of AGRN in HM inheritance and enlarged the current genetic spectrum of nonsyndromic HM by comprehensively screening the reported causal genes.

The Expression of Markers Related to Ovarian Germline Stem Cells in the Mouse Ovarian Surface Epithelium and the Correlation with Notch Signaling Pathway.

BACKGROUND/AIMS: Ovarian germline stem cells (OGSCs) have been shown to mainly exist in the ovarian surface epithelium (OSE), but the activity changes of germline stem cells during different reproductive stages and the potential regulatory signaling pathway are still unknown. The Notch signaling pathway plays a key role in cell development, primordial follicles and stem cell proliferation. However, whether it plays a role in the proliferation of OGSCs is unknown. Here, we analyzed the activity changes of germline stem cells and the correlation between germline stem cells and the Notch signaling pathway. METHODS: The expression of germline stem cell markers Mvh, Ooc4 and the Notch molecules Notch1, Hes1, and Hes5 were detected during 3 days (3d), and 2, 12, 20 months (2m, 12m, 20m) mouse ovarian surface epithelium samples. DAPT, a specific inhibitor of the Notch pathway, was used to observe the influence of Notch signaling in the germline stem cells. RESULTS: The results showed that the levels of MVH and OCT4 decreased substantially with reproductive age in ovarian surface epithelium, and the same tendency was detected in the Notch signaling molecules Notch1, Hes1 and Hes5. Dual-IF results showed that the germline stem cell markers were co-expressed with Notch molecules in the ovarian surface epithelium. While, the expression of MVH and OCT4 were reduced when the ovaries were treated with DAPT and the levels were attenuated with increasing dose of DAPT. CONCLUSION: Taken together, our results indicate that the viability of OGSCs decreased with the age of the mouse ovaries, and the activity of OGSCs in the ovarian surface epithelium may be related to the Notch signaling pathway.

Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice.

BACKGROUND: The Hippo signaling pathway plays fundamental roles in stem cell maintenance in a variety of tissues and has thus implications for stem cell biology. Key components of this recently discovered pathway have been shown to be associated with primordial follicle activation. However, whether the Hippo signaling pathway plays a role in the development of Ovarian Germline Stem Cells (OGSCs) during physiological and pathological ovarian aging in mice is unknown. METHODS: Mice at the age of 7 days (7D), or of 2, 10, or 20 months (2M, 10M, 20M) and mice at 2M treated with TPT and CY/BUS drugs were selected as physiological and pathological ovarian aging models, respectively. Immunohistochemistry was used to assess the development of follicles, and the co-localization of genes characteristic of OGSCs with MST1, LATS2 and YAP1 was assessed by immunofluorescence, western blotting and real-time PCR methods. RESULTS: The Hippo signal pathway and MVH/OCT4 genes were co-expressed in the mouse ovarian cortex. The level and co-localization of LATS2, MST1, MVH, and OCT4 were significantly decreased with increased age, but YAP1 was more prevalent in the mouse ovarian cortex of 2M mice than 7D mice and was not observed in 20M mice. Furthermore, YAP1, MVH, and OCT4 were gradually decreased after TPT and CY/BUS treatment, and LATS2 mRNA and protein up-regulation persisted in TPT- and CY/BUS-treated mice. However, the expression of MST1 was lower in the TPT and CY/BUS groups compared with the control group. In addition, pYAP1 protein showed the highest expression in the ovarian cortexes of 7D mice compared with 20M mice, and the value of pYAP1/YAP1 decreased from 7D to 20M. Moreover, pYAP1 decreased in the TPT- and CY/BUS-treated groups, but the value of pYAP1/YAP1 increased in these groups. CONCLUSION: Taken together, our results show that the Hippo signaling pathway is associated with the changes that take place in OGSCs during physiological and pathological ovarian aging in mice. Thus, the Hippo signaling pathway may be involved in the development schedule of OGSCs.

Factors associated with the persistence of human papillomavirus after surgery in patients with cervical cancer.

OBJECTIVE: To determine the rate of human papillomavirus (HPV) persistence after surgery in patients with cervical cancer, and to analyze the factors associated with HPV persistence and viral load after surgery. METHODS: Medical records of women who underwent surgery for treatment of cervical cancer between 1 January 2018 and 30 June 2019 at Obstetrics and Gynecology Hospital of Fudan University in Shanghai, China, were retrospectively analyzed. Patients with persistent HPV infection after 2 years of follow-up were identified. Univariate and multivariate analyses were employed to determine the impact of various factors including patient age, menopausal status, parity, and surgical margin status on HPV persistence. The Wilcoxon test was used to analyze the factors that influenced postoperative HPV viral load. RESULTS: Altogether, 607 women were eligible for the final analysis. The persistence rates of HPV at 6 months, 1 year, and 2 years after surgery were 17.3, 13.7, and 10.2 %, respectively. In univariate analysis, the factors that were predictive of the persistence of HPV infection were old age, postmenopausal status, and positive vaginal incision margin with cancer. In multivariate analysis, the significant independent predictive factors were postmenopausal status and positive vaginal incision margin with cancer (P < 0.05, odds ratio (OR) = 2.289, 95 % confidence interval (CI): 1.262-4.150 and OR = 3.271, 95 % CI: 1.253-8.537, respectively). A vaginal lesion with cancer or squamous intraepithelial lesion (SIL) and positive vaginal incision margin influenced HPV viral load at 6 months after surgery (P < 0.05). CONCLUSIONS: Postmenopausal patients and those with positive vaginal incision margin with cancer are at an increased risk of HPV persistence after surgical treatment for cervical cancer. Vaginal lesions with cancer or SILs and positive vaginal incision margin are risk factors for high HPV viral load after surgery.

Delivery and neonatal outcomes of pregnant women during the Shanghai lockdown: A retrospective analysis.

Objectives: Shanghai witnessed an unprecedented outbreak of COVID-19 and experienced a strict lockdown from March 28, 2022 to May 31, 2022. Most studies to date are on the first lockdown after the outbreak in December 2019. This study aimed to examine the impact of lockdown on delivery and neonatal outcomes among uninfected pregnant women in the new phase of the COVID-19 outbreak. Methods: A retrospective analysis was conducted in the Obstetrics and Gynecology Hospital of Fudan University. Pregnant women without COVID-19 who delivered from March 28, 2022 to May 31, 2022 (lockdown group) and the same period in 2021 (non-lockdown group) were recruited for this study. Logistic regression models and 1 : 1 propensity score matching (PSM) were used to assess the effect of lockdown on delivery outcomes. Results: A total of 2,962 patients were included in this study, 1,339 of whom were from the lockdown group. Compared with the non-lockdown group, pregnant women giving birth during lockdown had an increased risk of term prelabor rupture of membranes (TPROM) (aOR = 1.253, 95% CI: 1.026-1.530), and decreased risks of postpartum hemorrhage (PPH) (aOR = 0.362, 95% CI: 0.216-0.606) and fetal malformation (aOR = 0.309, 95% CI: 0.164-0.582). The risk of large for gestational age (LGA) (aOR = 0.802, 95% CI: 0.648-0.992) and rate of admission to the neonatal intensive care unit (NICU) (aOR = 0.722, 95% CI: 0.589-0.885) also significantly declined. After 1 : 1 PSM, the impact of lockdown on the risk of TPROM (aOR = 1.501, 95% CI: 1.083-2.080), PPH (aOR = 0.371, 95% CI: 0.211-0.654), fetal malformation (aOR = 0.332, 95% CI: 0.161-0.684), LGA (aOR = 0.749, 95% CI: 0.594-0.945) and rate of admission to the NICU (aOR = 0.700, 95% CI: 0.564-0.869) all remained. There were no other delivery or neonatal outcomes affected by the lockdown after the COVID-19 outbreak. Conclusion: This study indicated a significant increase in the risk of term PROM, significant decreases in the risk of PPH, fetal malformation and LGA, and a marked decline in the rate of admission to the NICU during Shanghai Lockdown.

Associations between short-term and long-term exposure to particulate matter and preterm birth.

Despite the longstanding evidence on the effect of air pollutants on preterm birth (PTB), few studies have focused on its subtypes, including spontaneous preterm birth (sPTB) and medically indicated preterm birth (miPTB). Most studies evaluated only the short-term or long-term effects of particulate matter (PM) on PTB. Thus, we designed this study, based on a cohort of 179,385 women, to evaluate both short- and long-term effects of PM with diameters ≤2.5 µm and ≤10 µm (PM2.5 and PM10) on PTB, sPTB and miPTB in Shanghai. Generalized additive models (GAMs) were applied to evaluate short-term effects. Lagged effects were identified using different lag structures. Exposure-response correlation curves were plotted using GAMs after adjustment for confounders. ORs and 95% CIs were calculated using logistic regression to estimate the long-term effect after adjustment for confounders. There was 5.67%, 3.70% and 1.98% daily incidence of PTB, sPTB, and miPTB on average. Every 10 µg/m3 increase in PM2.5 and PM10 was positively associated with PTB and sPTB at lag 2 day. The exposure-response curves (lag 2 day) indicated a rapid increase in sPTB for PM2.5 and a linear increase for PM10, in PTB for PM2.5 and PM10 at concentrations over 100 µg/m3. Regarding long-term exposure, positive associations were found between 10 µg/m3 increases in PM2.5 and PM10 in 3rd trimester and greater odds of sPTB (aOR: 1.042, 95% CI: 1.018-1.065, and 1.018, 95% CI:1.002-1.034), and during the 3 months before conception and miPTB (aOR: 1.023, 95% CI: 1.003-1.042, and 1.017, 95% CI: 1.000-1.036). Acute exposure to PM2.5 and PM10 at lag 2 day and chronic exposure in 3rd trimester was significantly associated with sPTB, while miPTB was related to chronic exposure during the 3 months before pregnancy. These findings indicate that susceptibility windows of PM exposure can be influenced by different underlying etiologies of PTB.

Life Modifications and PCOS: Old Story But New Tales.

Polycystic ovary syndrome (PCOS) is defined as a kind of endocrine and metabolic disorder that affects female individuals of reproductive age. Lifestyle modifications, including diet modifications, exercise, and behavioral modification, appear to alleviate the metabolic dysfunction and improve the reproductive disorders of PCOS patients (particularly in obese women). Therefore, lifestyle modifications have been gradually acknowledged as the first-line management for PCOS, especially in obese patients with PCOS. However, the mechanism of lifestyle modifications in PCOS, the appropriate composition of diet modifications, and the applicable type of exercise modifications for specific female populations are rarely reported. We conducted a systematic review and enrolled 10 randomized controlled trials for inclusion in a certain selection. In this review, we summarized the existing research on lifestyle modifications in PCOS. We aimed to illustrate the relationship between lifestyle modifications and PCOS (referring to hyperandrogenism, insulin resistance as well as obesity) and also considered the priorities for future research. These results might be an invaluable tool to serve as a guide in lifestyle modifications as the intervention for PCOS and other related endocrine disorders.

Vaginal Microbial Environment Skews Macrophage Polarization and Contributes to Cervical Cancer Development.

As a common female reproductive system malignancy, cervical cancer (CC) disturbs numerous women's health. This study demonstrates the role of the vaginal microbial environment (Peptostreptococcus anaerobius) in cervical cancer. Functional assays, including cell proliferation assay, tube formation assay, and immunofluorescence staining, revealed the effect of Peptostreptococcus anaerobius-treated macrophages on cell proliferation and the angiogenesis process. The tube formation assay disclosed the function of Peptostreptococcus anaerobius-treated macrophages on angiogenesis. In vivo assays were also established to explore the impact of Peptostreptococcus anaerobius-treated macrophages on tumor migration. The results revealed that Peptostreptococcus anaerobius-induced macrophages boosted cervical cancer migration and angiogenesis both in vitro and in vivo. Then, this study unveiled that Peptostreptococcus anaerobius-induced macrophage secreted VEGF to stimulate the angiogenesis in cervical cancer. As a whole, Peptostreptococcus anaerobius-induced macrophage facilitates cervical cancer development through modulation of VEGF expression.

Exosome Mediated Cytosolic Cisplatin Delivery Through Clathrin-Independent Endocytosis and Enhanced Anti-cancer Effect via Avoiding Endosome Trapping in Cisplatin-Resistant Ovarian Cancer.

Background: Ovarian carcinoma is one of the most common gynecologic malignancies, cisplatin resistance has become a key obstacle to the successful treatment of ovarian cancer because ovarian carcinomas are liable to drug resistance. To find an effective drug carrier is an urgent need. Methods: Exosomes and loading-cisplatin exosomes are isolated using differential centrifugation and characterized by transmission, electron, nanoparticle tracking analysis. The anti-cancer effect of cisplatin was detected under the circumstance of delivered by exosomes or without exosomes in vitro and in vivo. Using proteome analysis and bioinformatics analysis, we further discovered the pathways in exosomes delivery process. We employed a con-focal immunofluorescence analysis, to evaluate the effects of milk-exosomes deliver the cisplatin via avoiding endosomal trapping. Results: Exosomes and exosome-cisplatin were characterized including size, typical markers including CD63, Alix and Tsg101. The anti-cancer effect of cisplatin was enhanced when delivered by exosome in vitro and in vivo. Mechanistic studies shown that exosomes deliver cisplatin mostly via clathrin-independent endocytosis pathway. Exosomes deliver cisplatin into cisplatin-resistant cancer cells clathrin-independent endocytosis and enhance the anti-cancer effect through avoiding endosome trapping. Conclusion: Cisplatin could be delivered by exosome through clathrin-independent endocytosis, and could evade the endosome trapping, diffused in the cytosol evenly. Our study clarifies the mechanism of exosomes mediated drug delivery against resistant cancer, indicates that exosomes can be a potential nano-carrier for cisplatin against cisplatin resistant ovarian cancer, which validates and enriches the theory of intracellular exosome trafficking.

Gut and Vaginal Microbiomes in PCOS: Implications for Women's Health.

PCOS is defined as a kind of endocrine and metabolic disorder which affects females at reproductive ages, is becoming much more common, nowadays. Microbiomes are known as microorganisms that inhabit the body to play a vital role in human health. In recent years, several basic and clinical studies have tried to investigate the correlation between the reproductive health/disorder and microbiomes (gut microbiomes and vaginal microbiomes). However, the mechanism is still unclear. In this review, we reviewed the relationship between PCOS and microbiomes, including gut/vaginal microbiomes compositions in PCOS, mechanism of microbiomes and PCOS, and then collectively focused on the recent findings on the influence of microbiomes on the novel insight regarding the therapeutic strategies for PCOS in the future clinical practice.

Contrast Sensitivity Deficits and Its Structural Correlates in Fuchs Uveitis Syndrome.

Purpose: To investigate the deficits in contrast sensitivity in patients with Fuchs uveitis syndrome (FUS) and to explore the potential relationship between contrast sensitivity and ocular structure. Methods: In this prospective study, 25 patients with FUS and 30 healthy volunteers were recruited. Eyes were divided into three groups: FUS-affected eyes (AE), fellow eyes (FE), and healthy eyes. The contrast sensitivity function (CSF) of all participants was evaluated using the quick CSF (qCSF) method. Fundus photographs were collected for the analysis of refractive media, and vascular density (VD) was assessed using optical coherence tomography angiography (OCTA). Data were analyzed and compared using the generalized estimating equation (GEE). Results: The CSF of AE was significantly lower than that of FE and controls, while no significant difference was observed between FE and controls. Contrast sensitivity was negatively correlated with the grade of haze. No significant correlation was found between visual function and VDs in FUS eyes. Conclusions: We found that the CSF of FUS-affected eyes was significantly reduced, and the visual impairment was predominantly caused by the refractive media turbidity.

Prognosis and factors affecting colorectal cancer with ovarian metastasis.

Colorectal cancer is one of the most common malignant tumors. Its incidence has been increasing in recent years, as has the number of cases of ovarian metastasis of colorectal cancer. The prognosis of colorectal cancer with ovarian metastasis is poor, and it is an important cause of death in female patients. A variety of clinicopathological factors were found to be related to the prognosis of patients with colorectal cancer with ovarian metastasis, such as menopausal status, metastasis limited to the pelvis, and tumor differentiation. Tumor genetic characteristics also provide a new perspective for the prognostic evaluation of colorectal cancer with ovarian metastasis. The prognosis of ovarian metastasis is also closely associated with treatment. The major treatment methods are prophylactic oophorectomy, surgical resection of the primary and metastatic lesions, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy and systematic therapy. If feasible, complete surgical resection of the primary and ovarian metastatic macroscopic lesions combined with postoperative chemotherapy might currently be the most effective treatment for improving the prognosis of patients with colorectal cancer with ovarian metastasis. Genetic analysis also provides a theoretical basis for potential targeted therapy and immunotherapy.

Predicting Lymph Node Involvement in Borderline Ovarian Tumors with a Quantitative Model and Nomogram: A Retrospective Cohort Study.

PURPOSE: This study aimed to establish a predictive model for lymph node involvement (LNI) in patients with borderline ovarian tumor (BOT) using clinicopathological factors. PATIENTS AND METHODS: We collected clinical data from consecutive patients who underwent lymphadenectomy for BOT between 2001 and 2018 and analyzed their clinicopathological features. Multivariate logistic regression was used to identify all independent risk factors associated with LNI; these were then incorporated into the prediction model. RESULTS: In total, we included 248 patients with BOT who were undergoing lymphadenectomy. These were divided into a training cohort (n=174) and a validation cohort (n=74). When considering histopathological data, 16 and 5 patients were identified to have LNI in the training and validation cohorts, respectively. Overall, 13.5% (21/156) patients with serous BOT had LNI while 0% (0/92) patients with non-serous BOT had LNI. We identified several predictors of LNI: the largest tumor being ≥ 12.2cm in diameter, the presence of lesions on the ovarian surface, and the presence of pelvic or abdominal lesions. We created a prediction model and nomogram that incorporated these three risk factors for serous BOT. The model achieved good discriminatory abilities of 0.951 and 0.848 when predicting LNI in the training and validation cohorts, respectively. The LNI-predicting nomogram had an area under curve (AUC) of 0.951 and generated well-fitted calibration curves. CONCLUSION: Non-serous BOT may not require lymphadenectomy as part of surgical staging. The individual risk of LNI in patients with serous BOT can be accurately estimated using our prediction model and nomogram. The use of LNI criteria provides a practical way to support the clinician in making an optimal decision relating to surgical scope for patients with BOT.

The Emerging Roles and Therapeutic Potential of Extracellular Vesicles in Infertility.

Infertility is becoming much more common and affects more couples. The past years witnessed the rapid development of the diagnosis and treatment upon infertility, which give numerous coupled more opportunities become parents. Extracellular vesicles are known as nano-sized membrane vesicles to play a major role in intracellular communication. In recent years, several basic and clinical studies have tried to investigate the correlation between the reproductive health/disorder and extracellular vesicles. However, the mechanism is still unclear. In this review, we reviewed the relationship between reproductive physiology and extracellular vesicles, and then collectively focused on the recent findings on the relationship between extracellular and infertility, and its consequent influence on the novel insight regarding the therapeutic strategies for infertility in the future clinical practice.

The Role of graRS in Regulating Virulence and Antimicrobial Resistance in Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of both community- and hospital-associated infections. The antibiotic resistance and virulence characteristics of MRSA are largely regulated by two-component signal transduction systems (TCS) including the graRS TCS. To make a relatively comprehensive insight into graRS TCS in MRSA, the bioinformatics analysis of dataset GSE26016 (a S. aureus HG001 WT strain vs. the ΔgraRS mutant) from Gene Expression Omnibus (GEO) database was performed, and a total of 563 differentially expressed genes (DEGs) were identified. GO analysis revealed that the DEGs were mainly enriched in the "de novo" IMP biosynthetic process, lysine biosynthetic process via diaminopimelate, and pathogenesis; and they were mainly enriched in purine metabolism, lysine biosynthesis, and monobactam biosynthesis in KEGG analysis. WGCNA suggested that the turquoise module was related to the blue module, and the genes in these two modules were associated with S. aureus virulence and infection. To investigate the role of graRS in bacterial virulence, a graRS knockout mutant (ΔgraRS) was constructed using MRSA USA500 2,395 strain as a parent strain. Compared to the wild-type strain, the USA500ΔgraRS showed reduced staphyloxanthin production, retarded coagulation, weaker hemolysis on blood agar plates, and a decreased biofilm formation. These altered phenotypes were restored by the complementation of a plasmid-expressed graRS. Meanwhile, an expression of the virulence-associated genes (coa, hla, hlb, agrA, and mgrA) was downregulated in the ΔgraRS mutant. Consistently, the A549 epithelial cells invasion of the ΔgraRS mutant was 4-fold lower than that of the USA500 wild-type strain. Moreover, on the Galleria mellonella infection model, the survival rate at day 5 post infection in the USA500ΔgraRS group (55%) was obviously higher than that in the USA500 group (20%), indicating graRS knockout leads to a decreased virulence in vivo. In addition, the deletion of the graRS in the MRSA USA500 strain resulted in its increased susceptibilities to ampicillin, oxacillin, vancomycin, and gentamicin. Our work suggests that the graRS TCS plays an important role in regulating S. aureus virulence in vitro and in vivo and modulate bacterial resistance to various antibiotics.

Adipocytes-Derived Extracellular Vesicle-miR-26b Promotes Apoptosis of Cumulus Cells and Induces Polycystic Ovary Syndrome.

Background: Polycystic ovary syndrome (PCOS) is a refractory reproductive disease and also a kind of endocrine and metabolic disease. Adipocyte cells can produce a mass of extracellular vesicles and orchestrate the status of other types cells. The objective of this study was to determine the effects of adipocyte-derived extracellular vesicles-miR-26b on cumulus cells (CCs) and development of PCOS. Methods: The crosstalk mediated by extracellular vesicle-miR-26b between adipocytes and CCs was determined in CC cells co-cultured with mature adipocytes or incubated with extracellular vesicle isolated from mature adipocytes. CCK-8 assay and flow cytometry were conducted in CCs treated with or without extracellular vesicles; microRNA (miRNA) sequencing was conducted for clarifying the key molecular. Hormone levels and ovary ovulation ability were conducted with animal experiment. Results: The results revealed that miR-26b was upregulated in extracellular vesicles derived from mature adipocytes. Adipocyte-derived extracellular vesicles inhibited viability and promoted apoptosis in CCs via targeting JAG1. Furthermore, extracellular vesicles derived from mature adipocyte disrupted the ovary ovulation and impaired the hormone levels. Conclusions: These results identify a novel signaling pathway that adipocytes-derived extracellular vesicles-miR-26b promotes cell apoptosis in CCs and disrupted the ovary ovulation in the development of PCOS. The study indicates that adipose tissue-derived extracellular vesicles-miR-26b may play a key role in the PCOS and also provides insight into developing new therapeutic strategies for PCOS.

Types and viral load of human papillomavirus, and vaginal microbiota in vaginal intraepithelial neoplasia: a cross-sectional study.

BACKGROUND: Human papilloma virus (HPV) infection is an important risk factor for vaginal intraepithelial neoplasia (VAIN). Recent studies have suggested that the microbiome may play a potential role in cervicovaginal diseases. This study aimed to explore the characteristics of the types and viral load of HPV in VAIN, as well as the association between vaginal microbiota and VAIN. METHODS: A total of 176 women, either with VAIN, or without VAIN but with HPV infection were enrolled in the study. Among them, 109 HPV positive cases were qualified for viral load assay. The vaginal microbiota of 122 HPV positive women, who were matched by severity of cervical lesions and menopause status, was determined by 16S ribosomal RNA (16S rRNA) sequencing. RESULTS: The top 5 types of HPV-associated vaginal lesions were HPV16 (24.2%), HPV52 (24.2%), HPV53 (16.1%), HPV58 (14.5%) and HPV66 (14.5%). The viral load of HPV types 16, 52, and 58 appeared higher in separate vaginal lesions than in histopathologically normal cases (P=0.026, 0.002, and 0.013, respectively). The vaginal microbiota of HPV-positive patients with VAIN did not exhibit a large change in diversity. Vaginal microbiota of VAIN was characterized by an increased abundance of Atopobium, Gardnerella, Allobaculum and Clostridium, as well as decreased abundance of Finegoldia, Actinobaculum and Blautia. A higher level of Enterococcus and some specific Clostridium spp. might be associated with an elevated risk of VAIN2/3. CONCLUSIONS: A higher level of viral load of HPV16, 52, and 58 may indicate VAIN. The composition of vaginal microbiota changes during the progression of VAIN and specific bacteria such as Atopobium, Gardnerella, Allobaculum, Enterococcus and Clostridium, may help to promote its development.

Expanding the Phenotypic and Genotypic Landscape of Nonsyndromic High Myopia: A Cross-Sectional Study in 731 Chinese Patients.

Purpose: High myopia (HM) is defined as a refractive error worse than -6.00 diopter (D). This study aims to update the phenotypic and genotypic landscape of nonsyndromic HM and to establish a biological link between the phenotypic traits and genetic deficiencies. Methods: A cross-sectional study involving 731 participants varying in refractive error, axial length (AL), age, myopic retinopathy, and visual impairment. The phenotypic traits were analyzed by four ophthalmologists while mutational screening was performed in eight autosomal causative genes. Finally, we assessed the clinical relevance of identified mutations under the guidance of the American College of Medical Genetics and Genomics. Results: The relationship between refractive error and AL varied in four different age groups ranging from 3- to 85-years old. In adult groups older than 21 years, 1-mm increase in AL conferred 10.84% higher risk of pathologic retinopathy (Category ≥2) as well as 7.35% higher risk of low vision (best-corrected visual acuities <0.3) with P values < 0.001. The prevalence rates of pathologic retinopathy and low vision both showed a nonlinear positive correlation with age. Forty-five patients were confirmed to harbor pathogenic mutations, including 20 novel mutations. These mutations enriched the mutational pool of nonsyndromic HM to 1.5 times its previous size and enabled a statistically significant analysis of the genotype-phenotype correlation. Finally, SLC39A5, CCDC111, BSG, and P4HA2 were more relevant to eye elongation, while ZNF644, SCO2, and LEPREL1 appeared more relevant to refracting media. Conclusions: Our findings shed light on how multiple HM-related phenotypes are associated with each other and their link with gene variants.

The Controversy, Challenges, and Potential Benefits of Putative Female Germline Stem Cells Research in Mammals.

The conventional view is that female mammals lose their ability to generate new germ cells after birth. However, in recent years, researchers have successfully isolated and cultured a type of germ cell from postnatal ovaries in a variety of mammalian species that have the abilities of self-proliferation and differentiation into oocytes, and this finding indicates that putative germline stem cells maybe exist in the postnatal mammalian ovaries. Herein, we review the research history and discovery of putative female germline stem cells, the concept that putative germline stem cells exist in the postnatal mammalian ovary, and the research progress, challenge, and application of putative germline stem cells in recent years.