Effect of peroxiredoxin 1 on the regulation of trophoblast function by affecting autophagy and oxidative stress in preeclampsia.

PURPOSE: PE is a pregnancy-specific syndrome and one of the main causes of maternal, fetal, and neonatal mortality. PRDX1 is an antioxidant that regulates cell proliferation, differentiation, and apoptosis. The aim of this study is to investigate the effect of PRDX1 on the regulation of trophoblast function by affecting autophagy and oxidative stress in preeclampsia. METHODS: Western blotting, RT-qPCR, and immunofluorescence were used to examine the expression of PRDX1 in placentas. PRDX1-siRNA was transfected to knockdown PRDX1 in HTR-8/SVneo cells. The biological function of HTR-8/SVneo cells was detected by wound healing, invasion, tube formation, CCK-8, EdU, flow cytometry, and TUNEL assays. Western blotting was used to detect the protein expression of cleaved-Caspase3, Bax, LC3II, Beclin1, PTEN, and p-AKT. DCFH-DA staining was used to detect ROS levels by flow cytometry. RESULTS: PRDX1 was significantly decreased in placental trophoblasts in PE patients. Following the exposure of HTR-8/SVneo cells to H2O2, PRDX1 expression was significantly decreased, LC3II and Beclin1 expression was notably increased, and ROS level was also markedly increased. PRDX1 knockdown impaired migration, invasion, and tube-formation abilities and promoted apoptosis, which was accompanied by an increased expression of cleaved-Caspase3 and Bax. PRDX1 knockdown induced a significant decrease in LC3II and Beclin1 expression, along with an elevated p-AKT expression and a decreased PTEN expression. PRDX1 knockdown increased intracellular ROS levels, and NAC attenuated PRDX1 knockdown-induced apoptosis. CONCLUSION: PRDX1 regulated trophoblast function through the PTEN/AKT signaling pathway to affect cell autophagy and ROS level, which provided a potential target for the treatment of PE.

Assessment of the association between prenatal exposure to multiple ambient pollutants and preterm birth: A prospective cohort study in Jinan, east China.

Air pollution has been documented with a series of adverse pregnancy outcomes, yet their reproductive and developmental toxicity on human beings has not been fully elucidated. Here, we analyzed the geographic distribution of Jinan and examined its contribution to air pollution. After adjusting demographic variables and environmental co-pollutants, we built statistical models based on 424 couples and checked different air pollutants on their pregnancy outcomes. We find that Jinan is tightly surrounded by mountains from 3 of 4 sides, geographically resulting in a typical basin texture that hinders the diffusion of ambient pollutants. Of 424 pregnant women enrolled in this study, 17 subjects were diagnosed with preterm birth. Using air quality index (AQI) as an integrated indicator of PM10, PM2.5, SO2, NO2, CO, and O3, we found that each interquartile range (IQR) increase in AQI was associated with 11% increased odds of preterm birth. Also, elevating PM2.5, PM10, SO2, and O3 led to different increased risk levels of preterm birth. By running the generalized additive model analyses, the association of AQI and preterm birth was further confirmed. In conclusion, based on samples in Jinan, east China, prenatal exposure to multiple ambient pollutants is associated with reduced gestational age and increased risk of preterm birth.

Suppression of FPR2 expression inhibits inflammation in preeclampsia by improving the biological functions of trophoblast via NF-κB pathway.

PURPOSE: The dysfunction of trophoblast during inflammation plays an important role in PE. Formyl peptide receptor 2 (FPR2) plays crucial roles in the development of inflammation-associated disease. This present study aimed to explore the effect of FPR2 on a trophoblast cellular model of preeclampsia. METHODS: The expression of FPR2 in placenta was detected by immunohistochemical staining and western blotting. Transfection of siRNA was used to knockdown FPR2 in HTR-8/SVneo cells. Inflammatory cytokines were detected by ELISA. CCK8, Transwell, wound healing, FACS and tube formation assays were performed to observe the abilities of cell proliferation, migration, invasion, apoptosis and angiogenesis. Western blotting was implemented to clarify that NF-κB signaling pathway was downstream of FPR2. RESULTS: The expression levels of FPR2 were higher in placental tissues of patients with PE. Knockdown of FPR2 expression by siFPR2 or inhibition of its activity by WRW4 decreased the release of proinflammatory cytokines in HTR8/SVneo cells treated with LPS. Knockdown of FPR2 expression or inhibition of its activity further reversed the LPS-induced attenuation of the proliferation, migration, invasion and angiogenesis and increase in apoptosis in HTR8/SVneo cells. Moreover, the NF-κB signaling pathway was activated in both placental tissues of patients with PE and LPS-treated HTR8/SVneo cells. However, the activation was attenuated when FPR2 was knocked down or inhibited. CONCLUSION: Suppression of FPR2 expression alleviated the effects of inflammation induced by LPS on trophoblasts via the NF-κB signaling pathway, which provided a novel and potential strategy for the treatment of PE.

Effect of RvD1/FPR2 on inflammatory response in chorioamnionitis.

Chorioamnionitis (CAM), as a common intrauterine infectious disease, is the leading cause of premature birth, stillbirth, neonatal infection and sepsis. The formyl peptide receptor 2 (FPR2) is a member of GPCRs widely distributed in a variety of tissues and is associated with many inflammatory diseases. With the discovery of FPR2 in human placenta, the possibility of exploring the function of FPR2 in obstetrics is evolving. The Resolvin D1 (RvD1) plays an important role in the resolution of inflammation by combining with FPR2. In this study, we evaluated the role of FPR2 and RvD1 in CAM, not only in the human placenta but also in mouse models. The expression of FPR2 increased in the placenta of CAM patients and the downstream PPARγ/NF-κB signalling changed accordingly. Moreover, Fpr2-/- mice were highly susceptible to LPS, displaying a worse CAM symptom, compared with WT mice. By establishing a model of trophoblast inflammation in vitro, it was confirmed that RvD1 rescued the effect of LPS on inflammation by combining with FPR2 and its downstream PPARγ/NF-κB pathway. Otherwise, RvD1 improved the preterm labour in a mouse model of CAM induced by LPS. Altogether, these findings show that RvD1 alleviated the inflammation of trophoblast in vivo and in vitro through FPR2/PPARγ/NF-κB pathway, suggesting RvD1/FPR2 might be a novel therapeutic strategy to alleviate CAM.

Effect of scrotal heating on sperm quality, seminal biochemical substances, and reproductive hormones in human fertile men.

At present, male contraceptive methods are only vasectomy and condoms, so it is necessary to research on male contraceptive techniques. The aim of this study is to observe the effects of scrotal heating (SH) on semen parameters, seminal l-carnitine (LC), epidermal growth factor (EGF), macrophage migration inhibitory factor (MIF), reproductive hormones and sperm chromosome numbers of adult healthy men, and to provide the experimental data for male contraception. The scrotums of 30 healthy male volunteers were exposed to the condition of 40 to 43°C SH belt warming 40 minutes each day for successive 2 days per week. The course of SH was continuous for 3 months. Computer-assisted semen analysis and hypo-osmotic swelling test, sperm DNA integrity, l-carnitine, MIF and EGF, and sperm fluorescence in situ hybridization were performed before, during, and after SH. The serum level of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) were measured by chemiluminescent immunoassay. The mean parameters of sperm concentration, vitality, and normal morphological sperm were significantly decreased in groups with sperms being collected during 1, 2, and 3 months of SH when compared with those in groups of pre-SH (P < 0.01). Statistically significant differences of sperm DNA fragmentation, normal sperm membrane functionality, levels of LC and MIF in semen, and LH, FSH, and T in serum were observed between the groups of before SH and after SH 3 months and the groups of during SH 1, 2, and 3 months (P < 0.001). The total rate of chromosome number for 13, 18, 21, X, and Y in the 3 months of SH was 13.7-fold greater (13.72%/1.69%) than before SH (P < 0.001). The constant SH can impact the semen quality, sperm DNA integrity, sperm chromosome, LC and MIF, and LH, FSH, and T in serum. Transient SH may be a new method for male contraception.

[Yam polysaccharide improves sperm viability and protects sperm DNA integrity in vitro].

OBJECTIVE: To clarify the roles of yam polysaccharide (YPS) in improving sperm viability and protecting sperm DNA integrity in vitro and provide a new approach to the treatment of oligoasthenozoospermia. METHODS: We collected samples by masturbation from 36 normal fertile males aged 27－39 years. Each sample was divided into six groups: blank control or treated with normal saline, vitamin C solution, and YPS solution at low (0.25 mg/ml), medium (1.0 mg/ml) or high concentration (5.0 mg/ml). Using eosin-Y staining, sperm hypotonic swelling (HOS) and sperm chromatin diffusion (SCD) test, we observed the effects of different concentrations of YPS on sperm viability, membrane integrity and nuclear DNA. RESULTS: After 24 and 48 hours of treatment, sperm viability was markedly reduced in the vitamin C (ï¼»28.5 ± 3.1ï¼½ and ï¼»6.5 ± 1.2ï¼½%), low-YPS (ï¼»31.3 ± 3.5ï¼½ and ï¼»6.5 ± 2.2ï¼½%), medium-YPS (ï¼»37.1 ± 3.5ï¼½ and ï¼»9.5 ± 2.8ï¼½%) and high-YPS groups (ï¼»38.3 ± 3.3ï¼½ and ï¼»9.0 ± 3.2ï¼½%) as compared with the blank control (ï¼»17.3 ± 2.1ï¼½ and ï¼»3.2 ± 1.3ï¼½%) (P <0.01) and normal saline groups (ï¼»13.4 ± 4.1ï¼½ and ï¼»3.1 ± 2.0ï¼½%) (P <0.01), and it was significantly higher in the medium- and high-YPS than in the vitamin C group (P <0.05 and P <0.01). The rate of sperm DNA fragmentation was remarkably decreased at 48 hours in the vitamin C (ï¼»30.5 ± 3.1ï¼½%), low-YPS (ï¼»29.4 ± 2.6ï¼½%), medium-YPS (ï¼»28.5 ± 2.3ï¼½%) and high-YPS groups (ï¼»27.9 ± 1.9ï¼½%) in comparison with the blank control (ï¼»41.7 ± 2.2ï¼½%) (P <0.01) and normal saline groups (ï¼»42.1 ± 3.3ï¼½%), markedly lower in the medium- and high-YPS than in the blank control, normal saline and vitamin C groups (P <0.05 or P <0.01), but with no statistically significant difference between the low-YPS and vitamin C groups (P >0.05). CONCLUSIONS: Yam polysaccharide can improve sperm viability and protect sperm DNA integrity in vitro.

Ferroptosis is involved in trophoblast cells cytotoxicity induced by black phosphorus nanoparticles.

Black phosphorus (BP) is a new type of nanomaterial, which has been widely used in many biomedical fields due to its superior properties, but there are few studies on the toxicity of BP, especially in the reproductive system. To explore the effects of BP exposure on reproduction and reveal its molecular mechanism, we firstly investigated the potential toxicity of black phosphorus nanoparticles (BPNPs) in vivo. The results showed that BP exposure in pregnant mice can reduce the weight of fetal mice and placenta. H&E staining further indicated the changes of placental cross-section and vascular remodeling after BP treatment. Then, human exvillous trophoblast HTR8/SVneo was treated with different concentrations of BPNPs. We found that BPNPs induced significant cytotoxicity, including dose-dependent reduction of cell viability and proliferation. Trophoblast cell migration and invasion were also impaired by BPNPs exposure. Moreover, pretreatment with Cytochalasin D (Cyto-D), a classical phagocytic inhibitor, alleviated the decline of cell viability induced by BPNPs. Transcriptome sequencing showed that BPNPs exposure led to ferroptosis. Subsequently, the related indexes of ferroptosis were detected, including increase of iron ion concentration, decrease of the ferroptosis marker, GPX4 (Glutathione Peroxidase 4), increase of FTL (Ferritin Light Chain), and increase of lipid peroxidation indexes (MDA level and decrease of GSH level). In addition, ferroptosis inhibitors (Fer-1 and DFO) pretreatment can alleviate both the cytotoxic effects and functional impairment induced by BPNPs. In summary, our study confirmed the reproductive toxicity of BPNPs for the first time, and constructed BPNPs injury model in vitro using human villus trophoblast cells and revealed the role of ferroptosis in this process, which deepened our understanding of the biosafety of black phosphorus nanomaterials.

Pcgf5: An important regulatory factor in early embryonic neural induction.

Polycomb group RING finger (PCGF) proteins, a crucial subunits of the Polycomb complex, plays an important role in regulating gene expression, embryonic development, and cell fate determination. In our research, we investigated Pcgf5, one of the six PCGF homologs, and its impact on the differentiation of P19 cells into neural stem cells. Our findings revealed that knockdown of Pcgf5 resulted in a significant decrease in the expression levels of the neuronal markers Sox2, Zfp521, and Pax6, while the expression levels of the pluripotent markers Oct4 and Nanog increased. Conversely, Pcgf5 overexpression upregulated the expression of Sox2 and Pax6, while downregulating the expression of Oct4 and Nanog. Additionally, our analysis revealed that Pcgf5 suppresses Wnt3 expression via the activation of Notch1/Hes1, and ultimately governs the differentiation fate of neural stem cells. To further validate our findings, we conducted in vivo experiments in zebrafish. We found that knockdown of pcgf5a using morpholino resulted in the downregulated expression of neurodevelopmental genes such as sox2, sox3, and foxg1 in zebrafish embryos. Consequently, these changes led to neurodevelopmental defects. In conclusion, our study highlights the important role of Pcgf5 in neural induction and the determination of neural cell fate.

[Corrigendum] FPR2 serves a role in recurrent spontaneous abortion by regulating trophoblast function via the PI3K/AKT signaling pathway.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the '0 h/si-NC + Solvent' and '0 h/si-FPR2 + Solvent' data panels shown in Fig. 4B on p. 7 appeared to contain overlapping sections of data, such that they were potentially derived from the same original source where these panels was intended to show the results from differently performed experiments. After having conducted an independent investigation of the figures in the Editorial Office, it was identified that sections of the 'si-NC + Solvent' and 'si-FPR2 + LY294002' data panels in Fig. 4C also contained overlapping data. After having asked the authors to provide an explanation of these data, they realized that this figure was inadvertently assembled incorrectly. They were, however, able to consult their original data, and the revised version of Fig. 4, containing the correct data panel for the 'si-FPR2 + LY294002' experiment in Fig. 4C and complete data from one of the alternatively performed experiments in Fig. 4B, is shown on the next page. Note that these errors did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 24: 838, 2021; DOI: 10.3892/mmr.2021.12478].

TIGAR deficiency induces caspase-1-dependent trophoblasts pyroptosis through NLRP3-ASC inflammasome.

Introduction: Gestational diabetes mellitus (GDM), a common complication of pregnancy, is risky for both mother and fetus. Previous studies about TP53-induced glycolysis and apoptosis regulator (TIGAR) focused on the occurrence and development of cancer, cardiovascular disease, and neurological disease, however, it is still unclear whether TIGAR plays a regulatory role in gestational diabetes mellitus (GDM). Methods: Utilizing HG exposure, we explored the role of TIGAR in oxidative stress limitation, excessive inflammatory toxicity defense, and pyroptosis prevention. Results: TIGAR was up-regulated in vivo and in vitro under HG condition, and loss of TIGAR increased ROS in trophoblast cells which drove a phenotypic switch and hindered the capacity of migration, invasion, and tube formation. This switch depended on the increased activation of NLRP3-ASC-caspase-1 signaling, which caused a distinctive characteristic of pyroptosis, and these findings could finally be reverted by antioxidant treatment (NAC) and receptor block (MCC950). Collectively, trophoblast pyroptosis is an upstream event of TIGAR deficiency-induced inflammation, which is promoted by ROS accumulation through NLRP3-ASC inflammasome. Conclusion: Taken together, our results uncovered that, as the upstream event of TIGAR deficiency-induced inflammation, pyroptosis is stimulated by ROS accumulation through NLRP3-ASC inflammasome.

PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis.

Epidemiological studies have demonstrated that fine particulate matter (PM2.5) is associated with adverse obstetric and postnatal metabolic health outcomes, but the mechanism remains unclear. This study aimed to investigate the toxicological pathways by which PM2.5 damaged placental trophoblasts in vivo and in vitro. We confirmed that PM2.5 induced adverse gestational outcomes such as increased fetal mortality rates, decreased fetal numbers and weight, damaged placental structure, and increased apoptosis of trophoblasts. Additionally, PM2.5 induced dysfunction of the trophoblast cell line HTR8/SVneo, including in its proliferation, apoptosis, invasion, migration and angiogenesis. Moreover, we comprehensively analyzed the transcriptional landscape of HTR8/SVneo cells exposed to PM2.5 through RNA-Seq and observed that PM2.5 triggered overexpression of pathways involved in oxidative stress and mitochondrial apoptosis to damage HTR8/SVneo cell biological functions through CYP1A1. Mechanistically, PM2.5 stimulated KLF9, a transcription factor identified as binding to CYP1A1 promoter region, which further modulated the CYP1A1-driven downstream phenotypes. Together, this study demonstrated that the KLF9/CYP1A1 axis played a crucial role in the toxic progression of PM2.5 induced adverse pregnancy outcomes, suggesting adverse effects of environmental pollution on pregnant females and putative targeted therapeutic strategies.

6-Gingerol alleviates placental injury in preeclampsia by inhibiting oxidative stress via BNIP3/LC3 signaling-mediated trophoblast mitophagy.

Background and aims: Preeclampsia (PE) is the leading cause of maternal and fetal morbidity and mortality worldwide. Apoptosis of trophoblast cells induced by oxidative stress is a principal reason of placental injury in PE. 6-Gingerol, an antioxidant from ginger, plays an important role in many disease models, but its effect on obstetric diseases has not been elucidated. In this study, we investigated the protective effect of 6-gingerol against placental injury. Methods: In vitro hypoxia/reoxygenation (H/R) model of HTR8/Svneo cells and preeclamptic mice model were established to simulate PE. The effects of 6-Gingerol on PE were evaluated by morphological detection, biochemical analysis, and Western blot. Results: We found that H/R treatment induced cell apoptosis, increased the production of reactive oxygen species, malondialdehyde and lactate dehydrogenase, and decreased superoxide dismutase in trophoblast. In addition, the polarization of mitochondrial membrane potential and the cellular calcium flux were also destroyed under H/R condition, which also activated BCL2-interacting protein 3 (BNIP3) and provoked excessive mitophagy. Importantly, 6-Gingerol reversed these corrosive effects. Furthermore, the placenta damage in PE-like mouse caused by the cell apoptosis, oxidative stress and mitophagy was mitigated by 6-Gingerol. Conclusion: These findings suggest that 6-Gingerol exerts a protective effect against placental injury in PE by reducing oxidative stress and inhibiting excessive mitophagy caused by mitochondrial dysfunction.

Proteomic analysis of amniotic fluid to identify potential targets predicting preterm delivery.

Preterm delivery is a common complication of pregnancy which leads to significant neonatal mortality and morbidity. Identifying predictive markers linked to spontaneous preterm delivery (SPTD) is important for effective treatment and prevention of PTD. To explore potential biomarkers related to SPTD, we performed proteomics analysis in amniotic fluid (AF). In total, we enrolled 30 pregnant women with singleton gestation who underwent clinically indicated amniocentesis at 15-24 weeks of gestation. LC-MS analysis was used to analyze the AF samples of 10 women with SPTD < 34 weeks after cervix cerclage (Preterm group), 10 women with term delivery (TD) ≥ 34 weeks after cervix cerclage (Term group), and 10 women who delivered at term (Normal group). ELISA validation was performed for candidate proteins in a second independent cohort. As a result, we identified 44 differentially expressed proteins (DEPs, P < 0.05) via proteomic analysis, and based on that, 9 primary pathways were also determined in SPTD. Results of the ELISA assay confirmed that the increased concentration of Serpin A1, decreased concentrations of Renin and IGFBP4 were significantly associated with SPTD at ≤34 weeks.

Predicting the risk of fetal macrosomia at pregnancy in Shandong province: a case-control study.

BACKGROUND AND AIM: Macrosomia is used to describe an infant born with excessively high weight, and it brings lots of unexpected risks in clinical work. Macrosomia causes considerable challenges for both physicians and pregnant women. Our objectives were to identify factors in gravida to be associated with the risk of macrosomia, to guide clinical prevention and treatment. METHODS: The study assessed risk factors of macrosomia by comparison with normal birth weight neonates, and a case-control study was conducted at Shandong Provincial Maternity and Child Healthcare Hospital. We followed and selected the relevant indicators of gravida who gave birth to macrosomia or normal infants, and applied statistical analysis to identify clinical indicators related to macrosomia. RESULTS: Maternal blood glucose (OR 3.88 (1.07, 14.15)), history of abnormal conception (OR 18.44 (1.05, 322.89)), situation of menarche (OR 13.53 (1.28, 142.66)), and menstrual cycle of gravida (OR 13.24 (1.17, 150.24)) were significant influencing factors of macrosomia, but did not appear in the univariate analysis. Adding gestational age at delivery (OR 4.00 (1.45, 11.09)), triglyceride (OR 0.01 (<0.01, 0.40)), and MBI (OR 46.35 (2.08, >99.99)) of pregnant women, the area under the curve (AUC) curve was drawn for forecasting the risk of macrosomia, and the value of AUC was 0.9174. The triglyceride blood index of pregnant women was the only one that was inversely proportional to the probability of giving birth to macrosomic infants. The low-density lipoprotein (LDL) (OR 0.29 (0.12, 0.72)) and total cholesterol (OR 0.39 (0.20, 0.75)) were important factors in univariate analysis, and both of them were negative correlation factors of macrosomia. All influencing factors in multivariate analysis were selected for drawing a receiver operating characteristic (ROC) curve, and the value of the AUC was 0.9174. CONCLUSIONS: This analysis could therefore accurately predict the risk of pregnant women who would deliver macrosomic infants.

FPR2 serves a role in recurrent spontaneous abortion by regulating trophoblast function via the PI3K/AKT signaling pathway.

Recurrent spontaneous abortion (RSA) effects both the physical and mental health of women of reproductive age. Trophoblast dysfunction may result in RSA due to shallow placental implantation. The mechanisms underlying formyl peptide receptor 2 (FPR2) on the biological functions of trophoblasts remain to be elucidated. The present study aimed to explore the potential functions of FPR2, a G protein­coupled receptor, in placental trophoblasts. The location and expression levels of FPR2 in the villi tissue of patients with RSA were detected using immunohistochemical staining, reverse transcription­quantitative PCR and western blotting. Following the transfection of small interfering RNA targeting FPR2 in HTR­8/SVneo cells, a Cell Counting Kit­8 assay was used to determine the levels of cell viability. Flow cytometry was used to examine the levels of cell apoptosis and gap closure and Transwell assays were carried out to evaluate the levels of cell migration and invasion. A tube formation assay was performed to detect the levels of capillary­like structure formation. Western blotting was used to detect the expression levels of proteins in the associated signaling pathways. The expression of FPR2 was present in villi trophoblasts and was markedly increased in patients with RSA. The levels of trophoblast invasion, migration and tube formation were markedly increased following FPR2 knockdown, whereas the levels of apoptosis were markedly decreased. In addition, FPR2 knockdown caused an increase in the phosphorylation levels of AKT and PI3K. Thus, FPR2 may be involved in the regulation of trophoblast function via the PI3K/AKT signaling pathway. The results of the present study provided a theoretical basis for the use of FPR2 as a target for the treatment of trophoblast­associated diseases, such as RSA.

Improved placental vascular repair in a rat preeclampsia model by implantation of endothelial progenitor cells treated with platelet microparticles.

Objective: To detect the role of endothelial progenitor cells (EPCs) treated with platelet microparticles (PMPs) in preeclampsia. Methods: EPCs treated with/without PMPs were labeled and injected to PE rats. The differentiation of EPCs, the change of endothelial nitric oxide synthase (eNOS), blood pressure and proteinuria were measured. The blood pressure and proteinuria increased in each of PE groups, and were improved by EPCs which was strengthened by PMPs. Transplantation of EPCs increased placental angiogenesis. The trend of change of NO was the same as blood pressure. Conclusion: Transplantation of EPCs treated with PMPs improved blood pressure and proteinuria more effectively.

Comprehensive characterization of endometrial competing endogenous RNA network in infertile women of childbearing age.

Endometriosis is widely associated with infertility in women of childbearing age, for which there have been no effective treatments. Recent studies suggest that the dysregulation of RNAs contributes to the pathogenesis of endometriosis, so we conduct the case-control genetic analysis to characterize the expression and interaction of different subtypes of RNAs in infertile women with endometriosis. The ectopic and eutopic endometrium of patients undergoing infertility treatment were collected and subjected to high throughput sequencing, and bioinformatics analysis was conducted to construct the competing endogenous RNA (ceRNA) network. As a result, the RNA interactive network was constructed in endometriosis, and a set of mRNAs such as cyclin-dependent kinase 1 (CDK1) and proliferating cell nuclear antigen (PCNA) along with their corresponding miRNAs and lncRNAs were found to promote the growth and death of endometrial stromal cells, which was essential for the pathogenesis of endometriosis. These data suggest that RNA crosstalk is a crucial segment in the development of endometriosis, where CDK1 and PCNA may serve as emerging targets for the treatment of endometriosis-related infertility in women of childbearing age.

Mechanism of PM2.5-induced human bronchial epithelial cell toxicity in central China.

Exposure to PM2.5 has been linked to respiratory disorders, yet knowledge of the molecular mechanism is limited. Here, PM2.5 was monitored and collected in central China, and its cytotoxicity mechanism on human bronchial epithelial cells (BEAS-2B) was investigated. With the average concentration of 109 ±â€¯69 µg/m3, PM2.5 was rich in heavy metals and organic pollutants. After exposure to PM2.5, the viability of BEAS-2B cells decreased, where 510 dysregulated genes were predicted to induce necroptosis via inhibiting ATP synthesis through the oxidative phosphorylation signaling pathway. Cellular experiments demonstrated that the content of ATP was downregulated, while the expression of RIP3, a necroptosis indicator, was upregulated. Besides, four enzymes in charge of ATP synthesis were downregulated, including ATP5F, NDUF, COX7A, and UQCR, while two genes of RELA and CAPN1 responsible for necroptosis were upregulated. Furthermore, N-acetylcysteine was applied as an enhancer for ATP synthesis, which reversed the downregulation of ATP5F, NDUF, and COX7A, and consequently alleviated the elevation of RELA, CAPN1, and RIP3. In conclusion, PM2.5 exposure downregulates ATP5F, NDUF, COX7A, and UQCR, and that inhibits ATP synthesis via the oxidative phosphorylation signaling pathway, which subsequently upregulates RELA and CAPN1 and ultimately leads to necroptosis of BEAS-2B cells.

Biologic response of sperm and seminal plasma to transient testicular heating.

Currently, there are few male contraceptive methods that are purely based on prevention of the entry of the sperm into the female reproductive tract. An alternative approach for designing reversible male contraceptive is achieved by transient testicular heating (TTH). This treatment, through massive germ cell apoptosis, causes reversible oligospermia or azoospermia. Here, we describe as how TTH causes DNA damage, oxidative stress, apoptosis, autophagy, sperm protein expression, and alters the biochemical components of seminal plasma. Further understanding of TTH will help design safe and reversible male contraception.