Association between blood lead levels and unfavorable IVF outcomes: potential involvement of endoplasmic reticulum stress response in granulosa cells.

PURPOSE: To investigate the relationship between blood lead levels (BLLs) and IVF clinical outcomes in infertile females and to further explore the possible involvement of granulosa cell (GC) endoplasmic reticulum (ER) stress in the process. METHODS: One hundred twenty-three infertile women undergoing IVF cycles were included in the current study. All participants were divided into three (low, medium, and high) groups determined by BLL tertiles. Gonadotropin releasing hormone (GnRH) agonist regimen for ovarian stimulation was used for all patients, with follicular fluids being collected on the day of oocyte retrieval. Lactate dehydrogenase (LDH) levels in follicular fluid and the endoplasmic reticulum stress-signaling pathway of granulosa cells (GCs) were examined. RESULTS: The oocyte maturation rate and high-quality embryo rate on cleaved stage decreased significantly as BLL increased. For lead levels from low to high, live birth rate (68.29%, 56.10%, 39.02%; P=0.028) showed negative correlations with BLLs. Also, follicular fluid Pb level and LDH level was significantly higher in the high lead group versus the low group. Binomial regression analysis revealed significant negative correlation between BLLs and live birth rate (adjusted OR, 0.38; 95% CI, 0.15-0.95, P=0.038). Further analysis of the endoplasmic reticulum stress (ER stress) signaling pathway of GCs found that expressions of GRP78, total JNK, phosphorylated JNK, and CHOP increased and BCL-2 decreased with increasing BLLs. CONCLUSIONS: BLLs are negatively associated with final clinical outcomes in IVF patients that may be related to increased ER stress response and GC apoptosis. Thus, reducing Pb exposure before IVF procedures may improve final success rates.

High glucose regulates the cells dysfunction of human trophoblast HTR8/SVneo cells by downregulating GABRP expression.

BACKGROUND: In response to the high-glucose environment in patients with gestational diabetes mellitus (GDM), trophoblast cells undergo a series of pathological changes. Gamma-aminobutyric acid type A receptor subunit pi (GABRP) is involved in the development of pregnancy-related diseases and regulation of blood glucose. OBJECTIVES: To explore the relationship between GABRP and hyperglycemia stimulation in GDM patients, and to provide preliminary experimental evidence for whether GABRP has the potential as a molecular target for the treatment of GDM. MATERIAL AND METHODS: Within 30 min after birth, placental samples were taken from 20 GDM patients and 20 pregnant women without GDM. Human chorionic trophoblast HTR-8/SVneo cells were utilized for in vitro experimental investigation. We explored changes in GABRP expression in placental samples and HTR-8/Svneo cells using western blot and quantitative reverse transcription polymerase chain reaction (RT-qPCR). Cells in the high-glucose treatment group were exposed to medium containing 25 mM glucose. To explore the relationship between GABRP and high-glucose stimulation, GABRP was overexpressed in HTR-8/SVneo cells. We monitored the cell viability, invasion and migration abilities using Cell Counting Kit-8 (CCK-8), transwell and scratch assays, respectively. RESULTS: We found that GABRP expression was significantly reduced in placental samples from GDM patients. Furthermore, high-glucose treatment decreased the expression level of GABRP in HTR-8/SVneo cells. High-glucose stimulation reduced the cell viability, invasion and migration abilities. GABRP overexpression reversed the biological dysfunction of the cells induced by high-glucose stimulation. CONCLUSIONS: Hyperglycemia in GDM patients downregulates the expression of GABRP, and overexpression of GABRP promotes the viability, migration and invasive ability of HTR8-/SVneo cells.

Serum miR-195-5p is upregulated in gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is defined as varying degrees of glucose intolerance with an onset or first recognition during pregnancy in women without previously diagnosed diabetes. Accumulating evidence indicates that miRNAs exert crucial roles in the pathogenesis and development of diabetes, including GDM. In the present study, we aimed to determine the clinical performance of miR-195-5p in GDM. METHODS: First, the miR-195-5p expressions in serum samples from healthy pregnant women and women with GDM at 25 weeks pregnancy were detected using real-time polymerase chain reaction (RT-qPCR). Then, receive characteristic (ROC) curve was used to determine the diagnostic value of miR-195-5p in GDM. Finally, the correlation analysis of miR-195-5p expression with related clinicopathological factors was carried out to determine the clinical value of miR-195-5p in GDM. RESULTS: In this study, we found that miR-195-5p expression was significantly increased in serum samples from GDM patients as compared with that in healthy pregnancies. Furthermore, miR-195-5p might be a putative biomarker for GDM diagnosis with an area under the curve (AUC) of 0.8451; the cutoff value was 1.598, sensitivity was 73.69%, specificity was 96.85%, accuracy was 81.26%, and Youden index was 70.54%. Expression of miR-195-5p was positively associated with fasting plasma glucose, one-hour plasma glucose, and two-hour plasma glucose. CONCLUSION: miR-195-5p might function as a putative diagnostic biomarker for GDM and contribute to identifying at-risk mothers in pregnancy.

Predictive value of maternal serum NF-κB p65 and sTREM-1 for subclinical chorioamnionitis in premature rupture of membranes.

PROBLEM: The aim of this study was to investigate the levels of nuclear factor kappa B-p65 (NF-κB p65) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in maternal blood with premature rupture of membranes (PROM) and to assess their values for prediction of subclinical chorioamnionitis. METHOD: NF-κB p65 and sTREM-1 levels were measured in maternal blood and cord blood by fluorescence quantitative RT-PCR assay. According to the placental membranes pathological examination, pregnant women with PROM were divided into chorioamnionitis group (n=28) and non-chorioamnionitis group (n=22). RESULTS: In the PROM group,the NF-κB p65 and sTREM-1 levels in maternal blood were significantly higher in women with chorioamnionitis than women without chorioamnionitis (P<.05). The cutoff value of maternal NF-κB p65, sTREM-1, C-reactive protein (CRP), and WBC level were 6.73, 2.93, 6.75 mg/L, and 10.8×10(9) /L, respectively, through analysis of the area under the ROC curve (AUC). The optimal combination test was detection of maternal blood NF-κB p65 and CRP levels, which resulted in a sensitivity of 89.3% and a specificity of 72.7% for the prediction of subclinical chorioamnionitis. CONCLUSION: Combined measurements of maternal NF-κB p65 and CRP levels may be used as early biological indicators that predict subclinical chorioamnionitis in premature rupture of membranes.