ChIP-seq and RNA-seq Reveal the Involvement of Histone Lactylation Modification in Gestational Diabetes Mellitus.

Lactylation is a novel post-translational modification of proteins. Although the histone lactylation modification has been reported to be involved in glucose metabolism, its role and molecular pathways in gestational diabetes mellitus (GDM) are still unclear. This study aims to elucidate the histone lactylation modification landscapes of GDM patients and explore lactylation-modification-related genes involved in GDM. We employed a combination of RNA-seq analysis and chromatin immunoprecipitation sequencing (ChIP-seq) analysis to identify upregulated differentially expressed genes (DEGs) with hyperhistone lactylation modification in GDM. We demonstrated that the levels of lactate and histone lactylation were significantly elevated in GDM patients. DEGs were involved in diabetes-related pathways, such as the PI3K-Akt signaling pathway, Jak-STAT signaling pathway, and mTOR signaling pathway. ChIP-seq analysis indicated that histone lactylation modification in the promoter regions of the GDM group was significantly changed. By integrating the results of RNA-seq and ChIP-seq analysis, we found that CACNA2D1 is a key gene for histone lactylation modification and is involved in the progression of GDM by promoting cell vitality and proliferation. In conclusion, we identified the key gene CACNA2D1, which upregulated and exhibited hypermodification of histone lactylation in GDM. These findings establish a theoretical groundwork for the targeted therapy of GDM.

The role of aspirin dose and initiation time in the prevention of preeclampsia and corresponding complications: a meta-analysis of RCTs.

PURPOSE: To investigate the role of different dosages and initial times of aspirin in preeclampsia prevention. METHODS: This meta-analysis was performed based on randomized-control trials (RCTs). RCTs of women assigned to receive low-dose aspirin, placebo, or no treatment were included. Preeclampsia and corresponding complications were pooled for analysis. All studies were retrieved from PubMed, Embase, Cochrane and Web of Science. RESULTS: A total of 46 studies were obtained in this meta-analysis, which consisted of 24,028 participants. When women at ≤ 16 gestational weeks started treatment with a dosage of < 100 mg/day aspirin, there was a significant reduction in the incidence of preeclampsia (RR = 0.75; 95% CI 0.58-0.98; P = 0.03), while in the subgroup receiving ≥ 100 mg/day aspirin, the result was RR = 0.71 (95% CI 0.53-0.95; P = 0.02). When aspirin was initiated at > 16 weeks, with a dosage of < 100 mg/day aspirin, there was a lesser preventive effect (RR = 0.80; 95% Cl 0.64-1.00; P = 0.05), and there was no significance in the subgroup receiving ≥ 100 mg/day aspirin (RR = 0.76; 95% Cl 0.45-1.31; P = 0.32). Furthermore, aspirin was revealed to have a protective effect on reducing preterm delivery, but there was an increased risk of postpartum hemorrhage. No significant result was obtained for fetal loss. CONCLUSION: The results of this meta-analysis suggest that high-risk pregnant women can prevent preeclampsia or preterm delivery by taking low-dose aspirin; the most efficient period is ≤ 16 weeks of gestation, and the best dose is ≥ 100 mg.

Prostaglandin E2 promotes BeWo spheroids implantation in RL95-2 cell monolayers.

PURPOSE: Integrin αvß3 (ITG αvß3) participates in the process of implantation between the embryo and the endometrium. This study investigated the effects of prostaglandin E2 (PGE2) on endometrial receptivity and implantation efficiency of the embryo, and their possible mechanisms. METHODS: Quantitative real-time reverse transcription PCR (qRT-PCR) and western blotting were used to detect the changes in mRNA and protein levels of ITG αvß3 in RL95-2 cells after administering PGE2. BeWo trophoblast cells and RL95-2 endometrial epithelial cells were used to establish an in vitro model, which was used to observe the adhesion rate and spreading efficiency between BeWo spheroids and RL95-2 cell monolayers after pretreatment with different concentrations of PGE2. RESULTS: PGE2 at 200 nM increased the mRNA and protein levels of ITG αv significantly (p < 0.05); 100 nM PGE2 increased the mRNA and protein levels of ITG ß3 significantly (p < 0.05). PGE2 at 200 nM increased significantly the adhesion and spreading efficiency of BeWo spheres to RL95-2 cell monolayers. CONCLUSIONS: An appropriate concentration of PGE2 might increase the expression of ITG αvß3, which would, promote embryo adhesion and spreading efficiency. This study provides further evidence that increased expression of ITG αvß3 might promote implantation by improving endometrial receptivity.

Efficacy evaluation of low-dose aspirin in IVF/ICSI patients evidence from 13 RCTs: A systematic review and meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis of existing literature to evaluate the different outcomes of low-dose aspirin on patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), including clinical pregnancy rate, implantation rate, live birth rate, miscarriage rate, fertilization rate, number of oocytes retrieved, and so forth. METHODS: Electronic databases including PubMed, MEDLINE, and Embase were searched between 1997 and March 2016 to identity eligible studies. The following comparisons between treatment groups were included: aspirin versus placebo; aspirin versus control group; aspirin versus aspirin + prednisolone + control. RESULTS: Thirteen randomized controlled trials which included 3104 participants were selected. There were no significant differences in implantation rate (RR = 1.15; 95% CI = 0.78-1.70), live birth rate (RR = 1.06; 95% CI = 0.93-1.21), miscarriage rate (RR = 1.28; 95% CI = 0.93-1.77), fertilization rate (RR = 0.91; 95% CI = 0.75-1.11), and endometrial thickness (WMD = 0.15; 95% CI = -0.38-0.67). But the research showed that aspirin treatment may improve the clinical pregnancy rate (RR = 1.16; 95% CI = 1.04-1.28) compared to placebo or no treatment, and reduce the number of oocytes retrieved (WMD = -0.68; 95% CI = -0.91-0.46). CONCLUSIONS: Our findings suggest that low-dose aspirin may improve the pregnancy rate in IVF/ICSI, with the recommended clinical use dose of 100 mg/day. Considering the limitation of included studies, further well-designed large-scaled RCTs are necessary to clarify whether aspirin may improve assisted reproduction outcomes in IVF/ICSI patients.

The influence of different growth hormone addition protocols to poor ovarian responders on clinical outcomes in controlled ovary stimulation cycles: A systematic review and meta-analysis.

BACKGROUND: Growth hormone (GH) is used as an adjuvant therapy in in vitro fertilization and embryo transfer (IVF-ET) for poor ovarian responders, but findings for its effects on outcomes of IVF have been conflicting. The aim of the study was to compare IVF-ET outcomes among women with poor ovarian responders, and find which subgroup can benefit from the GH addition. METHODS: We searched the databases, using the terms "growth hormone," "GH," "IVF," "in vitro fertilization." Randomized controlled trials (RCT) were included if they assessed pregnancy rate, live birth rate, collected oocytes, fertilization rate, and implantation rate. Extracted the data from the corresponding articles, Mantel-Haenszel random-effects model, or fixed-effects model was used. Eleven studies were included. RESULTS: Clinical pregnancy rate (RR 1.65, 95% CI 1.23-2.22), live birth rate (RR1.73, 1.25-2.40), collected oocytes number (SMD 1.09, 95% CI 0.54-1.64), MII oocytes number (SMD 1.48, 0.84-2.13), and E2 on human chorionic gonadotropin (HCG) day (SMD 1.03, 0.18-1.89) were significantly increased in the GH group. The cancelled cycles rate (RR 0.65, 0.45-0.94) and the dose of gonadotropin (Gn) (SMD -0.83, -1.47, -0.19) were significantly lower in patients who received GH. Subgroup analysis indicated that the GH addition with Gn significantly increased the clinical pregnancy rate (RR 1.76, 1.25-2.48) and the live birth rate (RR 1.91, 1.29-2.83). CONCLUSION: The GH addition can significantly improve the clinical pregnancy rate and live birth rate. Furthermore, the GH addition time and collocation of medications may affect the pregnancy outcome.

A systematic review and meta-analysis of metformin among patients with polycystic ovary syndrome undergoing assisted reproductive technology procedures.

BACKGROUND: Metformin is used among patients with polycystic ovary syndrome (PCOS), but findings for its effects on outcomes of assisted reproductive technology (ART) have been conflicting. OBJECTIVES: To compare ART outcomes among women with PCOS who were and were not given metformin. SEARCH STRATEGY: Databases were searched for reports published in English between 2002 and 2013, using combinations of the terms "polycystic ovary syndrome," "PCOS," "insulin-sensitizing," and "metformin." SELECTION CRITERIA: Randomized controlled trials of metformin versus placebo among women with PCOS undergoing ART were included if they assessed rates of pregnancy, live birth, spontaneous abortion, multiple pregnancy, and/or ovarian hyperstimulation syndrome (OHSS). DATA COLLECTION AND ANALYSIS: Data were extracted from included studies. The Mantel-Haenzel random-effects model was used for meta-analyses. MAIN RESULTS: Twelve studies (1516 participants) were included. No significant differences were recorded between metformin and placebo groups for rates of pregnancy (risk ratio [RR] 1.11, 95% CI 0.92-1.33), live birth (RR 1.12, 0.92-1.36), spontaneous abortion (RR 1.00, 0.60-1.67), or multiple pregnancy (RR 0.96, 0.47-1.96). However, OHSS rate was significantly lower among patients who received metformin than among those who received placebo (RR 0.44, 0.26-0.77). CONCLUSIONS: Metformin does not improve ART outcomes among patients with PCOS, but does significantly reduce their risk of OHSS.

Estrogen supplementation to progesterone as luteal phase support in patients undergoing in vitro fertilization: systematic review and meta-analysis.

Meta-analyses have found conflicting results with respect to the use of progesterone or progesterone plus estrogen as luteal phase support for in vitro fertilization (IVF) protocols involving gonadotropins and/or gonadotropin-releasing hormone analogs. The aim of the present study was to perform an updated meta-analysis on the efficacy of progesterone versus progesterone plus estrogen as luteal phase support. We searched the MEDLINE, Cochrane Library, and Google Scholar databases (up to March 18, 2014). The search terms were (estrogen OR estradiol OR oestradiol) AND (progesterone) AND (IVF OR in vitro fertilization) AND (randomized OR prospective). We did not limit the form of estrogen and included subjects who contributed more than 1 cycle to a study. The primary outcome was clinical pregnancy rate. Secondary outcomes were ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate. A total of 11 articles were included in the present analysis, with variable numbers of studies assessing each outcome measure. Results of statistical analyses indicated that progesterone plus estrogen treatment was more likely to result in clinical pregnancy than progesterone alone (pooled odds ratio 1.617, 95% confidence interval 1.059-2.471; P = 0.026). No significant difference between the 2 treatment regimens was found for the other outcome measures. Progesterone plus estrogen for luteal phase support is associated with a higher clinical pregnancy rate than progesterone alone in women undergoing IVF, but other outcomes such as ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate are the same for both treatments.