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The extracellular vesicles (EVs) in uterine fluids play a vital role in embryo implantation by mediating intrauterine communication between conceptus and maternal endometrium in pigs. However, the regulatory mechanism of EVs in uterine fluids is largely unclear. In order to understand the effect of EVs in uterine flushing fluids (UFs) during embryo implantation on endometrial epithelial cells (EECs) and embryonic trophoblast cells (PTr2 cells). The UFs-EVs on day 13 of pregnancy (D13) were added to the culture medium of EECs and PTr2 cells. It was found that PKH-67 labeled UFs-EVs could be taken up in EECs and PTr2 cells. Transcriptome sequencing analysis showed that a total of 1793 and 6279 genes were differentially expressed in the EECs and PTr2 cells after the treatment of UFs-EVs on D13, respectively. Among these genes, real-time quantitative PCR (RT-qPCR) results indicated that ID2, ITGA5, CXCL10 and CXCL11 genes were differentially expressed in both EECs and PTr2 cells after treatment. Bioinformatics analysis showed that the differentially expressed (DE) genes in EECs and PTr2 cells after treatment are involved in immune regulation, cell migration, cell adhesion and the secretion and uptake of EVs. Our research offers novel insight into the regulation mechanism of UFs-EVs on D13 in EECs and PTr2 cells.

Endometrial receptivity plays a vital role in successful embryo implantation in pigs. MicroRNAs (miRNAs), known as regulators of gene expression, have been implicated in the regulation of embryo implantation. However, the role of miRNAs in endometrial receptivity during the pre-implantation period remains elusive. In this study, we report that the expression level of Sus scrofa (ssc)-miR-21-5p in porcine endometrium tissues was significantly increased from day 9 to day 12 of pregnancy. Knockdown of ssc-miR-21-5p inhibited proliferation and migration of endometrial epithelial cells (EECs), and induced their apoptosis. We verified that programmed cell death 4 (PDCD4) was a target gene of ssc-miR-21-5p. Inhibition of PDCD4 rescued the effect of ssc-miR-21-5p repression on EECs. Our results also revealed that knockdown of ssc-miR-21-5p impeded the phosphorylation of AKT (herein referring to AKT1) by targeting PDCD4, which further upregulated the expression of Bax, and downregulated the levels of Bcl2 and Mmp9. Furthermore, loss of function of Mus musculus (mmu)-miR-21-5p in vivo resulted in a decreased number of implanted mouse embryos. Taken together, knockdown of ssc-miR-21-5p hampers endometrial receptivity by modulating the PDCD4/AKT pathway.

Serum 1,5-anhydro-d-glucitol (1,5-AG) concentrations are short-term hyperglycemia indicators and were used to estimate the effects of serum vitamin D concentrations on glycemic control in patients with type 2 diabetes mellitus (T2DM). Serum concentrations of 1,5-AG, 25-hydroxyvitamin D2(25-OH-D2), and 25-hydroxyvitamin D3(25-OH-D3) from 11 026 patients with T2DM, hospitalized in the Department of Endocrinology, Shanghai Central Hospital of Xuhui District, from January 2012 to June 2015, were retrospectively analyzed. Correlation analyses revealed correlations between 1,5-AG and 25-OH-D3(r = 0.05, P < 0.001), age (r = 0.05, P < 0.001), and 25-OH-D2+ 25-OH-D3(25-OH-D2/D3) (r = 0.05, P < 0.001). Linear regression analyses revealed associations between 1,5-AG and 25-OH-D2/D3(adjusted R2= 0.003) as well as 25-OH-D3(adjusted R2= 0.002). In males with 1,5-AG levels ≤11.55 mg/L, serum concentrations of 25-OH-D2(P < 0.001) and 25-OH-D3(P = 0.001) were significantly lower than those in diabetic males with 1,5-AG levels >11.55 mg/L. Serum concentrations of 25-OH-D2/D3in patients with T2DM were associated with 1,5-AG retention, suggesting involvement in glycemic control.

Retinol-binding protein 4 (RBP4) is thought to be associated with insulin resistance in humans, while pregnancy is normally characterized by progressive insulin resistance. Gestational diabetes (GDM) occurs when pancreatic beta-cell function is unable to compensate for insulin resistance. This study aimed to determine whether or not serum RBP4 levels are elevated in pregnancy, and to explore the relationship between RBP4 levels and insulin resistance during pregnancy.Serum RBP4 was measured at median gestational week 26 in 121 pregnant women, including 63 with GDM (GDM group) and 58 normal, glucose-tolerant pregnant women (P-NGT group), as well as 65 non-pregnant normal, glucose-tolerant women (NP-NGT group). Multiple stepwise regression analysis was used to explore the independent factors of RBP4.Serum RBP4 levels in the P-NGT and GDM groups were significantly higher than in the NP-NGT group (34.50±9.80 mg/L and 41.64±12.21 mg/L vs 30.64±9.46 mg/L, respectively; P0.05) after adjusting for age, body mass index (BMI) and blood pressure. Furthermore, RBP4 levels were much higher in the GDM vs P-NGT group. Spearman's correlation analysis showed that serum RBP4 levels were positively correlated with triglycerides (TG), fasting plasma glucose, postprandial 2h plasma glucose and HOMA-IR in pregnancy. Of these, TG and HOMA-IR (r(2)=0.312) were independent factors of serum RBP4.Serum RBP4 levels are significantly increased in pregnancy, independent of age and BMI, and are also considerably higher in pregnant women with GDM than in those with normal glucose tolerance. In addition, serum RBP4 levels appear to be a valuable marker of insulin resistance and dysfunctional lipid metabolism in pregnancy.

TAAAAn polymorphism in sex hormone-binding globulin (SHBG) gene has been found to influence the transcriptional activity of SHBG gene in vitro, and several studies have reported variable associations of this polymorphism with serum SHBG levels in women with polycystic ovary syndrome (PCOS). We have investigated the association of TAAAAn polymorphism with PCOS in 187 women with PCOS and 176 controls; in which five alleles (6-10 repeats) and 13 genotypes were found. None of the TAAAAn alleles or genotypes occurred in significant different frequency in PCOS patients compared with controls. Serum SHBG in the PCOS group was significantly lower than those in controls (33.8 +/- 30.2 nmol/l vs. 65.58 +/- 31.12 nmol/l; P0.01). Serum SHBG concentrations were similar for patients with PCOS whether they displayed short or long genotypes for TAAAAn (Log10SHBG: 1.46 +/- 0.38 and 1.58 +/- 0.33, respectively). Similar results were observed for controls (Log10SHBG: 1.79 +/- 0.17 and 1.77 +/- 0.14, respectively). In contrast, serum SHBG values were negatively associated with body mass index (BMI) and homeostasis model assessment of insulin resistance in the PCOS group (B = -0.285 and -0.264, respectively; P0.01). Thus, the TAAAAn polymorphism in SHBG gene was not a determinant of PCOS in this population of Chinese women, whereas, serum SHBG was significantly associated with BMI and insulin resistance in these PCOS patients.

Variations in the fat mass and obesity-associated (FTO) gene have recently been associated with obesity and type 2 diabetes mellitus among different ethnic populations. Given that the phenotype of polycystic ovary syndrome (PCOS) overlaps with obesity and type 2 diabetes, we hypothesize that the common rs9939609 variant of FTO gene is related to PCOS susceptibility. We performed a case–control association study on 215 women with PCOS, using 227 healthy women as the control. We examined the association between rs9939609 variant and PCOS susceptibility, as well as between PCOS and obesity-related parameters in Chinese women. We observed significant differences in the allelic and genotypic distributions between PCOS patients and the control group. The A allele was significantly more frequent among PCOS patients than in the control population (15.1% vs. 9.9%; A allele vs. T allele, OR = 1.62, P = 0.019). The A allele carrier genotype (AA and AT) frequencies were also significantly greater in PCOS patients than in the controls (28% vs. 19%; AT and TT vs. TT genotype, OR = 1·61, P = 0.035). In logistic regression, the strength of this association was attenuated after adjustment for body mass index (BMI) (A allele vs. T allele, OR = 1.39, P = 0.286; AT and TT genotypes vs. TT genotype, OR = 1.40, P = 0.312). However, we did not find any significant associations of rs9939609 variant with obesity-related traits. In conclusions, the rs9939609 variant in the FTO gene is associated with PCOS susceptibility in the Chinese population, probably because of its effect on BMI.

Hereditary fructose intolerance (HFI) is an inheritable disorder of fructose metabolism, inherited as an autosomal recessive disorder and caused by catalytic deficiency of aldolase B, which is critical for gluconeogenesis and fructose metabolism. The affected individuals develop severe hypoglycemia after taking foods containing fructose and cognate sugars. The exons 2–9 of the aldolase B (gene symbol ALDOB) gene from one Chinese HFI patient were amplified by the polymerase chain reaction (PCR), and direct sequence determination was applied to the amplified fragments. The mutation of a 4-bp (AACA) deletion (479_482 del) in exon 4 of ALDOB gene was identified in the patient, which had been reported to cause a frameshift at codon 118 and a truncated protein of 132 amino acids in the previous study. Then, the second case with the same homozygote deletion and eight cases with heterozygotes had been found through screening for the mutation c.479_482 del AACA in the whole family. This is the first report of HFI with the mutation c.479_482 del AACA in the ALDOB gene in a Chinese family.