Regulation of uterus and placenta remodeling under high estradiol levels in gestational diabetes mellitus models†.

The present study aimed to investigate the regulation of placentas and uterus remodeling and involvement of estradiol in gestational diabetes mellitus. To achieve this, we established in vitro and in vivo models for gestational diabetes mellitus placentas by culturing human placental choriocarcinoma cells (BeWo) under hyperglycemic concentration and treating pregnant rats with streptozotocin. We evaluated the expression of angiogenesis-related proteins. The expression of the anti-angiogenic factor, excess placental soluble fms-like tyrosine kinase 1 was increased in our in vitro gestational diabetes mellitus model compared with the control. Moreover, the expressions of placental soluble fms-like tyrosine kinase 1 and the von Willebrand factor were also significantly elevated in the placenta of streptozotocin-treated rats. These data indicate the disruption of angiogenesis in the gestational diabetes mellitus placentas. The expression levels of connexin 43, a component of the gap junction and collagen type I alpha 2 chain, a component of the extracellular matrix, were decreased in the gestational diabetes mellitus uterus. These results suggest that uterus decidualization and placental angiogenesis are inhibited in gestational diabetes mellitus rats. Our results also showed upregulation of the expression of genes regulating estradiol synthesis as well as estrogen receptors in vivo models. Accordingly, the concentration of estradiol measured in the culture medium under hyperglycemic conditions, as well as in the serum and placenta of the streptozotocin-treated rats, was significantly elevated compared with the control groups. These results suggest that the dysregulated remodeling of the placenta and uterus may result in the elevation of estradiol and its signaling pathway in the gestational diabetes mellitus animal model to maintain pregnancy.

Inhibitory effects and underlying mechanisms of Artemisia capillaris essential oil on melanogenesis in the B16F10 cell line.

The present study investigated the anti­melanogenic activity of 10 essential oils using the B16F10 cell model. Initially, a wide range of concentrations of these essential oils were screened in order to determine their toxicity levels. The assigned non­toxic concentrations of the tested essential oils were then used to evaluate their effects on melanogenesis. The effects of the essential oils with potent anti­melanogenic activity on cell proliferation, protection against H2O2­induced cell death and the expression of certain melanogenesis­related genes, including MITF, tyrosinase, tyrosinase related protein (TRP)­1 and TRP­2 were also evaluated. The results revealed that the essential oils extracted from Citrus unshiu, Juniperus chinensis L., Zanthoxylum piperitum and Artemisia capillaris (A. capillaris) inhibited melanogenesis. However, among these four extracts, only A. capillaris extract enhanced cell proliferation, exhibited anti­H2O2 activities and decreased the expression level of TRP­1. It was demonstrated that A. capillaris extract inhibited melanin synthesis via the downregulation of the TRP­1 translational level. These essential oil extracts, particularly that of A. capillaris, may thus be used as natural anti­melanogenic agents for therapeutic purposes and in the cosmetic industry for skin whitening effects with beneficial proliferative properties. However, further studies using in vivo models are required to validate these findings and to examine the effects of these extracts on various molecular pathways.

Significant association of TNFα and IL-6 gene with male infertility--an explorative study in Indian populations of Uttar Pradesh.

In this study were aimed to identify the association of SNPs candidate genes of TNF-α and IL-6 with hormones levels and sperm cells death in infertile subjects of Uttar Pradesh population in North India. The study population comprised, fertile donor (control group) and infertile group patients i.e. normozoospermic (idiopathic unexplained), oligozoospermic and asthenozoospermic groups, with 260 subjects in each group. Subjects were selected from the Departments of Urology, K.G's Medical University and Urology, SGPGIMS, Lucknow, India. The allele-specific polymerase chain reaction (PCR) and PCR-RFLP were used to investigate the substitution of the guanine (G)-to-adenosine (A) at position-308 and guanine (G)-to-cytosine (C) at position-174 in the promoter regions of the TNF-α and IL-6 genes, respectively. Further their relation to male fertility and sperm function were also investigated. It was found that the substitution levels from G to A and from G to C in the TNF-α and IL-6 genes, respectively, were significantly higher in the infertile subjects as compared to that of control group. The apoptosis and necrosis levels were also higher in oligozoospermic and asthenozoospermic infertile subjects. Further it was found to be associated with increased level of reactive oxygen species as observed in oligozoospermic and asthenozoospermic subjects. However, a significant decrease in testosterone and luteinizing hormone with increased prolactin and follicle stimulating hormones was observed in infertile subjects. The study populations indicating a strong association between TNF-α G-308A and IL-6 G-174C substitution with infertile men which is further supported by allele and genotype meta-analysis and thus established it as a risk factor.