Aberrations in the progesterone pathway and the Th1/Th2 cytokine dichotomy - An evaluation of RPL predisposition in the northeast Indian population.

PROBLEM: Recurrent pregnancy loss (RPL) is the spontaneous loss of two or more consecutive pregnancies prior to 20 weeks of gestation, occurring in 1% of the reproductive-age population. It is a major cause of infertility in India with a staggering 7.46% prevalence rate. METHOD OF STUDY: Blood and product of conception (POCs) from RPL cases (n = 65) were enrolled for this study, along with cases of medically terminated pregnancy (MTP, n = 80) and term delivery cases (n = 90) as control. ELISA for progesterone and progesterone induced blocking factor (PIBF) levels was carried out, followed by mRNA expression analysis of progesterone receptor isoform B (PR-B) and its downstream immunomodulatory effectors, namely, PIBF, IL-10 and IL-12. Screening of PROGINS haplotype of PR gene and PIBF polymorphism were also conducted to correlate with their respective gene expression profiles. RESULTS: Serum progesterone level was found to be comparable in the RPL and MTP cases. Although the mRNA expression of PR-B was found to be downregulated in the RPL cases, no significant PROGINS haplotype was observed. Presence of a single nucleotide polymorphism (SNP) in the PIBF gene (rs1372000) was more in healthy controls compared to RPL cases. Serum PIBF levels were found to be lower in the RPL cases with a resultant increase in IL-12 and a decrease in IL-10 mRNA expression in these cases. CONCLUSIONS: This study indicates that progesterone, acting through PIBF, modulates the immunological state of pregnancy to be Th1-biased in RPL, indicative of a pro-inflammatory, labour-like state not desired for a healthy pregnancy.

Effect of two monoterpene phenols on antioxidant defense system in Candida albicans.

Thymol and carvacrol from the class of monoterpene phenols are one of the most potent plant essential oil components possessing antimicrobial effects. Known for their wide bioactive spectrum, these positional isomers of isopropyl cresol deplete ergosterol content, compromise membrane permeability, block efflux pumps and restore antifungal susceptibility to fluconazole in resistant Candida strains. Exposure to these natural compounds induces a cascade of stress responses, which are important to comprehend their microbicidal mechanisms. This study evaluates the antioxidant defense response to lower concentrations of thymol and carvacrol in Candida albicans. The antioxidant defense responses in C. albicans are important for developmental mechanisms pertaining to resistance against the immune system, infection establishment and drug resistance. In this view, primary and secondary antioxidant defense enzymes, and oxidative stress markers including glutathione and lipid peroxidation were determined in C. albicans cells exposed to lower concentrations of thymol and carvacrol. These compounds were found to induce oxidative stress and compromised the antioxidant defense system in C. albicans at lower concentrations. This study helps in understanding the 'in cell' antifungal mechanisms of natural monoterpene phenols originating from oxidative stress. Thymol and carvacrol induced membrane deterioration reported earlier, is further explained as a result of a toxic radical cascade mediated by lipid peroxidation. Findings reinforce the observed toxic oxidizing effects of these compounds as a consequence of direct damage to antioxidant components and not to their genetic manipulations.