Perfluorohexane sulfonate (PFHxS) disturbs the estrous cycle, ovulation rate, oocyte cell communication and calcium homeostasis in mice.

Perfluoroalkyl substances are man-made chemicals with ample consumer and industrial applications. They are widely used and are resistant to environmental and metabolic degradation. Several studies have evaluated the effects of Perfluorohexane sulfonate on reproduction. However, there are few reports exploring the cell and molecular mechanisms of its toxicity in the ovary. The aim of this study was to investigate the effects of PFHxS exposure on the estrous cycle, ovulation rate, and the underlying mechanisms of action in female mice in vivo. The animals received a single sub-lethal dose of PFHxS (25.1 mg/kg, 62.5 mg/kg) or vehicle and were stimulated to obtain immature cumulus cell-oocyte complexes (COCs) from the ovaries, or superovulated to develop mature COCs. To evaluate oocyte physiology, Gap-junction intercellular communication (GJIC) was analyzed in immature COCs and calcium homeostasis was evaluated in mature oocytes. PFHxS exposure prolonged the estrous cycle and decreased ovulation rate in female mice. Connexins, Cx43 and Cx37, were downregulated and GJIC was impaired in immature COCs, providing a possible mechanism for the alterations in the estrous cycle and ovulation. No morphological abnormalities were observed in the mature PFHxS-exposed oocytes, but calcium homeostasis was affected. This effect is probably due, at least partially, to deregulation of the endoplasmic reticulum calcium modulator, Stim1. These mechanisms of ovarian injury could explain the reported correlation among PFHxS levels and subfertility in women undergoing fertility treatments.

Effects of perfluorooctanoic acid in oxidative stress generation, DNA damage in cumulus cells, and its impact on in vitro maturation of porcine oocytes.

Perfluorooctanoic acid is a synthetic compound mostly used in a wide range of consumer products with several adverse effects on somatic cells and gametes. It has been linked to hepatotoxic and carcinogenic effects, alterations in the immune system, endocrine, and reproductive alterations. In vivo studies show an increase in reactive oxygen species and DNA damage. However, the mechanisms by which this compound affects fertility, remain contradictory. Therefore, the aim of the present study was to evaluate the effect of perfluorooctanoic acid on oocyte viability and maturation, as well as the viability, generation of oxidative stress, and genotoxic damage in the cumulus cells exposed during in vitro maturation. This compound had a negative effect on oocyte viability (lethal concentration, LC50  = 269 µM) and maturation (inhibition maturation concentration IM50  = 75 µM), while in cumulus cells the LC50 was 158 µM. The generation of reactive oxygen species evaluated in cumulus cells, protein carbonylation, and DNA damage, was significantly increased at 40 µM perfluorooctanoic acid. This study provides evidence that perfluorooctanoic acid causes reactive oxygen species generation, protein oxidation, and DNA damage in cumulus cells, compromising the maturation and viability of porcine oocyte, which may affect fertility.

Trends of SARS-Cov-2 infection in 67 countries: Role of climate zone, temperature, humidity and curve behavior of cumulative frequency on duplication time

ObjectiveTo analyze the role of temperature, humidity, date of first case diagnosed (DFC) and the behavior of the growth-curve of cumulative frequency (CF) [number of days to rise (DCS) and reach the first 100 cases (D100), and the difference between them ({Delta}DD)] with the doubling time (Td) of Covid-19 cases in 67 countries grouped by climate zone. DesignRetrospective incident case study. SettingWHO based register of cumulative incidence of Covid-19 cases. Participants1,706,914 subjects diagnosed between 12-29-2019 and 4-15-2020. ExposuresSARS-Cov-2 virus, ambient humidity, temperature and climate areas (temperate, tropical/subtropical). Main outcome measuresComparison of DCS, D100, {Delta}DD, DFC, humidity, temperature, Td for the first (Td10) and second (Td20) ten days of the CF growth-curve between countries according to climate zone, and identification of factors involved in Td, as well as predictors of CF using lineal regression models. ResultsTd10 and Td20 were [≥]3 days longer in tropical/subtropical vs. temperate areas (2.8{+/-}1.2 vs. 5.7{+/-}3.4; p=1.41E-05 and 4.6{+/-}1.8 vs. 8.6{+/-}4.2; p=9.7E-05, respectively). The factors involved in Td10 (DFC and {Delta}DD) were different than those in Td20 (Td10 and climate areas). After D100, the fastest growth-curves during the first 10 days, were associated with Td10<2 and Td10<3 in temperate and tropical/subtropical countries, respectively. The fold change Td20/Td10 >2 was associated with earlier flattening of the growth-curve. In multivariate models, Td10, DFC and ambient temperature were negatively related with CF and explained 44.7% (r2 = 0.447) of CF variability at day 20 of the growth-curve, while Td20 and DFC were negatively related with CF and explained 63.8% (r2 = 0.638) of CF variability towards day 30 of the growth-curve. ConclusionsThe larger Td in tropical/subtropical countries is positively related to DFC and temperature. Td and environmental factors explain 64% of CF variability in the best of cases. Therefore, other factors, such as pandemic containment measures, would explain the remaining variability.

Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects.

Chagas disease is a leading cause of heart disease affecting approximately 10 million people in Latin America and elsewhere worldwide. The two major drugs available for the treatment of Chagas disease have limited efficacy in Trypanosoma cruzi-infected adults with indeterminate (patients who have seroconverted but do not yet show signs or symptoms) and determinate (patients who have both seroconverted and have clinical disease) status; they require prolonged treatment courses and are poorly tolerated and expensive. As an alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is under development to prevent or delay Chagasic cardiomyopathy in patients with indeterminate or determinate status. The bivalent vaccine will be comprised of two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy of these antigens was obtained in preclinical testing at the Autonomous University of Yucatan. Here the authors discuss the potential for a therapeutic Chagas vaccine as well as the progress made towards such a vaccine, and the authors articulate a roadmap for the development of the vaccine as planned by the nonprofit Sabin Vaccine Institute Product Development Partnership and Texas Children's Hospital Center for Vaccine Development in collaboration with an international consortium of academic and industrial partners in Mexico, Germany, Japan, and the USA.