Evidence has demonstrated iron accumulation in specific brain regions of patients suffering from neurodegenerative disorders, and this metal has been recognized as a contributing factor for neurodegeneration. Using an experimental model of brain iron accumulation, we have shown that iron induces severe memory deficits that are accompanied by oxidative stress, increased apoptotic markers, and decreased synaptophysin in the hippocampus of rats. The present study aims to characterize iron loading effects as well as to determine the molecular targets of cannabidiol (CBD), the main non-psychomimetic compound of Cannabis sativa, on mitochondria. Rats received iron in the neonatal period and CBD for 14 days in adulthood. Iron induced mitochondrial DNA (mtDNA) deletions, decreased epigenetic modulation of mtDNA, mitochondrial ferritin levels, and succinate dehydrogenase activity. CBD rescued mitochondrial ferritin and epigenetic modulation of mtDNA, and restored succinate dehydrogenase activity in iron-treated rats. These findings provide new insights into molecular targets of iron neurotoxicity and give support for the use of CBD as a disease modifying agent in the treatment of neurodegenerative diseases.
Brain-derived neurotrophic factor (BDNF) plays a key role in neural development and physiology, as well as in pathological states. Post-mortem studies demonstrate that BDNF is reduced in the brains of patients affected by neurodegenerative diseases. Iron accumulation has also been associated to the pathogenesis of neurodegenerative diseases. In rats, iron overload induces persistent memory deficits, increases oxidative stress and apoptotic markers, and decreases the expression of the synaptic marker, synaptophysin. Deferiprone (DFP) is an oral iron chelator used for the treatment of systemic iron overload disorders, and has recently been tested for Parkinson's disease. Here, we investigated the effects of iron overload on BDNF levels and on mRNA expression of genes encoding TrkB, p75, catalase (CAT) and NQO1. We also aimed at investigating the effects of DFP on iron-induced impairments. Rats received iron or vehicle at postnatal days 12-14 and when adults, received chronic DFP or water (vehicle). Recognition memory was tested 19 days after the beginning of chelation therapy. BDNF measurements and expression analyses in the hippocampus were performed 24 h after the last day of DFP treatment. DFP restored memory and increased hippocampal BDNF levels, ameliorating iron-induced effects. Iron overload in the neonatal period reduced, while treatment with DFP was able to rescue, the expression of antioxidant enzymes CAT and NQO1.
Partial results of this paper were presented as an oral communication during ESHRE virtual 36 th Annual Meeting.
Background In spontaneous pregnancies, maternal weight and gestational diabetes are independent risk factors for macrosomia and large-for-gestational-age newborns. Furthermore, maternal body mass index (BMI) of ≥25 kg/m2 is associated with worse neonatal vitality, classified as an Apgar score of < 7 at the fifth minute of life. However, few studies have evaluated the influence of BMI on perinatal outcomes in pregnancies resulting from assisted reproduction. Therefore, this study aimed to analyze whether the perinatal outcomes of assisted reproduction are influenced by BMI. Methods This was a retrospective cohort study performed at a reproductive medicine center. Patients undergoing assisted reproduction (2013–2020) were divided into three groups according to their BMI (kg/m2): group 1, < 25; group 2, 25–29.9, and group 3, ≥30. In total, 1753 in vitro fertilization embryo transfer cycles were analyzed. Data were expressed as mean ± standard deviation or frequency (%). The analysis of variance and chi-square test were performed for comparison. To determine the participants and number of cycles for these analyses, generalized estimating equations were used, considering p < 0.05. Results In groups 1, 2, and 3, the rates of live birth were 33.5, 32.3, and 29.9% (p = 0.668); preeclampsia were 2.9, 6.1, and 6.3% (p = 0.268); small-for-gestational-age newborns were 23, 23.2, and 21.7% (p = 0.965); macrosomia were 1.9, 0.9, and 2.7% (p = 0.708); Apgar score > 7 at the fifth minute were 97.6, 98.2, and 100% (p = 0.616); and preterm birth were 29.6, 30.1, and 35.1% (p = 0.970), respectively. Conclusions In conclusion, although the three groups had similar perinatal outcomes in this study, the study population was too small for conclusive results. The higher the BMI, the lower the chances of clinically relevant LBR and the higher the chances of premature labor and preeclampsia.
Background The aim of this study was to evaluate the influence of the body mass index (BMI) on laboratory, clinical outcomes and treatment costs of assisted reproduction, as there are still controversial and inconclusive studies on this subject. Methods This research was retrospective cohort study, including women undergoing assisted reproduction in a Reproductive Medicine Center between 2013 and 2020. The participants were divided into groups according to BMI (kg/m2): Group 1 < 25; Group 2, 25–29.9 and Group 3, ≥ 30. A total of 1753 in vitro fertilization (IVF) fresh embryo transfer (ET) cycles were included for assisted reproduction outcomes analysis and 1869 IVF-ET plus frozen embryo transfer (FET) for cumulative pregnancy analysis. Results As higher the BMI, higher was the proportion of canceled IVF cycles (G1 (6.9%) vs. G2 (7.8%) vs. G3 (10.4%), p = 0.002) and gonadotropin’s total dose (IU) and treatment costs (G1 (1685 ± 595, U$ 683,02) vs. G2 (1779 ± 610, U$ 721,13) vs. G3 (1805 ± 563, U$ 764,09), p = 0.001). A greater number of mature oocytes was observed in G1 and G2 (6 [6.4–7.0] vs. 6 [5.6–6.6] vs. 4 [4.6–6.7], p = 0.011), which was not found in oocyte maturity rate (p = 0.877). A significant linear tendency (p = 0.042) was found in cumulative pregnancy rates, pointing to worse clinical outcomes in overweight and obese patients. Conclusion These findings highlight the importance of considering the higher treatment costs for these patients, beyond all the well-known risks regarding weight excess, fertility, and pregnancy, before starting IVF treatments.
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