Membrane integrity is essential in maintaining sperm viability, signaling, and motility, which are essential for fertilization. Sperm are highly susceptible to oxidative stress, as they are rich in sensitive polyunsaturated fatty acids (PUFA), and are unable to synthesize and repair many essential membrane constituents. Because of this, sperm cellular membranes are important targets of this process. Membrane Lipid Replacement (MLR) with glycerophospholipid mixtures (GPL) has been shown to ameliorate oxidative stress in cells, restore their cellular membranes, and prevent loss of function. Therefore, we tested the effects of MLR on sperm by tracking and monitoring GPL incorporation into their membrane systems and studying their effects on sperm motility and viability under different experimental conditions. Incubation of sperm with mixtures of exogenous, unoxidized GPL results in their incorporation into sperm membranes, as shown by the use of fluorescent dyes attached to GPL. The percent overall (total) sperm motility was increased from 52±2.5% to 68±1.34% after adding GPL to the incubation media, and overall sperm motility was recovered from 7±2% after H2O2 treatment to 58±2.5%)(n = 8, p<0.01) by the incorporation of GPL into sperm membranes. When sperm were exposed to H2O2, the mitochondrial inner membrane potential (MIMP), monitored using the MIMP tracker dye JC-1 in flow cytometry, diminished, whereas the addition of GPL prevented the decrease in MIMP. Confocal microscopy with Rhodamine-123 and JC-1 confirmed the mitochondrial localization of the dyes. We conclude that incubation of human sperm with glycerolphospholipids into the membranes of sperm improves sperm viability, motility, and resistance to oxidizing agents like H2O2. This suggests that human sperm might be useful to test innovative new treatments like MLR, since such treatments could improve fertility when it is adversely affected by increased oxidative stress.
During pregnancy, a series of physiological changes are determined at the molecular, cellular and macroscopic level that make the mother and fetus more susceptible to certain viral and bacterial infections, especially the infections in this and the companion review. Particular situations increase susceptibility to infection in neonates. The enhanced susceptibility to certain infections increases the risk of developing particular diseases that can progress to become morbidly severe. For example, during the current pandemic caused by the SARS-CoV-2 virus, epidemiological studies have established that pregnant women with COVID-19 disease are more likely to be hospitalized. However, the risk for intensive care unit admission and mechanical ventilation is not increased compared with nonpregnant women. Although much remains unknown with this particular infection, the elevated risk of progression during pregnancy towards more severe manifestations of COVID-19 disease is not associated with an increased risk of death. In addition, the epidemiological data available in neonates suggest that their risk of acquiring COVID-19 is low compared with infants (<12 months of age). However, they might be at higher risk for progression to severe COVID-19 disease compared with older children. The data on clinical presentation and disease severity among neonates are limited and based on case reports and small case series. It is well documented the importance of the Zika virus infection as the main cause of several congenital anomalies and birth defects such as microcephaly, and also adverse pregnancy outcomes. Mycoplasma infections also increase adverse pregnancy outcomes. This review will focus on the molecular, pathophysiological and biophysical characteristics of the mother/placental-fetal/neonatal interactions and the possible mechanisms of these pathogens (SARS-CoV-2, ZIKV, and Mycoplasmas) for promoting disease at this level.
Lead is a heavy metal pollutant that constitutes frequent exposomes. It is nonbiodegradable and has a nonsafe limit of exposure. It has multisystemic effects, and most of the cardiac effects have been discovered to be indirect. There are strong similarities between Ca2+ and Pb2+ in their chemistry. Because cardiac function is dramatically dependent in extracellular Ca2+, as well as in precise control of intracellular Ca2+, we tested if Pb2+ could antagonize Ca2+-dependent effects in a short amount of time. Acute exposure of isolated hearts showed a negative inotropic effect. In guinea pig isolated cardiomyocytes loaded with a Pb2+-specific dye (Leadmium green), our results showed that there was an associated increment in fluorescence related to extracellular stimulation blocked by 1–5 µM DHP. Calcium currents were partially blocked by extracellular Pb2+, though currents seemed to last longer after a fast inactivation. Charge movement from gating currents was slightly hastened over time, giving an appearance of a slight reduction in the Cav1.2 gating currents. Action potentials were prolonged in Pb2+ compared with Ca2+. In isolated cardiomyocytes loaded with Ca2+-sensitive dyes, Ca2+ variations promoted by extracellular stimuli were affected in space/time. As Pb2+ could interfere with Ca2+-sensitive dyes, we measured contraction of isolated cardiomyocytes under extracellular stimuli in Pb2+. In both Ca2+ dye fluorescence and contractions, Pb2+ disorganizes the pattern of contraction and intracellular Ca2+ homeostasis. Our results suggest that (1) Pb2+ enters to cardiomyocytes through Cav1.2 channels, and (2) once it enters the cell, Pb2+ may substitute Ca2+ in Ca2+-binding proteins. In addition to these direct mechanisms related to Pb2+ competition with Ca2+-binding sites, we cannot discard a direct contribution of Pb2+ redox properties.
Cancer and cardiovascular diseases are the main causes of death in Uruguay and developed countries. In clinical practice, there is often the need to administrate chemotherapy with cisplatin (CTP) to patients with cardiovascular comorbidities. The aim of this work is to characterize the possible detrimental effects in cardiac function by the acute exposition to CPT using isolated heart and cardiomyocytes from guinea pigs (Cavia porcellus). All the procedures regarding animal experimentation were performed following approved protocols by the university ethics committee. Isolated hearts were placed in a Langendorff system and perfused with Tyrode 1.8 mM Ca2+ as control medium, or with extracellularly added CPT (0–100 µM). Tension was recorded with a gauge force transducer attached to the papillary muscle and electrical responses were measured with Ag-AgCl electrodes placed in surface extremes near the papillary muscle. Cardiomyocytes were isolated by enzymatic methods. Data were obtained by patch clamp and confocal microscopy with Rhodamine and Fluo dyes sensitive to Ca2+ binding. Non-parametric t tests were used for data comparison. The best fit of Hill’s equation to dose–response curves was done using nonlinear regression methods. In isolated hearts, CPT showed a biphasic effect over the development of tension, increasing up to 5–10 µM to decrease at higher concentrations. In isolated cardiomyocytes, Ca2+ currents were stimulated and inhibited by CPT in a similar dose. Confocal microscopy showed an increment and a reduction of relative fluorescence of the calcium-sensitive dyes with CPT as well. Our results suggest that CPT may affect cardiac contraction and automatism upon acute exposure of the heart, presumably by blocking L-type (Cav1.2) calcium channels and interference with molecules involved in maintaining the homeostasis of intracellular Ca2+.
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