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While ultraviolet C (UVC) radiation has beneficial applications, it can also pose risks to living organisms. Nevertheless, a detailed assessment of UVC radiation's effects on mammalian male reproductive physiology, including the underlying mechanisms and potential protective strategies, has not yet been accomplished. This study aimed to examine the critical roles of oxidative stress, autophagy, reproductive hormonal axis, and microRNAs in UVC-induced reproductive challenges in male rats. Semen, biochemical, molecular, and in silico analyses revealed significant dysregulation of testicular steroidogenesis, impaired spermatogenesis, deteriorated sperm quality, and altered reproductive hormonal profiles, which ultimately lead to a decline in fertility in male rats exposed to UVC radiation. Our data indicated that the suppression of autophagy, stimulation of gonadotropin-inhibiting hormone (GnIH), and alteration of microRNAs serve as key mediators of UVC-induced stress effects in mammalian reproduction, potentially contributing to male infertility. Targeting these pathways, particularly through pretreatment with hesperidin (HES), offers a promising strategy to counteract UVC-induced male infertility. In conclusion, the present findings emphasize the importance of understanding the molecular mechanisms behind UVC-induced male infertility and offer valuable insights into the protective mechanisms and prospective role of HES in safeguarding male reproductive health. [ABSTRACT FROM AUTHOR]

The central aim of this study was to investigate whether male Wistar rats chronically fed a high-fat diet (HFD) over 106 days present high levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and Na+ and Ca2+ transport alterations in the left ventricle, together with dyslipidemia and decreased glucose tolerance, and to investigate the influence of Ang-(3–4). The rats became moderately overweight with an expansion of visceral adiposity. Na+-transporting ATPases, sarco-endoplasmic reticulum Ca2+-ATPase (SERCA2a), and the abundance of Angiotensin II receptors were studied together with lipid and glycemic profiles from plasma and left-ventricle echocardiographic parameters fractional shortening (FS) and ejection fraction (EF). IL-6 and TNF-α increased (62% and 53%, respectively), but returned to normal levels with Angiotensin-(3–4) administration after 106 days. Significant lipidogram alterations accompanied a decrease in glucose tolerance. Angiotensin II receptors abundance did not change. (Na+ + K+)ATPase and ouabain-resistant Na+-ATPase were downregulated and upregulated, respectively, but returned to normal values upon Angiotensin-(3–4) administration. SERCA2a lost its ability to respond to excess ATP. Echocardiography showed no changes in FS or EF. We conclude that being overweight causes an increase in Ang-(3–4)-sensitive IL-6 and TNF-α levels, and ion transport alterations in the left ventricle that could evolve into future heart dysfunction. [ABSTRACT FROM AUTHOR]

In oviparous marine fishes, the hyperosmotic induction of sperm motility in seawater (SW) is well established, however, the potential function of ion channels in the maintenance of post activated spermatozoon swimming performance remains largely unknown. Here, we investigated the influence of ion channels on the spermatozoon swimming parameters using the gilthead seabream (Sparus aurata) as a model for modern marine teleosts. Our data show that the SW-induced activation of seabream sperm motility requires three concomitant processes, the hyperosmotic shock, an ion-flux independent increase of the intracellular concentration of Ca2+ ([Ca2+]i), but not of [K+]i or [Na+]i, and the alkalization of the cytosol. The combination of all three processes is obligatory to trigger flagellar beating. However, the time-course monitoring of sperm motion kinetics and changes in the [Ca2+]i, [K+]i and [Na+]i in SW or in non-ionic activation media, showed that the post activated maintenance of spermatozoa motility is dependent on extracellular Ca2+ and K+. A meta-analysis of a seabream sperm transcriptome uncovered the expression of multiple ion channels, some of which were immunolocalized in the head and/or tail of the spermatozoon. Selective pharmacological inhibition of these ion channel families impaired the long-term motility, progressivity, and velocity of SW-activated spermatozoa. The data further revealed that some antagonists of K+-selective or Ca2+-selective channels, as well as of stretch-activated and mechanosensitive channels, altered the trajectory of spermatozoa, suggesting that these ion channels are likely involved in the control of the swimming pattern of the post activated spermatozoon. These combined findings provide new insight into the signaling pathways regulating spermatozoon activation and swimming performance in marine fishes. [ABSTRACT FROM AUTHOR]

Alkalinization of sperm cytosol is essential for plasma membrane hyperpolarization, hyperactivation of motility, and acrosomal exocytosis during sperm capacitation in mammals. The plasma membrane of sperm cells contains different ion channels implicated in the increase of internal pH (pHi) by favoring either bicarbonate entrance or proton efflux. Bicarbonate transporters belong to the solute carrier families 4 (SLC4) and 26 (SLC26) and are currently grouped into Na+/HCO3− transporters and Cl−/HCO3− exchangers. Na+/HCO3− transporters are reported to be essential for the initial and fast entrance of HCO3− that triggers sperm capacitation, whereas Cl−/HCO3− exchangers are responsible for the sustained HCO3− entrance which orchestrates the sequence of changes associated with sperm capacitation. Proton efflux is required for the fast alkalinization of capacitated sperm cells and the activation of pH-dependent proteins; according to the species, this transport can be mediated by Na+/H+ exchangers (NHE) belonging to the SLC9 family and/or voltage-gated proton channels (HVCN1). Herein, we discuss the involvement of each of these channels in sperm capacitation and the acrosome reaction. [ABSTRACT FROM AUTHOR]

Human spermatozoan ion channels are specifically distributed in the spermatozoan membrane, contribute to sperm motility, and are associated with male reproductive abnormalities. Calcium, potassium, protons, sodium, and chloride are the main ions that are regulated across this membrane, and their intracellular concentrations are crucial for sperm motility. Fatty acids (FAs) affect sperm quality parameters, reproductive pathologies, male fertility, and regulate ion channel functions in other cells. However, to date the literature is insufficient to draw any conclusions regarding the effects of FAs on human spermatozoan ion channels. Here, we aimed to discern the possible effects of FAs on spermatozoan ion channels and direct guidance for future research. After investigating the effects of FAs on characteristics related to human spermatozoan motility, reproductive pathologies, and the modulation of similar ion channels in other cells by FAs, we extrapolated polyunsaturated FAs (PUFAs) to have the highest potency in modulating sperm ion channels to increase sperm motility. Of the PUFAs, the ω-3 unsaturated fatty acids have the greatest effect. We speculate that saturated and monounsaturated FAs will have little to no effect on sperm ion channel activity, though the possible effects could be opposite to those of the PUFAs, considering the differences between FA structure and behavior. [ABSTRACT FROM AUTHOR]

A randomized prospective clinical study performed on a group of 74 pregnant women (43 presenting with severe preeclampsia) proved that urinary levels of 15-F2t-isoprostane were significantly higher in preeclamptic patients relative to the control (3.05 vs. 2.00 ng/mg creatinine). Surprisingly enough, plasma levels of 25-hydroxyvitamin D3 in both study groups were below the clinical reference range with no significant difference between the groups. In vitro study performed on isolated placental mitochondria and placental cell line showed that suicidal self-oxidation of cytochrome P450scc may lead to structural disintegration of heme, potentially contributing to enhancement of oxidative stress phenomena in the course of preeclampsia. As placental cytochrome P450scc pleiotropic activity is implicated in the metabolism of free radical mediated arachidonic acid derivatives as well as multiple Vitamin D3 hydroxylations and progesterone synthesis, we propose that Vitamin D3 might act as a competitive inhibitor of placental cytochrome P450scc preventing the production of lipid peroxides or excess progesterone synthesis, both of which may contribute to the etiopathogenesis of preeclampsia. The proposed molecular mechanism is in accord with the preliminary clinical observations on the surprisingly high efficacy of high-dose Vitamin D3 supplementation in prevention and treatment of preeclampsia. [ABSTRACT FROM AUTHOR]

H+/K+ ATPase Type 2 is an heteromeric membrane protein involved in cation transmembrane transport and consists of two subunits: a specific α subunit (ATP12A) and a non-specific β subunit. The aim of this study was to demonstrate the presence and establish the localization of ATP12A in spermatozoa from Bubalus bubalis, Bos taurus and Ovis aries. Immunoblotting revealed, in all three species, a major band (100 kDa) corresponding to the expected molecular mass. The ATP12A immunolocalization pattern showed, consistently in the three species, a strong signal at the acrosome. These results, described here for the first time in spermatozoa, are consistent with those observed for the β1 subunit of Na+/K+ ATPase, suggesting that the latter may assemble with the α subunit to produce a functional ATP12A dimer in sperm cells. The above scenario appeared to be nicely supported by 3D comparative modeling and interaction energy calculations. The expression of ATP12A during different stages of bovine sperm maturation progressively increased, moving from epididymis to deferent ducts. Based on overall results, we hypothesize that ATP12A may play a role in acrosome reactions. Further studies will be required in order to address the functional role of this target protein in sperm physiology. [ABSTRACT FROM AUTHOR]

Significant antibacterial properties of non-thermal plasma (NTP) have converted this technology into a promising alternative to the widespread use of antibiotics in assisted reproduction. As substantial data available on the specific in vitro effects of NTP on male reproductive cells are currently missing, this study was designed to investigate selected quality parameters of human spermatozoa (n = 51) exposed to diffuse coplanar surface barrier discharge NTP for 0 s, 15 s, 30 s, 60 s and 90 s. Sperm motility characteristics, membrane integrity, mitochondrial activity, production of reactive oxygen species (ROS), DNA fragmentation and lipid peroxidation (LPO) were investigated immediately following exposure to NTP and 2 h post-NTP treatment. Exposure to NTP with a power input of 40 W for 15 s or 30 s was found to have no negative effects on the sperm structure or function. However, a prolonged NTP treatment impaired all the sperm quality markers in a time- and dose-dependent manner. The most likely mechanism of action of high NTP doses may be connected to ROS overproduction, leading to plasma membrane destabilization, LPO, mitochondrial failure and a subsequent loss of motility as well as DNA integrity. As such, our findings indicate that appropriate plasma exposure conditions need to be carefully selected in order to preserve the sperm vitality, should NTP be used in the practical management of bacteriospermia in the future. [ABSTRACT FROM AUTHOR]