Aquaporin 9 regulates Leydig cell steroidogenesis in diabetes.

Diabetes mellitus induced hyperglycemia increases oxidative stress, which contributes to impairment of male reproductive function. Aquaporins (AQPs) belong to a transmembrane protein superfamily containing 13 isoforms (AQP0-12), differentially expressed in various organs, and play a pivotal role in male reproductive function. In the current study, we investigated the relationship between AQPs and testicular steroidogenesis under hyperglycemia in vivo and in vitro. The effect of high glucose on the role of AQPs in Leydig cell steroidogenesis was analyzed in diabetic rats (in-vivo) and LC540 rat Leydig cells (in vitro) via enzyme assays, quantitative RT-PCR, siRNA knock down and western blotting. AQP 9 was significantly up-regulated in STZ-induced diabetic rat testis and high glucose treated LC540 cells. Further, oxidative stress marker nuclear factor erythroid 2-related factor 2 (Nrf2) expression was decreased with impaired testicular steroidogenesis under hyperglycemia. Knock-down of AQP 9 resulted in increased Nrf2 expression and thus increased testicular steroidogenesis in hyperglycemia. Diabetes-associated hyperglycemia induced oxidative stress is a widely proven cause for diabetes-related male infertility. Our results collectively suggest that AQP 9 impairs testicular steroidogenesis via the regulation of oxidative stress in diabetes.

The possible role of sirtuins in male reproduction.

Global influence of male infertility is increasing in recent decades. Proper understanding of genetics, anatomy, physiology and the intricate interrelation of male reproductive system are much needed for explaining the etiology of male infertility; and a detailed study on the epigenetics, indeed, will reveal the molecular mechanism behind its etiology. Sirtuins, the molecular sensors, are NAD+ dependent histone deacetylases and ADP- ribosyl transferases, participate in the chief events of epigenetics. In mammals, sirtuin family comprises seven members (SIRT1-SIRT7), and they all possess a conserved NAD+ binding catalytic domain, termed the sirtuin core domain which is imperative for their activity. Sirtuins exert a pivotal role in cellular homeostasis, energy metabolism, apoptosis, age-related disorders and male reproductive system. However, their exact role in male reproduction is still obscure. This article specifically reviews the role of mammalian sirtuins in male reproductive function, thereby, prompting further research to discover the restorative methods and its implementation in reproductive medicine.

Could aquaporin modulators be employed as prospective drugs for COVID-19 related pulmonary comorbidity?

COVID-19 initially an epidemic caused by SARS-CoV-2 has turned out to be a life- threatening global pandemic with increased morbidity and mortality. The presence of cytokine storm has been linked with the pathogenesis of severe lung injury as evinced in COVID-19. Aquaporins (AQPs) are molecular water channels, facilitating water transport across the cell membrane in response to osmotic gradients. Impairment in alveolar fluid clearance due to altered functional expression of respiratory AQPs highlight their pathophysiological significance in pulmonary edema associated respiratory illness. Therefore, we hypothesize that targeted modulation of AQPs in lungs in the intervening period of time, could diminish the dreadful effects of inflammation- induced comorbidity in COVID-19.

Role of Aquaporins in Inflammation-a Scientific Curation.

Inflammation is a universal response mechanism existing as inter-communicator of biological systems. Uncontrolled or dysregulated inflammation addresses chronic low-grade effects eventually resulting in multimorbidity. Active solute transport across the membrane establishes varying osmotic gradients. Aquaporins (AQPs) are a class of critical ubiquitously expressed transmembrane proteins that aid in fluid and small solute transport via facilitated diffusion over established osmotic gradients. Numerous significant data features the biological functions of AQPs rendering them as an appropriate biomarker of health and diseases. Besides their physiological role in well-balanced inflammatory responses, it is worth noting the dysregulation of AQPs during any undesirable inflammatory event. Most literature to date clearly sets out AQPs as potential drug targets instigating AQP-based therapies. In light of this conception, the current review provides a compendious overview on the propitious and portentous out-turns of AQPs under inflammation.

Role of Aquaporins in Spermatogenesis and Testicular Steroidogenesis.

The transport of water and several other small molecules across cell membranes is vital in many of the processes underlying reproduction. Fluid transport in cells and tissues inclusive of male reproductive organs are regulated by disparate isoforms of aquaporins (AQPs) in living organisms. Alteration in the expression, function and/or regulation of AQPs leads to some forms of male subfertility and infertility. The emerging role of AQPs in male and female reproductive function has been revealed in recent times. However, the role of AQPs with reference to male reproductive system needs to be explored in greater detail. This review emphasizes the distribution of AQPs and their physiological and pathophysiological role in spermatogenesis and steroidogenesis; and understanding the molecular mechanisms behind AQPs mediated regulation of spermatogenesis and steroidogenesis will help us in developing treatment strategies towards improved reproductive health.

PAX proteins and their role in pancreas.

Gene regulatory factors that govern the expression of heritable information come in an array of flavors, chiefly with transcription factors, the proteins which bind to regions of specific genes and modulate gene transcription, subsequently altering cellular function. PAX transcription factors are sequence-specific DNA-binding proteins exerting its regulatory activity in many tissues. Notably, three members of the PAX family namely PAX2, PAX4 and PAX6 have emerged as crucial players at multiple steps of pancreatic development and differentiation and also play a pivotal role in the regulation of pancreatic islet hormones synthesis and secretion. Providing a comprehensive outline of these transcription factors and their primordial and divergent roles in the pancreas is far-reaching in contemporary diabetes research. Accordingly, this review furnishes an outline of the role of pancreatic specific PAX regulators in the development of the pancreas and its associated disorders.