Growth Hormone and Insulin-like Growth Factor-I: Novel Insights into the Male Reproductive Health

The roles of growth hormone (GH) in male reproductive health are summarized in this chapter. It has been evident in several studies that GH plays a vital physiological role in the regulation of male reproductive development and function, while the excessive release of GH can interfere with male reproductive health, sexual behavior, and fertility potentials. Several classical functions of GH include cellular proliferation, differentiation, development, and metabolism, although vast literature specifies their role in reproductive function in both humans and animals. Moreover, evidence from several studies have suggested both deficiency and overproduction of GH in adults are associated with several pathophysiological conditions, viz., metabolic derangements, central adiposity, dyslipidemia, and insulin resistance. The GH exerts its beneficial role by binding and activation to GH-receptors (GH-Rs), expressed at several target tissues, viz., in the hypothalamus and other parts of the central nervous system, and in the male gonad (testis), including Leydig and Sertoli cells. The GH may reflect either by local autocrine or paracrine actions or by the endocrine actions. The release of certain GH such as insulin-like growth factor 1 (IGF-1) plays a crucial role in the regulation of male reproductive physiology, while the excessive release of GH can interfere with male sexual behavior and fertility

Direct actions of adiponectin on changes in reproductive, metabolic, and anti-oxidative enzymes status in the testis of adult mice

Accepted manuscriptObesity is a major health problem that is linked to decreased sperm count. It is hypothesized that an obesity-associated reduction in adiponectin secretion may be responsible for impairment of spermatogenesis. Therefore, the aim of the study was to evaluate the direct role of adiponectin in spermatogenesis and steroid synthesis in adult mice. This study showed that adiponectin receptors (AdipoR1 and AdipoR2) were localized in Leydig cells and seminiferous tubules in the testis of adult mice. The result of the in vitro study showed the direct action of adiponectin on spermatogenesis by stimulating cell proliferation (PCNA) and survival (Bcl2) and by suppressing cell apoptosis. Treatment of testis with adiponectin also enhanced transport of the energetic substrates glucose and lactate to protect cells from undergoing apoptosis. Adiponectin treatment further showed a significant reduction in oxidative stress and nitric oxide. Our findings suggest that adiponectin effectively facilitates cell survival and proliferation, as well as protects from apoptosis. Thus, adiponectin treatment may be responsible for enhancing sperm counts. Interestingly, this study showed the stimulatory effect of adiponectin in spermatogenesis but showed an inhibitory effect on testosterone and estradiol synthesis in the testes. Based on the present study, it is hypothesized that systemic adiponectin treatment may be a promising therapeutic strategy for the improvement of spermatogenesis and sperm count.University Grants Commission, New-Delhi, India. The authors would like to thank DeAnn Hubberd and Madison Hedrick from the Science Communications Department at the University of Arkansas for Medical Sciences for their work editing this manuscript. This work was also supported by Centre of Advanced Study, Department of Zoology, Banaras Hindu University, Varanasi, Indiainfo:eu-repo/semantics/acceptedVersio

Role of adiponectin as a modulator of testicular function during aging in mice

The mechanisms by which testicular functions decline with aging remain largely speculative. Our recent finding showed the importance of adiponectin in the regulation of testicular functions, whereas its concentration declines during male infertility. Thus, the aim of present study was to explore the potential role of adiponectin during aging. The changes in adiponectin, adiponectin-receptors, and insulin receptor proteins expression in the testis were evaluated and compared with the testicular parameters, mass, and testosterone level in the mice from early post-natal to late senescence period. Further, the current study has examined the effect of exogenous adiponectin treatment on testicular functions in aged mice. The results showed a significant decline in adiponectin/adiponectin-receptors expression simultaneously with a significant decline in testicular mass, insulin receptor expression and testosterone synthesis in the testis of aged mice. Exogenous treatment of adiponectin to aged mice resulted in marked improvements in testicular mass, histological features (cells proliferation), insulin receptor expression, testicular glucose uptake, anti-oxidative enzymes activity and testosterone synthesis as compared with the control. Based on these findings, it may be concluded that a marked decline in adiponectin synthesis and action results in decreased insulin sensitivity (development of insulin resistance) and increased oxidative stress which consequently suppresses testicular functions during aging. This study further showed that treatment with adiponectin ameliorates reduced testicular functions by enhanced expression of insulin receptor in the testis of senescent mice. It is thus hypothesized that systemic adiponectin treatment could be a promising therapeutic strategy for improvement of testosterone production and sperm counts during aging.Mayank Choubey greatly acknowledges financial assistance in the form of a Senior Research Fellowship (SRF) from Indian Council of Medical Research (ICMR File No. RBMH/FW/2018/1), New Delhi, India. This work was also supported by University Grant Commission (UGC), New Delhi and Centre of Advanced Study, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, India

Robust generation of transgenic mice by simple hypotonic solution mediated delivery of transgene in testicular germ cells

Our ability to decipher gene sequences has increased enormously with the advent of modern sequencing tools, but the ability to divulge functions of new genes have not increased correspondingly. This has caused a remarkable delay in functional interpretation of several newly found genes in tissue and age specific manner, limiting the pace of biological research. This is mainly due to lack of advancements in methodological tools for transgenesis. Predominantly practiced method of transgenesis by pronuclear DNA-microinjection is time consuming, tedious, and requires highly skilled persons for embryo-manipulation. Testicular electroporation mediated transgenesis requires use of electric current to testis. To this end, we have now developed an innovative technique for making transgenic mice by giving hypotonic shock to male germ cells for the gene delivery. Desired transgene was suspended in hypotonic Tris-HCl solution (pH 7.0) and simply injected in testis. This resulted in internalization of the transgene in dividing germ-cells residing at basal compartment of tubules leading to its integration in native genome of mice. Such males generated transgenic progeny by natural mating. Several transgenic animals can be generated with minimum skill within short span of time by this easily adaptable novel technique

Modeling of Vibration Assisted Micro Electrical Discharge Machining for Fabrication of Micro Holes in Inconel 718

Owing to the increasing trend towards miniature and lightweight components for various applications, manufacturing industries are developing new technologies to meet the unique challenges posed by micro manufacturing. Fabrication of micro-sized components using micro-EDM is one of the significant steps towards miniaturization. The inherent characteristic of micro-EDM is the capability of machining of three-dimensional complex micro-components used in biomedical, optical, aerospace, automobile, and electronics industries. Due to the high accuracy of machined parts and lower machining cost, micro-EDM becomes a more promising method used for the machining of difficult-to-machine materials like Inconel 718. Despite several advantages, micro-EDM alone cannot satisfy the numerous prerequisites of the machine parts because of few disadvantages like low machining rate and high tool wear. The characteristics of micro-EDM are influenced by several controllable process parameters, which make it difficult to locate the optimum parameters without understanding the mechanism of material removal rate. Therefore, there is a need to understand the fundamentals of process mechanism by developing a numerical model for micro-EDM process. The aim of this research is to develop the FEM based thermal model for the micro-EDM process to understand the crater formation and material removal rate on the surface of the workpiece. Initially, the finite element analysis was carried out to obtain the crater geometry and temperature distribution on the workpiece surface due to single spark in the micro-EDM process. The developed model proposes to enable the understanding of temperature distribution and shape of the crater in the micro-EDM process without workpiece-vibration. Further, the thermal model for vibration-assisted micro-EDM has been developed to understand the crater morphology and material removal mechanism in micro-EDM with aid of workpiece vibration. A numerical simulation has also been carried out to simulate the flushing of the debris from the gap between the electrodes when there was no vibration and when a vibration was applied to the workpiece in the micro-EDM process. In the second phase of this research, an experimental investigation has been carried out on micro-EDM operation in Inconel 718 to validate the simulation results without vibration of the workpiece. A parametric study has been carried out to analyze the effect of the process parameters on material removal rate, accuracy and surface quality of the fabricated micro-holes in Inconel 718

Linking Adiponectin and Its Receptors to Age-Related Macular Degeneration (AMD)

In recent years, there has been a captivating focus of interest in elucidating the intricate crosstalk between adiponectin (APN), a versatile fat-associated adipokine and ocular pathologies. Unveiling the intricate relationship between adipocytokine APN and its receptors (AdipoRs) with aging eye disorders has emerged as a fascinating frontier in medical research. This review article delves into this connection, illuminating the hidden influence of APN on retinal health. This comprehensive review critically examines the latest findings and breakthroughs that underscore the pivotal roles of APN/AdipoRs signaling in maintaining ocular homeostasis and protecting against eye ailments. Here, we meticulously explore the intriguing mechanisms by which APN protein influences retinal function and overall visual acuity. Drawing from an extensive array of cutting-edge studies, the article highlights APN’s multifaceted functions, ranging from anti-inflammatory properties and oxidative stress reduction to angiogenic regulation within retinal and macula tissues. The involvement of APN/AdipoRs in mediating these effects opens up novel avenues for potential therapeutic interventions targeting prevalent aging eye conditions. Moreover, this review unravels the interplay between APN signaling pathways and age-related macular degeneration (AMD). The single-cell RNA-seq results validate the expression of both the receptor isoforms (AdipoR1/R2) in retinal cells. The transcriptomic analysis showed lower expression of AdipoR1/2 in dry AMD pathogenesis compared to healthy subjects. The inhibitory adiponectin peptide (APN1) demonstrated over 75% suppression of CNV, whereas the control peptide did not exert any inhibitory effect on choroidal neovascularization (CNV). The elucidation of these relationships fosters a deeper understanding of adipose tissue’s profound influence on ocular health, presenting new prospects for personalized treatments and preventative measures. Because APN1 inhibits CNV and leakage, it can be used to treat human AMD, although the possibility to treat human AMD is in the early stage and more clinical research is needed. In conclusion, this review provides a captivating journey into the enthralling world of APN, intertwining the realms of adipose biology and ophthalmology in aging

Stem Cell Therapy in Diabetic Polyneuropathy: Recent Advancements and Future Directions

Diabetic polyneuropathy (DPN) is the most frequent, although neglected, complication of long-term diabetes. Nearly 30% of hospitalized and 20% of community-dwelling patients with diabetes suffer from DPN; the incidence rate is approximately 2% annually. To date, there has been no curable therapy for DPN. Under these circumstances, cell therapy may be a vital candidate for the treatment of DPN. The epidemiology, classification, and treatment options for DPN are disclosed in the current review. Cell-based therapies using bone marrow-derived cells, embryonic stem cells, pluripotent stem cells, endothelial progenitor cells, mesenchymal stem cells, or dental pulp stem cells are our primary concern, which may be a useful treatment option to ease or to stop the progression of DPN. The importance of cryotherapies for treating DPN has been observed in several studies. These findings may help for the future researchers to establish more focused, accurate, effective, alternative, and safe therapy to reduce DPN. Cell-based therapy might be a permanent solution in the treatment and management of diabetes-induced neuropathy

The Effect of COVID-19 on Gut Microbiota: Exploring the Complex Interplay and Implications for Human Health

The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to significant global health implications. Although the respiratory manifestations of COVID-19 are widely recognized, emerging evidence suggests that the disease may also significantly affect the gut microbiota, the intricate community of bacteria that lives within the gastrointestinal system. This extensive article intends to investigate the impact of COVID-19 on the gut microbiota, examining the underlying mechanisms, clinical implications, and potential therapeutic interventions. Understanding the complex interactions between COVID-19 and the gut microbiota will help us to gain valuable insights into the broader consequences of this viral infection on human health

Adiponectin: A Promising Target for the Treatment of Diabetes and Its Complications

Diabetes mellitus, a chronic metabolic disorder characterized by hyperglycemia, presents a formidable global health challenge with its associated complications. Adiponectin, an adipocyte-derived hormone, has emerged as a significant player in glucose metabolism and insulin sensitivity. Beyond its metabolic effects, adiponectin exerts anti-inflammatory, anti-oxidative, and vasoprotective properties, making it an appealing therapeutic target for mitigating diabetic complications. The molecular mechanisms by which adiponectin impacts critical pathways implicated in diabetic nephropathy, retinopathy, neuropathy, and cardiovascular problems are thoroughly examined in this study. In addition, we explore possible treatment options for increasing adiponectin levels or improving its downstream signaling. The multifaceted protective roles of adiponectin in diabetic complications suggest its potential as a novel therapeutic avenue. However, further translational studies and clinical trials are warranted to fully harness the therapeutic potential of adiponectin in the management of diabetic complications. This review highlights adiponectin as a promising target for the treatment of diverse diabetic complications and encourages continued research in this pivotal area of diabetes therapeutics