Absence of Inhibin Alpha and Retinoblastoma Protein Leads to Early Sertoli Cell Dysfunction

Sertoli cells, the support cells of mammalian spermatogenesis, are regulated by a number of nuclear factors and express retinoblastoma (RB) tumor suppressor protein. We hypothesized that RB is an important mediator of Sertoli cell tumorigenesis in inhibin α knockout (Inha KO) mice. In our previous mouse studies, we found that conditional knockout (cKO) of Rb in Sertoli cells caused progressive Sertoli cell dysfunction. Initially, loss of RB had no gross effect on Sertoli cell function as the mice were fertile with normal testis weights at 6 weeks of age, but by 10–14 weeks of age, mutant mice demonstrated severe Sertoli cell dysfunction and infertility. Although double knockout (dKO) of Rb and Inha did not result in exacerbation of the tumorigenic phenotype of Inha-null mice, we found that the dKO mice demonstrate an acceleration of Sertoli cell dysfunction compared to Rb cKO mice. Specifically, in contrast to Rb cKO mice, Inha/Rb dKO mice showed signs of Sertoli cell dysfunction as early as 4 weeks of age. These results demonstrate that RB is not essential for Sertoli cell tumorigenesis in Inha KO mice but that loss of Inha accelerates the infertility phenotype of Rb cKO mice

Attitudes towards fibromyalgia: A survey of Canadian chiropractic, naturopathic, physical therapy and occupational therapy students

<p>Abstract</p> <p>Background</p> <p>The frequent use of chiropractic, naturopathic, and physical and occupational therapy by patients with fibromyalgia has been emphasized repeatedly, but little is known about the attitudes of these therapists towards this challenging condition.</p> <p>Methods</p> <p>We administered a cross-sectional survey to 385 senior Canadian chiropractic, naturopathic, physical and occupational therapy students in their final year of studies, that inquired about attitudes towards the diagnosis and management of fibromyalgia.</p> <p>Results</p> <p>336 students completed the survey (response rate 87%). While they disagreed about the etiology (primarily psychological 28%, physiological 23%, psychological and physiological 15%, unsure 34%), the majority (58%) reported that fibromyalgia was difficult to manage. Respondants were also conflicted in whether treatment should prioritize symptom relief (65%) or functional gains (85%), with the majority (58%) wanting to do both. The majority of respondents (57%) agreed that there was effective treatment for fibromyalgia and that they possessed the required clinical skills to manage patients (55%).</p> <p>Chiropractic students were most skeptical in regards to fibromyalgia as a useful diagnostic entity, and most likely to endorse a psychological etiology. In our regression model, only training in naturopathic medicine (unstandardized regression coefficient = 0.33; 95% confidence interval = 0.11 to 0.56) and the belief that effective therapies existed (unstandardized regression coefficient = 0.42; 95% confidence interval = 0.30 to 0.54) were associated with greater confidence in managing patients with fibromyalgia.</p> <p>Conclusion</p> <p>The majority of senior Canadian chiropractic, naturopathic, physical and occupational therapy students, and in particular those with naturopathic training, believe that effective treatment for fibromyalgia exists and that they possess the clinical skillset to effectively manage this disorder. The majority place high priority on both symptom relief and functional gains when treating fibromyalgia.</p

Reactive oxygen species and male reproductive hormones

Reports of the increasing incidence of male infertility paired with decreasing semen quality have triggered studies on the effects of lifestyle and environmental factors on the male reproductive potential. There are numerous exogenous and endogenous factors that are able to induce excessive production of reactive oxygen species (ROS) beyond that of cellular antioxidant capacity, thus causing oxidative stress. In turn, oxidative stress negatively affects male reproductive functions and may induce infertility either directly or indirectly by affecting the hypothalamus-pituitary-gonadal (HPG) axis and/or disrupting its crosstalk with other hormonal axes. This review discusses the important exogenous and endogenous factors leading to the generation of ROS in different parts of the male reproductive tract. It also highlights the negative impact of oxidative stress on the regulation and cross-talk between the reproductive hormones. It further describes the mechanism of ROS-induced derangement of male reproductive hormonal profiles that could ultimately lead to male infertility. An understanding of the disruptive effects of ROS on male reproductive hormones would encourage further investigations directed towards the prevention of ROS-mediated hormonal imbalances, which in turn could help in the management of male infertility