Porcine vas deferens luminal pH is acutely increased by systemic xylazine administration

Data are accumulating to demonstrate that pH regulation in the male reproductive tract has a vital role in modulating sperm cell fertilizing capacity and, therefore, male fertility. Bicarbonate uptake by sperm cells is required for the achievement of motility levels required for fertilization. Vas deferens epithelial cells can carry out measurable bicarbonate secretion, but the available literature to date reports that the vas deferens luminal content is typically acidic. This study aimed to determine pH in the boar vas deferens lumen and whether modulatory mechanisms exist for regulation of pH in this compartment of the male reproductive tract. A fiber-optic pH probe was used to assess pH in the vas deferens of anesthetized adult boars. The mean pH, derived from multiple measurements at variable positions along the vas deferens lumen, was 7.39 ± 0.09. Furthermore, administration of xylazine, an alpha-2 adrenergic receptor agonist, rapidly (< 10 min) alkalinized the vas deferens lumen in most cases. Since the duct was transected proximal to the site of measurements, the observations rule out the possibility that alkalinization resulted from secretion in more proximal portions of the duct. These results indicate that the boar vas deferens lumen can be alkaline, and suggest that porcine vas deferens epithelia increase net bicarbonate secretion in vivo, following systemic alpha-2 adrenergic stimulation. This secretory response greatly changes the luminal environment to which sperm cells are exposed, which will initiate or enhance motility, and is expected to modulate male fertility

Critical evaluation of food intake and energy balance in young modern pentathlon athletes: a cross-sectional study

BACKGROUND: Modern pentathlon comprises five sports: fencing, swimming, equestrian jumping, and a combined event of pistol shooting and running. Despite the expected high energy demand of this sport, there are few studies that provide support for the nutritional recommendations for pentathletes. The purpose of the present study was to evaluate young modern pentathlon athletes with respect to body composition, biochemical profile, and consumption of food and supplements. METHODS: Fifty-six young modern pentathletes aged 13.5 ± 2.4 years participated in the study: 22 adolescent girls and 34 adolescent boys, weight 55.8 ± 13.3 kg, height 1.6 ± 0.1 m, and body fat 21.1 ± 3.1 %. Food consumption was analyzed through a 24-h recall method and food-frequency questionnaire. Assessment of body composition was carried out by checking anthropometric measures (body mass, height, and skinfolds) and using protocols according to participants’ age and sexual maturity. RESULTS: Male participants consumed less energy than the general recommendations for athletes from the American Dietetic Association (2749 ± 1024 kcal vs. 3113 ± 704 kcal, p < 0.01), whereas female participants consumed more energy than those recommendations (2558 ± 808 kcal vs. 2213 ± 4734 kcal, p < 0.01). Neither young men nor young women followed the carbohydrate intake recommendations for athletes (6.3 ± 2.5 g/kg/day and 6.6 ± 2.2 g/kg/day, respectively). Lipid and protein intakes corresponded to recommendations for both sexes; however, insufficient intakes of calcium, fruits, and vegetables were seen, as well as frequent consumption of baked goods and sugared soft drinks. CONCLUSIONS: Adolescent modern pentathlon athletes presented inadequate eating habits with respect to consumption of carbohydrates and energy. Many participants had insufficient intake of micronutrients, especially calcium. However, future research is needed that is aimed at elucidating the real nutritional demands for good physical performance in this sport and the impact of inadequate eating habits on performance, especially among young athletes who are in the growth-stage years and are exposed to intense physical exercise routines

Hedgehog signalling promotes germ cell survival in the rat testis

Hedgehog (Hh) signalling has a crucial role in testis development. Sertoli cell-derived desert hedgehog (DHH) guides the formation of testis cords and differentiation of foetal-type Leydig cells. Dhh mutant mice are infertile due to a block in germ cell differentiation, hypogonadism and hypoandrogenism. Hh signalling pathway components are also expressed in postnatal testis. In the rat testis the transcription factor of the Hh pathway, glioma-associated oncogene homologue (GLI1), is expressed by a wide variety of germ cells. This suggests that Hh signalling is involved in spermatogenesis at many different levels. Our data show that canonical Hh signalling is turned off in early condensing spermatids that strongly express the negative regulator of the pathway, suppressor of fused (SUFU). Most of the Hh pathway specific mRNAs display the highest values in stages II–VI of the rat seminiferous epithelial cycle. The key endocrine regulator of germ cell differentiation, FSH, down-regulates Dhh mRNA levels in vitro. Hh signalling inhibition in vitro leads to massive apoptosis of germ cells. In prepubertal rat testis imatinib mesylate-induced inhibition of tyrosine kinases impinges on Dhh transcript levels and Hh signalling. Our data indicate that Hh signalling is part of the paracrine signalling network in the rat testis. It promotes the survival of germ cells and is suppressed by FSH

Effect of environmental and pharmaceutical exposures on fetal testis development and function:a systematic review of human experimental data

BACKGROUND: Overall, the incidence of male reproductive disorders has increased in recent decades. Testicular development during fetal life is crucial for subsequent male reproductive function. Non-genomic factors such as environmental chemicals, pharmaceuticals and lifestyle have been proposed to impact on human fetal testicular development resulting in subsequent effects on male reproductive health. Whilst experimental studies using animal models have provided support for this hypothesis, more recently a number of experimental studies using human tissues and cells have begun to translate these findings to determine direct human relevance.OBJECTIVE AND RATIONALE: The objective of this systematic review was to provide a comprehensive description of the evidence for effects of prenatal exposure(s) on human fetal testis development and function. We present the effects of environmental, pharmaceutical and lifestyle factors in experimental systems involving exposure of human fetal testis tissues and cells. Comparison is made with existing epidemiological data primarily derived from a recent meta-analysis.SEARCH METHODS: For identification of experimental studies, PubMed and EMBASE were searched for articles published in English between 01/01/1966 and 13/07/2018 using search terms including 'endocrine disruptor', 'human', 'fetal', 'testis', 'germ cells', 'testosterone' and related search terms. Abstracts were screened for selection of full-text articles for further interrogation. Epidemiological studies involving exposure to the same agents were extracted from a recent systematic review and meta-analysis. Additional studies were identified through screening of bibliographies of full-texts of articles identified through the initial searches.OUTCOMES: A total of 25 experimental studies and 44 epidemiological studies were included. Consistent effects of analgesic and phthalate exposure on human fetal germ cell development are demonstrated in experimental models, correlating with evidence from epidemiological studies and animal models. Furthermore, analgesic-induced reduction in fetal testosterone production, which predisposes to the development of male reproductive disorders, has been reported in studies involving human tissues, which also supports data from animal and epidemiological studies. However, whilst reduced testosterone production has been demonstrated in animal studies following exposure(s) to a variety of environmental chemicals including phthalates and bisphenol A, these effects are not reproduced in experimental approaches using human fetal testis tissues.WIDER IMPLICATIONS: Direct experimental evidence for effects of prenatal exposure(s) on human fetal testis development and function exists. However, for many exposures the data is limited. The increasing use of human-relevant models systems in which to determine the effects of environmental exposure(s) (including mixed exposures) on development and function of human tissues should form an important part of the process for assessment of such exposures by regulatory bodies to take account of animal-human differences in susceptibility.</p

Da tolerância à caridade: sobre religião, laicidade e pluralismo na atualidade

ResumoAs questões da (in)tolerância entre as religiões e da liberdade de crença e de pensamento não são novas para a história, ou melhor, não são exclusivas desta época. Basta lembrar, para os propósitos aqui arrolados, uma obra do período iluminista, o Tratado sobre a tolerância de Voltaire, que tratava precisamente disto. Em contrapartida, mesmo vivendo numa era de consolidação de fenômenos de secularização, como Gianni Vattimo entende ser a nossa – e que tem a ver com liberdade, celebração e respeito às diferenças –, ainda se vislumbra a intolerância para com diferentes crenças religiosas, e o não respeito, especialmente por parte de setores de religiões majoritárias como o cristianismo, ao princípio de laicidade do Estado. Em diálogo com o pensiero debole (pensamento fraco) de Vattimo, analisarei a proposta deste autor de migração da ideia de tolerância para a de caridade, como meio de mover-se para além de uma relação metafísica com a verdade nas religiões para a noção pouco comum às práticas e discursos religiosos de uma verdade kenótica, isto é, esvaziada de pretensões de correspondência e, por conseguinte, de imposição sobre outras

Mammalian sex determination—insights from humans and mice

Disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical. Many of the genes required for gonad development have been identified by analysis of DSD patients. However, the use of knockout and transgenic mouse strains have contributed enormously to the study of gonad gene function and interactions within the development network. Although the genetic basis of mammalian sex determination and differentiation has advanced considerably in recent years, a majority of 46,XY gonadal dysgenesis patients still cannot be provided with an accurate diagnosis. Some of these unexplained DSD cases may be due to mutations in novel DSD genes or genomic rearrangements affecting regulatory regions that lead to atypical gene expression. Here, we review our current knowledge of mammalian sex determination drawing on insights from human DSD patients and mouse models