Undernutrition Affects Cell Survival,Oxidative Stress,Ca2+ Handling and Signaling Pathways in Vas Deferens,Crippling Reproductive Capacity

Background

The aim of this work was to investigate the mechanisms by which chronic malnutrition (CM) affects vas deferens function, leading to compromised reproductive capacity. Previous studies have shown that maternal malnutrition affects the reproductive tracts of adult male offspring. However, little is known about the effects of CM, a widespread life-long condition that persists from conception throughout growth to adult life.

Methodology/Principal Findings

Young adult male rats, which were chronically malnourished from weaning, presented decreased total and haploid cells in the vas deferens, hypertrophy of the muscle layer in the epididymal portion of the vas deferens and intense atrophy of the muscular coat in its prostatic portion. At a molecular level, the vas deferens tissue of CM rats exhibited a huge rise in lipid peroxidation and protein carbonylation, evidence of an accentuated increase in local reactive oxygen species levels. The kinetics of plasma membrane Ca²⁺-ATPase activity and its kinase-mediated phosphorylation by PKA and PKC in the vas deferens revealed malnutrition-induced modifications in velocity, Ca²⁺ affinity and regulation of Ca²⁺ handling proteins. The severely crippled content of the 12-kDa FK506 binding protein, which controls passive Ca²⁺ release from the sarco(endo) plasmic reticulum, revealed another target of malnutrition related to intracellular Ca²⁺ handling, with a potential effect on forward propulsion of sperm cells. As a possible compensatory response, malnutrition led to enhanced sarco(endo) plasmic reticulum Ca²⁺-ATPase activity, possibly caused by stimulatory PKA-mediated phosphorylation.

Conclusions/Significance

The functional correlates of these cellular and molecular hallmarks of chronic malnutrition on the vas deferens were an accentuated reduction in fertility and fecundity.     

Discriminating Males and Unpredictable Females: Males Bias Sperm Allocation in Favor of Virgin Females

When both sexes mate with multiple partners, theory predicts that males should adjust their investment in ejaculates in response to the risk and/or intensity of sperm competition. Here, we demonstrate that, in the harlequin beetle riding pseudoscorpion, Cordylochernes scorpioides, males use cues deposited on females by previous males to distinguish between virgin, once‐mated, and multiply‐mated females and adjust sperm allocation accordingly. Sperm number declined in direct proportion to the number of previous males, with virgin females receiving nearly three times more sperm than females exposed to three previous males. Given the lack of first‐male sperm precedence in C. scorpioides, this pattern is not consistent with current sperm competition models and appears best explained by a significant risk of wasting ejaculates on deceitful, mated females. In C. scorpioides, males transfer sperm indirectly to females via a stalked spermatophore deposited on the substrate. Mated females often feign sexual receptivity and cooperate throughout mating, only to reject the sperm packet produced by the male. While indirect sperm transfer facilitates a high level of female deceit and control, females of many species are able to influence the number and fate of sperm transferred during copulation and are likely to conceal their sexual unreceptivity to minimize male retaliation. If males cannot accurately assess female receptivity, increased risk of sperm rejection by mated females could outweigh the risk of sperm competition and favor greater sperm allocation to virgin females.     

Oxidative Stress and Redox-Dependent Signaling in Prostate Cancer

Biochemistry (Moscow) - Tumor emergence and progression is complicated by the dual role of reactive oxygen species (ROS). Low concentrations of ROS are essential for many intracellular metabolic...     

Role of Selenium on Calcium Signaling and Oxidative Stress-induced Molecular Pathways in Epilepsy

Epilepsy is one of the oldest neurological conditions known to humankind. It is known that oxidative stress and generation of reactive oxygen species are a cause and consequence of epileptic seizures. Although recent years have seen tremendous progress in the molecular biology and metabolism of selenium, we still know little about the cell type-specific and temporal pattern of selenium and its derivatives in the brain of epileptic humans and experimental animals. It has been suggested that some antiepileptic drug therapies such as valproic acid, deplete the total body selenium level and selenium-dependent glutathione peroxidase (GSH-Px) activity although therapy with a new epileptic drug, topiramate, activated GSH-Px activity in epileptic animals and humans. An observation of lower blood or tissue selenium level and GSH-Px activity in epileptic patients and animals compared to controls in recent publications may support the proposed crucial role of selenium level and GSH-Px activity in the pathogenesis of epilepsy. Selenium is incorporated into an interesting class of molecules known as selenoproteins that contain the modified amino acid, selenocysteine. There are signs of selenium and selenoprotein deficiency in the pathogenesis of epilepsy. In conclusion, there is convincing evidence for the proposed crucial role of selenium and deficiency of GSH-Px enzyme activity in epilepsy pathogenesis. Blood GSH-Px activities could be a reliable indicator of selenium deficiency in patients with epilepsy.     

微RNAs与内质网应激信号通路的相互调控作用

内质网应激(endoplasmic reticulum stress,ERS)是为恢复稳态和减轻蛋白质负荷的一种细胞防御性反应.过度激活的ERS可诱导细胞分化、增殖、凋亡和自噬等.微RNAs(microRNAs,miRNAs)作为一种内源性的非编码RNA(non-coding RNA,ncRNA),可通过转录后作用调控...     

Role of Oxidative Stress and Ca2+ Signaling on Molecular Pathways of Neuropathic Pain in Diabetes: Focus on TRP Channels

Diabetes mellitus, a debilitating chronic disease, affects ~100?million people. Peripheral neuropathy is one of the most common early complications of diabetes in ~66?% of these patients. Altered Ca(2+) handling and Ca(2+) signaling were detected in a huge variety of preparations isolated from animals with experimentally induced type 1 and 2 diabetes as well as patients suffering from the disease. We reviewed the role of Ca(2+) signaling through cation channels and oxidative stress on diabetic neuropathic pain in sensory neurons. The pathogenesis of diabetic neuropathy involves the polyol pathway, advanced glycation end products, oxidative stress, protein kinase C activation, neurotrophism, and hypoxia. Experimental studies with respect to oxidative stress and Ca(2+) signaling, inhibitor roles of antioxidants in diabetic neuropathic pain are also summarized in the review. We hypothesize that deficits in insulin, triggers alterations of sensory neurone phenotype that are critical for the development of abnormal Ca(2+) homeostasis and oxidative stress and associated mitochondrial dysfunction. The transient receptor potential channels are a large family of proteins with six main subfamilies. The sheer number of different TRPs with distinct functions supports the statement that these channels are involved in a wide range of processes ranging in diabetic neuropathic pain and it seems that the TRPC, TRPM and TRPV groups are mostly responsible from diabetic neuropathic pain. In conclusion, the accumulating evidence implicating Ca(2+) dysregulation and over production of oxidative stress products in diabetic neuropathic pains, along with recent advances in understanding of genetic variations in cation channels such as TRP channels, makes modulation of neuronal Ca(2+) handling an increasingly viable approach for therapeutic interventions against the painful and degenerative aspects of many diabetic neuropathies.     

昆明地区滇蛙两性生殖器官的生长及发育同步性

月平均采集并解剖滇蛙14—16只(雌雄约各半),测量体长、体重、脂肪体重、精巢重、卵巢重、精巢体积和输卵管直径等。以体长为协变量做协方差分析,结果显示,精巢重、卵巢重、精巢体积、输卵管直径在年周期内差异显著,呈周年规律性变化。滇蛙的繁殖期为4—6月,5月下旬至6月上旬为繁殖高峰。异速生长分析和回归分析结果显示,性腺发育与体重和体长多呈正异速生长(b>1),个体增长对性腺的发育有显著影响。个体较大的滇蛙年生殖频次至少为2次,这是提高繁殖成功率的繁殖策略之一。性腺发育与脂肪体重呈负异速生长(b<1)。脂肪体为繁殖和冬眠提供能量储备,脂肪体重在繁殖高峰期达最小值。少数脂肪储存不足的个体通过延迟冬眠时间积累能量,以便安全越冬。相关性分析和交叉相关分析结果显示,两性生殖腺的发育具有显著的相关性,但生殖腺的发育并非完全同步。雄蛙精巢的发育具有一定的滞后性,因为卵的成熟比精子的成熟需要更长的时间。但精巢体积和输卵管直径发育具同步性,这恰是为授精做好了准备。     

Exploiting Oxidative Stress and Signaling in Chemotherapy of Resistant Neoplasms

Neural crest tumors of childhood are particularly resistant to apoptosis induction by chemotherapeutic agents. Mechanisms of resistance include altered glutathione handling that accompanies up-regulation of Bcl-2 and its relatives. We have designed and tested in preclinical model systems approaches to this problem. These approaches include adjunctive use of oxygen radical-generating neurotransmitter analogs taken up by these neural crest tumor cells with scavenging (i.e., "rescue") agents that are selective for normal neural crest and the use of reduction-dependent prodrugs of apoptosis-inducing agents. Promising prototypes for these conceptual approaches include, respectively, adjunctive use of the oxygen radical generator, 6-hydroxydopamine, with the normal cell-selective antioxidant, Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), and use of the reduction-dependent chemotherapeutic prodrug neocarzinostatin.     

铅对雄性生殖毒性的研究进展

从铅对睾丸与附睾形态、精子生成和发育以及生殖内分泌功能等三方面的影响综述了铅对雄性生殖毒性的研究进展;并从铅对睾丸的脂质过氧化损伤,对睾丸标志酶活性的影响,对染色体、DNA及基因的影响以及对CaM、Ca2 -ATP酶活性的影响等方面探讨了铅对雄性生殖毒性作用机理。同时,提出了铅对雄性生殖毒性的研究中存在的若干问题和发展方向。     

基于SOS反应及氧化应激反应相关启动子的辐射生物传感器研究

近年来的动物实验结果表明电磁辐射的危害主要是具有神经系统毒性、诱发肿瘤和生殖系统损伤等,广域、隐蔽和累积效应是辐射的特点,除对机体进行直接损伤外,还可导致间接损伤,即通过产生活性氧(ROS)和自由基攻击生物大分子。为了迅速和简便地检测辐射毒性的大小建立了新型的辐射生物传感器,构建了携带SOS反应和氧化应激反应相关的SulA、RecA、Cda和SoxR四种启动子融合经过密码子简并性优化的增强型绿色荧光蛋白(enhanced green fluorescent protein,EGFP)报告因子的工程菌传感器,并对这些生物传感器进行了γ射线辐照处理,筛选出了针对γ射线响应较好的,优选RecA工程菌传感器。利用PCR和Overlap PCR克隆获得了启动子-报告因子融合基因,并插入表达载体PUC19中,转化入宿主大肠杆菌DH5α,通过提取质粒进行双酶切和测序验证后,将构建成功的工程菌传感器首先进行化学毒性试剂刺激,一旦化学试剂刺激结果阳性便进行物理辐射刺激。结果显示,构建成功的4种工程菌传感器均对物理辐射产生应答,且随物理辐射剂量的增加(0～30Gy),绿色荧光强度逐渐增强。运用合成生物学手段,成功建立基于生物损伤修复效应和氧化应激反应的辐射生物传感器,具有制备简便、结果可视性等优点,能满足快速、广范围、在线监测的需求,在细胞毒性物、辐射环境乃至空间射线的损伤能力测定方面具有良好的应用前景。     

A Combined Approach to Heat Stress Effect on Male Fertility in Nasonia vitripennis: From the Physiological Consequences on Spermatogenesis to the Reproductive Adjustment of Females Mated with Stressed Males

In recent years, several studies have shown a decline in reproductive success in males in both humans and wildlife. Research on male fertility has largely focused on vertebrates, although invertebrates constitute the vast majority of terrestrial biodiversity. The reduction of their reproductive capacities due to environmental stresses can have strong negative ecological impacts, and also dramatic consequences on world food production if it affects the reproductive success of biological control agents, such as parasitic wasps used to control crop pests. Here Nasonia vitripennis, a parasitic wasp of various fly species, was studied to test the effects of 24h-heat stress applied during the first pupal stage on male fertility. Results showed that only primary spermatocytes were present at the first pupal stage in all cysts of the testes. Heat stress caused a delay in spermatogenesis during development and a significant decrease in sperm stock at emergence. Females mated with these heat-stressed males showed a reduce sperm count stored in their spermatheca. Females did not appear to distinguish heat-stressed from control males and did not remate more frequently to compensate for the lack of sperm transferred. As a result, females mated with heat-stressed males produced a suboptimal lifetime offspring sex ratio compared to those mated with control males. This could further impact the population dynamics of this species. N. vitripennis appears to be an interesting biological model to study the mechanisms of subfertility and its consequence on female reproductive strategies and provides new research perspectives in both invertebrates and vertebrates.     

Systemic Non-Reproductive Effects of Sex Steroids in Adult Males and Females

Sex steroids are well known for their reproductive actions, however, their roles are not confined to reproduction only and they have been shown to exert wide ranging effects on systemic physiology. Further, the effects of the so-called male and female sex steroids are not limited to their respective genders but they are present in both sexes where they have a significant impact upon systemic functions, reproductive as well as non-reproductive. This work reviews the existing knowledge base and recent reports on the effects of sex steroids on non-reproductive physiology.     

Opposing Roles of Mitogenic and Stress Signaling Pathways in the Induction of Cancer Dormancy

Cancer dormancy is a poorly understood stage of cancer progression. However, the ability to control this step of the disease offers novel therapeutic opportunities. Here we summarize recent findings that implicate the extracellular matrix and adhesion receptor signaling in the escape or induction of tumor dormancy. We further review evidence suggesting that imbalances in the activity ratio of ERK to p38 signaling may determine the fate (i.e. tumorigenicity vs. dormancy) of different carcinoma cells. Special attention is placed on the mechanisms that p38 signaling regulates during the induction of dormancy and how modulation of these pathways may offer a therapeutic opportunity. We also review evidence for a novel drug-resistance mechanism in dormant tumor cells that when blocked may enable killing of dormant tumor cells. Finally, we explore the notion that dormancy of tumor cells may be the result of a selective adaptive response that allows disseminated tumor cells to pause their growth and cope with stress signaling imposed by dissemination and/or treatment until growth can be restored.