卵母细胞在哺乳动物卵巢排卵过程中的决定性作用

哺乳动物卵巢排卵是一个复杂的调控过程。卵泡成熟破裂后,卵母细胞从卵巢中排出。卵泡细胞感受排卵刺激,并诱导卵母细胞减数分裂的恢复及其随后的释放。卵母细胞及其周围颗粒细胞的旁分泌在对此起关键性作用,其中卵母细胞对其释放具有决定性作用。作者先前已经阐述过颗粒细胞在哺乳动物卵巢排卵过程中的调控作用,该文将从卵母细胞的发育及其调控角度重点阐明其在排卵过程中的决定作用,旨在进一步理解哺乳动物卵巢的排卵过程,同时为不孕不育等卵巢疾病的治疗提供重要的研究方向和理论基础。     

低氧诱导因子与低氧性肺动脉高压发病机制的研究进展

低氧性肺动脉高压(HPH)是慢性肺源性心脏病和慢性高原病等发病的重要病理生理变化之一,其特点主要是以低氧性肺血管收缩反应增强和肺小动脉中层平滑肌细胞的异常增生(重建)为主。虽然HPH的发病机制仍不清楚,但近来研究表明内皮素(ET)、血管内皮生长因子(VEGF)、促红细胞生成素(Epo)和一氧化氮(NO)是HPH的重要致病因子。它们可在低氧诱导因子—1(HIF—1α)介导或在增加的血流切应力和氧应激反应刺激下产生,并发挥相应的作用。本文将对HIF在低氧性肺动脉高压发病中的重要作用及其进展作一简要概述。     

低氧微环境中肿瘤的能量代谢

处于低氧微环境中的肿瘤细胞,其血管生成和代谢方式的改变使之能在低氧环境中生存及增殖。Warburg早已发现肿瘤细胞的代谢方式的改变．即在有氧环境中也优先利用糖酵解而非有氧呼吸来获得能量。与有氧呼吸有关的酶,如COX、SDH、FH,发生改变及抑癌基因p53的突变与其发生机制有关。     

低氧诱导因子-1的结构、功能、调节及其与低氧信号转导的关系

在许多类型细胞均发现低氧可诱导低氧诱导因子-1（HIF-1）水平的 增高,说明存在一个普遍的氧感受和低氧信号转导机制,其中HIF-1起着重要的作用。本文 综述了HIF-1的结构、功能和活性调节及其与低氧信号转导的关系等方面的研究进展。     

哺乳动物低氧应激代谢成因的研究进展

氧气是哺乳动物机体代谢稳态维持的物质基础,若代谢过程中氧气供给不足,可造成低氧应激。目前,环境低氧、代谢性低氧和携氧细胞功能障碍是造成动物低氧应激的重要成因。目前,低氧对动物机体代谢和组织功能的影响研究主要集中于肺脏、肝脏、消化道、肌肉和乳腺等部位。若处于低氧状态的哺乳动物形成了适应低氧的代谢模式,则可维持其代谢稳态;相反,若动物无法维持低氧状态下的代谢稳态,则会导致机体氧化应激甚至病变。目前,低氧应激在家畜方面的研究主要集中于高原动物代谢适应机制;然而,泌乳期动物机体代谢速率、氧气消耗和自由基水平均较高,但氧在泌乳动物代谢应激形成中的作用及其对泌乳性能的影响,仍有待探索。综述了哺乳动物产生低氧应激的代谢成因与作用结果,旨在探讨哺乳动物低氧应激生物学基础,为进一步从低氧应激调控角度为泌乳动物的健康状况维持提供理论依据。     

低氧诱导因子—１的结构、功能、调节及其与低氧信号转导的关系

在许多类型细胞均发现低氧可诱导低氧诱导因子－１（ＨＩＦ－１）水平的增高,说明存在一个普遍的氧感受和低氧信号转导机制,其中ＨＩＦ－１起着重要的作用。本文综述了ＨＩＦ－１的结构、功能和活性调节及其与低氧信号转导的关系等方面的研究进展。     

低氧反应通路

氧对生命活动的重要性被发现以来,人们对低氧作用的研究,先后经历了由经典低氧反应效应到红细胞生成素（ＥＰＯ）,由ＥＰＯ到低氧诱导因子－１（ＨＩＦ－１）,由ＨＩＦ－１到一系列低氧反应基因,再 到氧感受,历时２００余年。直到２０世纪９０年代,人们才初步勾划出一条由氧感受器一信号转导一效应基因的低氧反应通路的现代轮廓,为进一步研究既提供了重要基础,也提出了诸多关键课题,随着这一通路研究的深入,人们可望在２１世纪到新的理论概括和实际应用。     

低氧诱导因子抑制因子在低氧性肺动脉高压中的作用

目的:研究低氧性肺动脉高压(hypoxic pulmonary hypertension,HPH)形成过程中低氧诱导因子抑制因子(factor inhibiting hypoxia-inducible factor-1,FIH)在肺小动脉的表达变化及在HPH发病中的可能作用。方法:将36名患者分为慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)并肺动脉高压组(pulmonary hypertension,PH)组(PH组)、COPD非PH组(COPD组)、对照组,收集肺组织,观察其肺血管重塑指标,原位杂交法与免疫组织化学法检测肺小动脉壁FIH m RNA和蛋白的表达水平。结果:COPD组患者肺小动脉出现血管重塑,PH组患者肺小动脉重塑更明显(P0.05)。FIH m RNA在各组患者肺小动脉壁的表达无明显差异(P0.05);FIH蛋白在对照组患者肺小动脉壁高表达,COPD组表达降低,PH组表达进一步减少(P0.05)。直线相关分析表明,FIH蛋白与FIH m RNA无相关(P0.05);FIH蛋白与肺小动脉重塑指标、肺动脉收缩压均呈负相关(P0.01)。结论:慢性肺泡性低氧下调患者肺小动脉壁FIH表达,进而参与患者HPH发病。     

低氧信号传导途径与鱼类低氧适应

低氧信号传导途径是从线虫到哺乳动物都十分保守的一个细胞信号传导途径系统,它对于维持后生动物的氧稳态至关重要.低氧诱导因子是该信号传导系统中最为关键的因子.对低氧诱导因子的调控是对低氧信号途径网络进行有效调控的主要方式.由于鱼类生存的水环境溶氧量的变化很大,在长期进化过程中,鱼类演化出适应不同浓度溶氧水环境的物种,并发展出千差万别的低氧适应策略.对鱼类低氧适应策略及其低氧适应机制的研究,对于认识鱼类物种形成的动因和培育耐低氧鱼类新品种具有十分重要的意义.本文在总结低氧信号传导及其调控机制研究进展的基础上,综述了鱼类低氧信号途径、低氧适应策略、低氧信号途径网络调控等方面研究的慨况.     

低氧诱导因子脯氨酰羟化酶与OS－9在大鼠低氧肺动脉高压中的协同作用

目的：研究HIF-1α、PHDs及OS-9的表达变化在低氧性肺动脉高压（HPH）中的作用和意义。方法：SD大鼠随机分5组（n=8）;对照组（C组）和低氧3、7、14和21d组,常压低氧复制HPH大鼠模型。原位杂交、RT-PCR检测mRNA表达,免疫组化、Westernblot检测蛋白质表达。结果：①HIF-1αmRNA对照纽和低氧3d无明显差异,低氧14d后表达明显增高;HIF-1α蛋白质低氧3d组表达明显增高,7d达高峰;②对照组PHD1mRNA呈阳性表达,各低氧组与对照组比较差异不显著,PHD1蛋白质在对照组强阳性表达,低氧14d下降,低氧21d保持较低水平;对照组PHD2mRNA呈阳性表达,低氧3d增高,14d达到高峰,21d维持高水平,其蛋白质表达趋势与mRNA相同;对照组PHD3mRNA和蛋白质表达不明显,低氧3dmRNA明显增高,蛋白质低氧3d明显增高,低氧7d保持高水平,低氧14d和21d下降。③OS-9mRNA在对照组呈强阳性表达,低氧3d后迅速降低,14d达到最低水平;其蛋白质表达趋势与mRNA相同。相关分析表明,肺小动脉壁OS-9蛋白质表达水平与OS-9mRNA呈正相关,与RVHI、mPAP、WA％及LA％呈负相关。结论：HIF-1α、PHDs及OS-9均在大鼠HPH的发病机制中发挥作用。OS-9可能通过增强PHDs的活性来调节HIF-1α的表达,从而在HPH的发生和发展中发挥作用。     

Use of cenograms in mammalian palaeoecology. A critical review

Cenograms are graphic representations of the size distribution of the mammalian species present in a community and are used in palaeoecological studies to obtain information about the environment. Three empirical rules are commonly applied in the interpretation of cenograms. This paper reviews the methodology of cenograms, special attention being paid to those rules. A database of 92 recent faunas and environmental data has been used to explore the relationships between the shape of the cenograms and the environment. A quantitative procedure has been developed to test the validity of the rules from a statistical point of view. The analyses carried out in this paper failed to confirm the alleged relationships between the size distribution of the large mammals and the aridity of the environment and between the size distribution of the small mammals and the temperature. The gap in medium-sized species is related to the vegetation structure, although only in tropical communities.     

Prognostic value and immune cell infiltration of hypoxic phenotype‐related gene signatures in glioblastoma microenvironment

Glioblastoma (GBM) is a malignant intracranial tumour with the highest proportion and lethality. It is characterized by invasiveness and heterogeneity. However, the currently available therapies are not curative. As an essential environmental cue that maintains glioma stem cells, hypoxia is considered the cause of tumour resistance to chemotherapy and radiation. Growing evidence shows that immunotherapy focusing on the tumour microenvironment is an effective treatment for GBM; however, the current clinicopathological features cannot predict the response to immunotherapy and provide accurate guidance for immunotherapy. Based on the ESTIMATE algorithm, GBM cases of The Cancer Genome Atlas (TCGA) data set were classified into high‐ and low‐immune/stromal score groups, and a four‐gene tumour environment‐related model was constructed. This model exhibited good efficiency at forecasting short‐ and long‐term prognosis and could also act as an independent prognostic biomarker. Additionally, this model and four of its genes (CLECL5A, SERPING1, CHI3L1 and C1R) were found to be associated with immune cell infiltration, and further study demonstrated that these four genes might drive the hypoxic phenotype of perinecrotic GBM, which affects hypoxia‐induced glioma stemness. Therefore, these might be important candidates for immunotherapy of GBM and deserve further exploration.     

The pattern of ovulation in the southern African spiny mouse (Acomys spinosissimus)

The pattern of ovulation in mammals is generally considered to be either spontaneous or induced by coitus. The present study aimed to assess the pattern of ovulation in the southern African spiny mice (Acomys spinosissimus). Females were divided into three treatments differing in the degree of contact with a male. Control females had no contact with males, separated females had only chemical, auditory and visual contact with a male as the sexes were separated with wire mesh and paired females had full contact with a vasectomized male and copulations were possible. Each treatment consisted of seven females and the ovarian mass, the number of primary, secondary/tertiary and Graafian follicles as well as presence of corpora lutea were compared between the three treatments. Faecal progestagen metabolite (FPM) concentrations were analyzed for every second day throughout the experiment and they were used to determine luteal phases and oestrous cycles. Corpora lutea were found in both the control and the paired treatment indicating that ovulation also occurred in the absence of coitus. There was also no effect of treatment on ovarian mass or follicle numbers. In contrast, only females in the separated and paired treatments exhibited luteal phases and oestrous cycles. Especially at the beginning of the experiment, FPM concentrations were higher in those two groups than the control. The results indicate that A. spinosissimus appears to ovulate spontaneously, although physical as well as olfactory male cues appear to be of great importance to enhance reproductive efforts of females.     

A search for quantitative trait loci for ovulation rate in cattle

Seventy-seven polymorphic microsatellites were analysed in offspring of three elite sires that were part of the foundation of an experimental population selected for twinning rate at the US Meat Animal Research Center, Clay Center, Nebraska. All females were assessed for ovulation rate by rectal palpation of corpora lutea over 8–10 consecutive oestrous cycles from approximately 12 to 18 months of age, and associations between ovulation rate and sire allele were examined in each of the three sire groups. A preliminary analysis was performed using selectively genotyped daughters of each sire. Markers found significant or approaching significance were also genotyped in all daughters, sons and granddaughters of these sires. A test of marker associations limited to the granddaughter data provided an independent confirmation of marker effect and significance relative to the initial test with daughter data. Putative ovulation rate quantitative trait loci were detected on chromosomes 7 and 23. Marker UWCA20 on chromosome 7 was associated with an effect in excess of one phenotypic standard deviation and accounted for approximately 10% of phenotypic variation ovulation rate. Marker CYP21 (steroid 21-hydroxylase) on chromosome 23 was associated with an effect of slightly less than half a phenotypic standard deviation and accounted for approximately 4% of phenotypic variation.     

低氧预适应增强大鼠海马神经元的耐缺氧能力

本研究对整体大鼠进行了模拟不同海拔高度（3000、5000m）的低氧预适应,然后观察了急性致死性缺氧对这些大鼠海马脑片诱发群锋电位的影响。结果显示,经低氧预适应的大鼠其海马脑片在给予急性缺氧后,CA1区缺氧损伤电位（hypoxic injury potential,HIP）出现时间以及突触前排放（presynaptic volley,PV）消失时间均明显延迟;其中5000m预适应组的延迟程度比3000m组明显。复氧后,PV的恢复率在3000m和5000m低氧预适应组均明显高于对照组。本研究结果提示,整体动物的低氧预适应可以增强离体海马脑片神经元的耐缺氧能力。     

Novel role for the δ-opioid receptor in hypoxic preconditioning in rat retinas

δ-Opioid receptor (DOR) is an oxygen-sensitive protein whose function in the rat retina is unknown. We examined whether DOR is involved in hypoxic preconditioning (HPC)-mediated retinoprotection following intraocular pressure (IOP) elevation. Rats were exposed to intermittent hypoxia (10% oxygen) to induce HPC. Unilateral retinal ischemia/reperfusion injury was induced by elevating IOP to 100 mmHg for 1 h. HPC attenuated the loss of neuronal marker expression and increased pro-apoptotic caspase 3 activity in the IOP retina. Excess superoxide production and 8-iso-prostaglandin F2α accumulation caused by enhanced oxidant protein expression and reduced antioxidant enzyme level after IOP elevation were largely abrogated by HPC. HPC markedly increased the expression of hypoxia-inducible factor-1α (HIF-1α) and DOR, but intravitreal administration of HIF-1α-specific small interfering RNA abrogated the up-regulation of DOR. This suggested that DOR functions downstream of HIF-1α. However, the endogenous content of leucine enkephalin in retinas was not affected by HPC or IOP. Treatment of retinas with the DOR antagonist naltrindole attenuated the HPC-induced protection and activation of extracellular signal-regulated kinase. These results suggest a novel mechanism of HPC-mediated retinoprotection whereby HIF-1α induces the expression of DOR, and DOR-mediated activation of extracellular signal-regulated kinase triggers cellular events that correct the redox imbalance in the post-ischemic retina.     

Validation of SNP associations with bovine ovulation and twinning rate

Previous work identified SNP associations with twinning rate in the US Holstein population and developed a model for genomic prediction. The current study was conducted to assess the association of these SNPs with twinning rate and ovulation rate in a genetically diverse, outbred population selected for twinning and ovulation rate. A total of 18 SNPs that were components of a prediction equation for twinning rate in Holstein cattle were genotyped on 731 animals from the USDA Meat Animal Research Center production efficiency or twinning population. These 731 individuals were sires and dams well represented in the pedigrees of animals from the twinner population, and their genotypes were used in predicting genotypes for animals in the larger population (n = 16 035). Twinning rate and ovulation rate were analyzed in a two‐trait repeated records analysis with marker associations analyzed individually as fixed effects. Criteria for marker validation were effect estimate with a sign consistent with previous estimates and significance at a nominal P < 0.01. Of the 14 SNPs passing quality control assessments, only one was validated. A SNP in the 5′ flanking region of the IGF1 gene, discovered previously in a positional candidate gene analysis, was significantly associated with twinning rate in the USDA twinning population (P < 0.0002). This SNP may have utility in genomic prediction of twinning rate beyond the Holstein population.     

The induction of ovulation in anovulatory goats by oestrous females

Oestrous female Australian cashmere goats were shown to induce ovulation in seasonally anovulatory counterparts. Sixty anovulatory does were exposed to either ovariectomised (OVX) does or oestrogen treated OVX does in isolated groups of ten, with three replicates for each treatment. Ovaries were examined by laparoscopy 5 and 10 days after exposure to the OVX does. Following exposure to untreated OVX does, three of 30 does ovulated within 5 days, one of which re-ovulated before Day 10; one other doe ovulated once 6–10 days after exposure. In contrast, 23 of 30 does exposed to OVX does in induced oestrus ovulated within 5 days of exposure, with 12 re-ovulating before Day 10, the balance lapsing into anovulation. Two other does in this group ovulated once 6–10 days after exposure. The ovulation rate in the does exposed to oestrous OVX does was significantly higher than in the control does that ovulated. The experiment unequivocally shows that oestrous females can induce ovulation in anovulatory does.