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Polymorphic variants of the serotonin receptor, 5-HT1A, and the serotonin transporter, 5-HTTLPR, and adverse pregnancy outcomes: A pilot study 5-羟色胺受体5-HT1A和5-羟色胺转运体5-HTTLPR的多态性变异与不良妊娠结局:一项初步研究
Pub Date : 2015-07-01 DOI: 10.1016/j.jrhm.2015.06.004
Hamutal Taube , Aharon Tevet , Gheona Altarescu , Arnon Samueloff , Sorina Grisaru-Granovsky

Background/aims

Antenatal depression may have adverse effects on pregnancy outcomes such as preterm birth (PTB) and small-for-gestational-age neonates. Serotonin as a neurotransmitter is intimately related to stress and depression. The purpose of this study was to assess variants of the serotonin receptor (5-HT1A) gene and serotonin transporter promoter (5-HTTLPR) gene as potentially directly involved in adverse pregnancy outcomes (APOs), especially PTB.

Methods

A pilot case-control study over two years identifying 78 women delivered at <35 weeks gestational age (PTB) and 265 women with uncomplicated singleton term delivery who were evaluated for APO and early pregnancy loss (EPL) in a division for maternal and fetal medicine in a single tertiary center.

Results

Women with the s/s serotonin transporter 5-HTTLPR genotype experienced significantly more EPLs but there was no significant association between serotonin polymorphisms and preterm birth.

Conclusion

Two serotonin gene polymorphisms, known to be associated with depression, are hereby shown to be associated with APO. EPL, but not preterm birth, is significantly linked to an s/s serotonin transporter 5-HTTLPR genotype.

背景/目的产前抑郁可能对妊娠结局产生不良影响,如早产(PTB)和胎龄小的新生儿。血清素作为一种神经递质与压力和抑郁密切相关。本研究的目的是评估5-羟色胺受体(5-HT1A)基因和5-羟色胺转运子启动子(5-HTTLPR)基因的变异是否可能直接参与不良妊娠结局(APOs),特别是PTB。方法一项为期两年的试点病例对照研究,选取78名35周孕龄(PTB)分娩的妇女和265名无并发症单胎足月分娩的妇女,在单一第三中心的母婴医学部门评估APO和早期妊娠丢失(EPL)。结果5 /s 5-羟色胺转运体5-HTTLPR基因型女性的epl显著增加,但5-羟色胺多态性与早产之间无显著相关性。结论两种已知与抑郁症相关的血清素基因多态性与APO相关。EPL与s/s血清素转运体5-HTTLPR基因型显著相关,但与早产无关。
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引用次数: 0
Association of organochlorine pesticides and risk of epithelial ovarian cancer: A case control study 有机氯农药与上皮性卵巢癌风险的关系:一项病例对照研究
Pub Date : 2015-07-01 DOI: 10.1016/j.jrhm.2015.01.006
Tusha Sharma , Basu Dev Banerjee , Darshana Mazumdar , Vipin Tyagi , Gaurav Thakur , Kiran Guleria , Rafat S. Ahmed , Ashok Kumar Tripathi

Background/aims

Organochlorine pesticides (OCPs) belongs to the class of hydrocarbons characterize by its cyclic structure. Due to their persistence nature OCP gets accumulated in the food chain and cause possible adverse health effects specifically various hormone mediated disorders. Ovarian cancer is also one of the hormone dependant cancer and begins with the transformation of cells that comprises the ovaries including surface epithelial, germ cells, etc. It has been suggested that endocrine disruption, exposure to xenobiotic and subsequent oxidative stress may antedate ovarian cancer and contribute to its pathogenesis. However, no report regarding any association of OCP level with etiology of epithelial ovarian cancer is so far available among North Indian population.

Methods

A total of 120 subjects were included in this case control study, consisting of 60 histological proven cases of epithelial ovarian cancer and 60 controls subjects. Quantification of OCP levels was done by Perkin Elmer Gas Chromatograph (GC) equipped with 63Ni selective Electron Capture Detector.

Results

Levels of β-HCH, endosulfan I, p'p'-DDT, p'p'-DDE and heptachlor were found significantly high in cases of epithelial ovarian cancer as compare to control. A significant association was also observed between higher levels of β-HCH and heptachlor and EOC with odds ratio of 2.76 and 2.97 respectively.

Conclusion

Results indicate the plausible role of OCPs with the pathogenesis of epithelial ovarian cancer among north Indian population. Moreover, it is one of the first report suggesting significant level of heptachlor among north Indian women population with epithelial ovarian cancer.

背景/目的有机氯农药(OCPs)是一类以其环结构为特征的碳氢化合物。由于其持久性,OCP在食物链中积累,并可能对健康造成不利影响,特别是各种激素介导的疾病。卵巢癌也是一种激素依赖性癌症,开始于卵巢细胞的转化,包括表面上皮细胞、生殖细胞等。有研究表明,内分泌紊乱、暴露于异种生物和随后的氧化应激可能早于卵巢癌并有助于其发病。然而,到目前为止,在北印度人群中还没有关于OCP水平与上皮性卵巢癌病因的任何关联的报告。方法本研究共纳入120例病例对照研究,其中组织学证实的上皮性卵巢癌病例60例,对照组60例。OCP含量定量采用Perkin Elmer气相色谱仪(GC),配备63Ni选择性电子捕获检测器。结果上皮性卵巢癌中β-六氯环己烷、硫丹I、p' '-DDT、p' '-DDE和七氯的水平显著高于对照组。高水平的β-HCH与七氯和EOC之间也存在显著的相关性,比值比分别为2.76和2.97。结论OCPs在印度北部人群上皮性卵巢癌发病机制中可能起一定作用。此外,这是第一个报告表明显著水平的七氯在北印度妇女人群上皮性卵巢癌。
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引用次数: 1
Radiation induced oxidative stress and its toxicity in testes of mice and their prevention by Tinospora cordifolia extract 辐射诱导小鼠睾丸氧化应激及其毒性及堇青花提取物的预防作用
Pub Date : 2015-07-01 DOI: 10.1016/j.jrhm.2015.01.005
Priyanka Sharma , Jyoti Parmar , Preeti Verma , P.K. Goyal

Background

Reproductive dysfunctions induced by various environmental toxicants are the prime concern in the today's changing global scenario. Living systems are constantly exposed to ionizing radiation that cause cellular as well as genetic alterations leading to mutations and cell death. To evaluate the deleterious effects of low dose of gamma radiation on testicular tissue and their possible inhibition by Tinospora cordifolia root extract (TCE).

Methods

One group of Swiss albino mice was exposed to 2.5 Gy gamma radiation to serve as the irradiated control, while the other group received TCE (75 mg/kg b. wt./day) orally for 5 consecutive days half an hour before irradiation to serve as experimental.

Results

Irradiated animals experienced more severe testicular histopathological lesions and a considerable depletion in different spermatogenic cell counts as compared to that of normal animal. Furthermore, TCE pretreatment effectively prevented radiation-induced alterations in body weight, tissue weight, weight index, tubular diameters and anti oxidative parameter viz. lipid peroxidation, glutathione and catalase activity in testes and restored almost a normal structure of testes.

Conclusion

T. cordifolia root extract can be potentially used as an effective radio-protector against radiation induced testicular injuries in mammals.

在当今不断变化的全球环境中,各种环境毒物引起的生殖功能障碍是人们最关心的问题。生命系统不断暴露在电离辐射下,导致细胞和基因改变,导致突变和细胞死亡。目的探讨低剂量伽玛辐射对睾丸组织的有害影响及堇青花根提取物(TCE)的抑制作用。方法采用2.5 Gy γ射线照射瑞士白化病小鼠作为照射对照,另一组小鼠在照射前半小时口服TCE (75 mg/kg b. wt./d),连续5 d作为实验。结果与正常动物相比,辐射动物睾丸组织病理病变更严重,不同生精细胞计数明显减少。此外,TCE预处理能有效地预防辐射引起的睾丸体重、组织重量、体重指数、管径及抗氧化指标(脂质过氧化、谷胱甘肽和过氧化氢酶活性)的改变,使睾丸结构基本恢复正常。堇叶提取物可作为一种有效的辐射保护剂,用于防止哺乳动物睾丸受到辐射损伤。
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引用次数: 3
Women and the burden of human reproduction: An evolutionary perspective 妇女和人类生育的负担:一个进化的观点
Pub Date : 2015-07-01 DOI: 10.1016/j.jrhm.2015.06.002
Mahmoud F. Fathalla

Women carry a heavy and disproportionate burden in human reproduction. Biological, medical, and social determinants account for this burden. An evolutionary perspective can shed additional light. For the evolution of our brain, the human female took major risks to her health and life, to nourish and develop this spectacular brain in utero, to deliver its large size safely through a relatively narrow and irregular bipedal pelvis, and to care for its development for a long time after birth. It is high time for this human brain to pay women back in the currency of science, and to ease their sexual and reproductive health burden.

妇女在人类生育方面承担着沉重而不成比例的负担。生物、医学和社会决定因素是造成这一负担的原因。进化的观点可以提供更多的启示。为了我们大脑的进化,人类女性在她的健康和生命上冒了很大的风险,在子宫里滋养和发展这个壮观的大脑,通过一个相对狭窄和不规则的两足骨盆安全地分娩它的大尺寸,并在出生后很长一段时间内照顾它的发育。现在是人类大脑用科学的货币回报妇女,减轻她们的性健康和生殖健康负担的时候了。
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引用次数: 4
Transgenerational epigenetic inheritance: Emerging concepts and future prospects 跨代表观遗传:新兴概念和未来展望
Pub Date : 2015-07-01 DOI: 10.1016/j.jrhm.2015.06.001
Abhay Sharma

Evidence for transgenerational epigenetic inheritance has accumulated in recent years. However, the perceived implausibilities of epigenetic memory survival across chromatin remodeling and reprogramming, and phenotypic information transfer from soma to germline have caused skepticism about its existence, especially in mammals. Importantly, these supposed fundamental impediments seem to be disappearing with recent advances. Evolutionary significance of epigenetic inheritance is another area of debate. Notably, the idea that induced variations may play a role in evolution is gaining ground with newer analysis. Overall, emerging concepts are increasingly calling for integration of nongenetic inheritance in the contemporary evolutionary theory that does not completely explain heritability of complex traits and diseases. Interestingly, a conceptual framework of “evolutionary transgenerational systems biology” has recently been proposed to integrate epigenetics and physiology with inheritance and evolution. A proof of concept analysis is warranted to test the future prospects of this unified theory of biology.

近年来,跨代表观遗传的证据越来越多。然而,表观遗传记忆在染色质重塑和重编程中的生存以及从体细胞到种系的表型信息传递的不真实性引起了对其存在的怀疑,特别是在哺乳动物中。重要的是,随着最近的进步,这些所谓的基本障碍似乎正在消失。表观遗传的进化意义是另一个有争议的领域。值得注意的是,诱导变异可能在进化中发挥作用的观点随着新的分析而逐渐流行起来。总的来说,新兴的概念越来越多地要求将非基因遗传整合到不能完全解释复杂性状和疾病的遗传能力的当代进化理论中。有趣的是,最近提出了一个“进化跨代系统生物学”的概念框架,将表观遗传学和生理学与遗传和进化结合起来。为了检验这一生物学统一理论的未来前景,有必要进行概念分析的证明。
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引用次数: 6
Reproduction and nutriment–nurture crosstalk: epigenetic perspectives 生殖和营养-滋养相声:表观遗传学的观点
Pub Date : 2015-07-01 DOI: 10.1016/j.jrhm.2015.07.002
Varij Nayan, Suneel Kumar Onteru, Dheer Singh

Epigenetics refers to the acquisition and maintenance of heritable states of gene expression that occurs above the level of genetics through alterations in chromatin structure and accessibility. The field of epigenetics has moved much ahead from an emerging science and is growing at a faster pace, as there is increased realization about nutriment and nurture–epigenetic–phenotype relationship. Scientific studies concerning epigenetic changes in the genome in a systematic and genome-wide way provide clinching evidence for epigenetic interactions of environmental and lifestyle factors with genes and determine the reproductive outcomes and health. The epigenetic mechanisms are traditionally studied as DNA methylation, histone modifications, ATP-dependent chromatin remodeling, and noncoding RNA-mediated regulation. In the present review, we have presented an overview of the epigenetics evolved from the interaction and confluence of reproduction and nutrient environment. Besides, our experience with DNA methylation and chromatin modification of the cytochrome P450 aromatase (CYP19) gene is also presented. Understanding the emergence of paradigm shift in the reproductive epigenetics appears important as it will open up new vistas for viewing the impact of environment and dietary components on regulation of gene expression concerning the reproductive events and health conditions.

表观遗传学是指通过改变染色质结构和可及性来获得和维持遗传水平以上的基因表达的可遗传状态。表观遗传学领域已经从一门新兴的科学向前迈进了很多,并且正在以更快的速度发展,因为人们对营养和培养-表观遗传-表型关系的认识越来越高。对基因组表观遗传变化的系统和全基因组的科学研究为环境和生活方式因素与基因的表观遗传相互作用提供了确凿的证据,并决定了生殖结果和健康。表观遗传机制传统上被研究为DNA甲基化、组蛋白修饰、atp依赖性染色质重塑和非编码rna介导的调控。本文综述了生殖与营养环境相互作用和融合的表观遗传学研究进展。此外,我们的DNA甲基化和染色质修饰的细胞色素P450芳香化酶(CYP19)基因也提出了经验。理解生殖表观遗传学中范式转变的出现是很重要的,因为它将为观察环境和饮食成分对与生殖事件和健康状况有关的基因表达调控的影响开辟新的前景。
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引用次数: 5
Transgenerational epigenetic inheritance: Where do we stand today? 跨代表观遗传:我们今天的研究进展如何?
Pub Date : 2015-07-01 DOI: 10.1016/j.jrhm.2015.01.007
M.A. Bhat, G. Anupa, D. Ghosh
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引用次数: 2
Gel-free proteomics reveals neoplastic potential in endometrium of infertile patients with stage IV ovarian endometriosis 无凝胶蛋白质组学揭示了不孕患者子宫内膜的肿瘤潜力与期卵巢子宫内膜异位症
Pub Date : 2015-07-01 DOI: 10.1016/j.jrhm.2015.06.003
D. Ghosh , S. Nagpal , M.A. Bhat , G. Anupa , A. Srivastava , J.B. Sharma , Jayasree Sengupta

Background/aims

Indirect evidence suggests that eutopic endometrium of women suffering from endometriosis shows differential physiological characteristics as compared to normal endometrium in unaffected women. We have evaluated this issue by using hypothesis-neutral proteomics approach.

Methods

In order to examine the differential display of steady state expressed proteins between control endometrium from infertile women with no detectable endometriosis disease and that from infertile women with proven stage IV ovarian endometrioma, a large-scale gel-free 2D proteomic analysis, followed by QTOF LC-MS system and immunohistochemistry for subsequent validation was employed in the present study.

Results

We could identify several dysregulated endometrial proteins in women suffering from stage IV ovarian endometriosis, which included proteins involved in regulating cellular redox states, cellular signaling, cytoskeletal functions, stress response, apoptosis, salt-water balance, and heme metabolism. Additionally, an overt indication of telomere maintenance and that of neoplastic potential of eutopic endometrium of infertile women with stage IV ovarian endometriosis was observed in post hoc bioinformatics-based analysis. This was further substantiated by consistent high immunopositive expression of four cancer-associated specific proteins (annexin A2, HSP90, PDGFRa, and Tubulin-a) in endometrium of infertile patients with stage IV ovarian endometriosis.

Conclusion

It appears highly plausible that endometrial cells in women with stage IV ovarian endometriosis cannot adequately support embryo implantation process due to innate molecular inadequacies. Furthermore, these cells with molecular defects on their reflux into pelvic peritoneal niche may result in endometriotic lesion. Most importantly, pathognomonic characteristics showing marked indication of neoplastic potential in endometrium of infertile patients with stage IV ovarian endometriosis bear a possibility of inducement of oncogenic transformation especially in the high-risk population in the course of endometriosis disease progression.

背景/目的直接证据表明,患有子宫内膜异位症的女性的异位子宫内膜与未受影响的女性的正常子宫内膜表现出不同的生理特征。我们使用假设中性的蛋白质组学方法对这个问题进行了评估。方法为了研究未检测到子宫内膜异位症的不孕妇女的对照子宫内膜与已确诊的IV期卵巢子宫内膜异位症的不孕妇女的对照子宫内膜稳态表达蛋白的差异,本研究采用大规模无凝胶2D蛋白质组学分析,然后采用QTOF LC-MS系统和免疫组织化学进行后续验证。结果在卵巢子宫内膜异位症患者中发现了几种异常的子宫内膜蛋白,包括调节细胞氧化还原状态、细胞信号传导、细胞骨架功能、应激反应、细胞凋亡、盐水平衡和血红素代谢的蛋白。此外,在术后基于生物信息学的分析中,我们观察到伴有IV期卵巢子宫内膜异位症的不孕妇女的端粒维持和异位子宫内膜肿瘤潜力的明显迹象。四种癌症相关特异性蛋白(膜联蛋白A2、HSP90、PDGFRa和微管蛋白-a)在伴有IV期卵巢子宫内膜异位症的不孕症患者的子宫内膜中一致的高免疫阳性表达进一步证实了这一点。结论卵巢IV期子宫内膜异位症患者的子宫内膜细胞可能由于先天的分子缺陷而不能充分支持胚胎着床过程。此外,这些细胞在返流到盆腔腹膜生态位时存在分子缺陷,可能导致子宫内膜异位病变。最重要的是,不孕的IV期卵巢子宫内膜异位症患者的子宫内膜有明显的肿瘤潜能的病理特征,特别是在子宫内膜异位症疾病进展过程中的高危人群中,有诱发癌性转化的可能。
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引用次数: 9
The effect of IBMX and hormones on gene expression by rat Sertoli cells IBMX和激素对大鼠支持细胞基因表达的影响
Pub Date : 2015-01-01 DOI: 10.1016/j.jrhm.2014.12.001
Indrashis Bhattacharya , Mukkesh Gautam , Subeer S. Majumdar

Background

Sertoli cells (Sc) regulate spermatogenesis under the control of FSH and testosterone (T). Functional maturation of Sc for supporting the spermatogenic onset during pubertal development is prerequisite for male fertility. However, the effect of hormone driven maturational changes in Sc is not well known.

Objectives and experimental model

In this present study we have compared hormone induced gene expression of immature and mature Sc isolated from neonatal (9-days old) and prepubertal (18-days-old) rat testes, respectively, to investigate the developmental difference of hormone responsiveness of Sc during postnatal maturation as well as influence of 3-isobutyl-1-methylxanthine (IBMX), a nonspecific inhibitor of phosphodiesterase in primary culture of Sc.

Results and conclusion

Our results suggested that FSH responsiveness of Sc obtained from 18-days-old rats were more prominent in terms of augmentation of lactate, cAMP and gene transcription as compared to Sc from 9-days of age. Our result also indicated that although the use of IBMX in primary culture of Sc generates a better readout in terms of FSH induced cAMP response, the presence of such pharmacological agent mellows down FSH stimulated gene expression profile. Our data indicated further that immature Sc are capable of differentiating in vitro if cultured with continuous supplementation of FSH and T (in combination). Taken together, we also concluded that for accurate evaluation of the modulation of gene expression by hormones, use of IBMX should be avoided in primary cultures of Sc.

支持细胞(Sc)在卵泡刺激素(FSH)和睾酮(T)的控制下调节精子发生。Sc在青春期发育过程中支持精子发生的功能成熟是男性生育能力的先决条件。然而,激素驱动Sc成熟变化的作用尚不清楚。在本研究中,我们比较了从新生大鼠(9日龄)和青春期前大鼠(18日龄)睾丸中分离的未成熟Sc和成熟Sc的激素诱导基因表达,以探讨Sc在出生后成熟过程中激素反应性的发育差异以及3-异丁基-1-甲基黄嘌呤(IBMX)的影响。结果和结论我们的研究结果表明,与9日龄的Sc相比,18日龄大鼠获得的Sc在乳酸、cAMP和基因转录方面的FSH反应性更为突出。我们的结果还表明,尽管在Sc原代培养中使用IBMX在FSH诱导的cAMP反应方面产生了更好的结果,但这种药理学剂的存在缓和了FSH刺激的基因表达谱。我们的数据进一步表明,如果持续补充FSH和T(联合)培养,未成熟的Sc能够在体外分化。综上所述,我们还得出结论,为了准确评估激素对基因表达的调节作用,应避免在Sc原代培养中使用IBMX。
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引用次数: 1
Physiological balance between fVEGF and sVEGFR1 is maintained within ovarian follicles in normoresponder women irrespective of GnRH-agonist and GnRH-antagonist protocols 无论gnrh激动剂和gnrh拮抗剂方案如何,正常反应的女性卵巢卵泡内维持fVEGF和sVEGFR1的生理平衡
Pub Date : 2015-01-01 DOI: 10.1016/j.jrhm.2014.10.001
Neena Malhotra , Asmita Patil , Nalin Mehta , Harpal Rana , Jayasree Sengupta , Debabrata Ghosh

The hypothesis that there exists a differential association between total free VEGF (fVEGF) and soluble VEGF-receptor1 (sVEGFR1) in follicular fluid obtained from GnRH-agonist (GnRH-a) versus GnRH-antagonist (GnRH-ant) protocols was examined. It was observed that: (i) concentration of total fVEGF in follicular fluid retrieved from GnRH-ant group was higher than that in GnRH-a group, (ii) it was three-times higher than that of VEGF-A alone as reported in the previous study, and (iii) follicular concentration of sVEGFR1 showed no significant difference between two groups. Finally, our hypothesis that ratios of follicular sVEGFR to fVEGF might show differential profiles between two protocols was not found tenable. We conclude that the physiological balance between sVEGFR1 and total fVEGF is maintained within a ratio of 2–3 in ovarian follicles in normoresponder women irrespective of GnRH-a and GnRH-ant protocols.

研究人员检验了gnrh激动剂(GnRH-a)和gnrh拮抗剂(GnRH-ant)获得的卵泡液中总游离VEGF (fVEGF)和可溶性VEGF受体1 (sVEGFR1)之间存在差异的假设。我们观察到:(i) GnRH-ant组提取的卵泡液中总fVEGF浓度高于GnRH-a组,(ii)比既往研究报道的单独VEGF-A组高3倍,(iii)两组间滤泡中sVEGFR1浓度无显著差异。最后,我们关于卵泡sVEGFR与fVEGF比值在两种方案中可能表现出差异的假设是站不住脚的。我们得出结论,无论GnRH-a和GnRH-ant方案如何,在正常反应的女性卵巢卵泡中,sVEGFR1和总fVEGF之间的生理平衡维持在2-3的比例。
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引用次数: 1
期刊
Journal of reproductive health and medicine
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