Journal of reproductive health and medicine最新文献

英文中文

Nuclear receptor peroxisomal proliferators activated receptors-gamma ligands decrease histone acetylation and attenuate CYP19 gene expression by chromatin remodeling in buffalo (Bubalis bubalis) granulosa cells 核受体过氧化物酶体增殖体激活受体- γ配体通过水牛颗粒细胞染色质重塑降低组蛋白乙酰化并减弱CYP19基因表达

Journal of reproductive health and medicine

Pub Date : 2015-01-01 DOI: 10.1016/j.jrhm.2014.09.002

Isha Sharma, Dheer Singh

Objective

Role of peroxisomal proliferator activated receptors-gamma (PPARγ) in regulating fertility establishes it as novel signal for the integration of energy balance and reproduction. PPARγ ligands are known to down regulate CYP19 gene expression, a candidate gene encoding rate-limiting enzyme aromatase involved in estradiol-17β biosynthesis. It has been well established that CYP19 gene is regulated epigenetically during folliculogenesis and luteinization. In the present study, we investigated if PPARγ ligands epigenetically regulate CYP19 gene.

Methods

The total acetylation of histone H3 (K9/14) and difference in enrichment of acetylated histone H3 (K9/14) on CYP19 gene promoter were analyzed by western analysis and ChIP assay, respectively.

Results

Result showed that acetylated histone H3 (K9/14) is down-regulated in granulosa cells treated with PPARγ ligands, whereas its expression was reversed when cells were treated with PPARγ antagonist. To validate further, analysis of histone modification under basal and treated conditions using a ChIP assay revealed that the CYP19 gene proximal promoter (PII, known to be ovary-specific promoter) was 450 and 550 fold more enriched with acetylated histone H3 (K9/14) in control and antagonist (GW9662) treated cells, respectively, than the ligand treated cells. The present study demonstrated that CYP19 gene proximal promoter (PII) was more accessible to transcription in control than treated cells.

Conclusion

In conclusion, the present findings provide a novel mechanistic insight into nuclear receptor PPARγ mediated decrease in acetylated histone H3 (K9/14) which in turn remodel chromatin through histone modification and regulate key steroidogenic gene in buffalo granulosa cells.

目的研究过氧化物酶体增殖物激活受体γ (PPARγ)在生殖调节中的作用，使其成为能量平衡与生殖一体化的新信号。已知PPARγ配体可以下调CYP19基因的表达，CYP19是一种候选基因，编码参与雌二醇-17β生物合成的限速酶芳香化酶。CYP19基因在卵泡发生和黄体生成过程中受表观遗传调控。在本研究中，我们研究了PPARγ配体是否通过表观遗传调控CYP19基因。方法采用western分析法和ChIP法分别分析组蛋白H3 (K9/14)的总乙酰化程度和CYP19基因启动子上乙酰化组蛋白H3 (K9/14)富集程度的差异。结果结果显示，乙酰化组蛋白H3 (K9/14)在PPARγ配体处理的颗粒细胞中表达下调，而在PPARγ拮抗剂处理的颗粒细胞中表达逆转。为了进一步验证，在基础和处理条件下使用ChIP分析组蛋白修饰显示，在对照和拮抗剂(GW9662)处理的细胞中，CYP19基因近端启动子(PII，已知是卵巢特异性启动子)的乙酰化组蛋白H3 (K9/14)含量分别比配体处理的细胞高450倍和550倍。本研究表明CYP19基因近端启动子(PII)在对照细胞中比处理细胞更容易转录。结论核受体PPARγ介导乙酰化组蛋白H3 (K9/14)的减少，从而通过组蛋白修饰改造染色质，调控关键的类固醇基因，为水牛颗粒细胞乙酰化组蛋白H3 (K9/14)的减少提供了新的机制。

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引用次数: 0

Tumor necrosis factor alpha promoter polymorphism studies in pregnant women 孕妇肿瘤坏死因子α启动子多态性研究

Journal of reproductive health and medicine

Pub Date : 2015-01-01 DOI: 10.1016/j.jrhm.2015.01.001

Imran Ali Khan , Vasundhara Kamineni , Subhadra Poornima , Parveen Jahan , Qurratulain Hasan , Pragna Rao

Aims

The aim of this study was to explore the possible association between the −850 C/T polymorphism in the tumor necrosis factor alpha (TNF-α) gene promoter, and pregnancy-associated diseases such as gestational diabetes mellitus (GDM) and preeclampsia (PE), in south Indian women. GDM and PE are common complications that occur during pregnancy and are the leading causes of perinatal mortality. To date, the mechanisms that initiate GDM and PE in humans have remained elusive.

Methods

This prospective case-control study was carried out with 505 pregnant women: 140 women had GDM, and 105 with PE. Remaining 260 women were age- and frequency-matched controls. TNF-α (–C850T) genotyping was determined by polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) analysis.

Result

We found no statistically significant difference in the genotypic and allelic distribution between GDM women and controls (for CT + TT vs. CC, χ² = 0.3919; p = 0.61; Odds Ratio (OR) = 0.76 (95% CI: 0.203–1.876)). No significant differences was observed in the allele and genotype frequency between PE women and controls (for CT + TT vs. CC, p = 0.31; OR = 0.55 (95% CI: 0.171–1.784); T vs. C, p = 0.71; OR = 0.94 (95% CI: 0.680–1.3)).

Conclusion

From our results, we conclude that the (–C850T) promoter polymorphism has no role in the propensity of pregnant women from south Indian populations to develop GDM or PE.

目的本研究的目的是探讨南印度妇女肿瘤坏死因子α (TNF-α)基因启动子−850 C/T多态性与妊娠相关疾病(如妊娠糖尿病(GDM)和先兆子痫(PE))之间的可能关联。GDM和PE是妊娠期间常见的并发症，也是围产期死亡的主要原因。迄今为止，在人类中引发GDM和PE的机制仍然难以捉摸。方法本前瞻性病例对照研究纳入505例孕妇，其中GDM 140例，PE 105例。其余260名女性作为年龄和频率匹配的对照组。采用聚合酶链反应限制性片段长度多态性(PCR-RFLP)分析TNF-α (-C850T)基因分型。结果GDM女性与对照组基因型及等位基因分布差异无统计学意义(CT + TT vs. CC， χ2 = 0.3919;p = 0.61;优势比(OR) = 0.76 (95% CI: 0.203-1.876)。PE女性与对照组的等位基因和基因型频率无显著差异(CT + TT vs. CC, p = 0.31;Or = 0.55 (95% ci: 0.171-1.784);T vs. C, p = 0.71;Or = 0.94 (95% ci: 0.680-1.3))。结论(-C850T)启动子多态性与印度南部孕妇患GDM或PE的倾向无关。

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引用次数: 17

Phenotypic expression and polymorphism of Glutathione S Transferase gene in materno-fetal dyads with idiopathic fetal growth restriction 特发性胎儿生长受限母胎双体谷胱甘肽S转移酶基因的表型表达与多态性

Journal of reproductive health and medicine

Pub Date : 2015-01-01 DOI: 10.1016/j.jrhm.2015.01.002

Nilesh Chandra , Mohit Mehndiratta , B.D. Banerjee , K. Guleria , A.K. Tripathi

Introduction

Incidence of fetal growth restriction (FGR) in India is quite high, and FGR has been found to be associated with various non-infectious diseases including coronary artery disease, diabetes mellitus and metabolic syndrome. Moreover, 40% of FGR is termed idiopathic (IFGR) for which cause is not known. Oxidative stress, which is postulated to have a role in FGR, is modulated by polymorphism of antioxidant genes. This study aims to examine association of GST polymorphism and enzymatic activity with incidence of FGR.

Materials and methods

150 unrelated live births participated as dyads (mother and neonate). 75 consecutive IFGR materno-fetal dyads (referred subsequently as IFGR mother and IFGR neonate) were recruited as cases. Polymorphic analysis of GSTT1 and GSTM1 were carried out by multiplex PCR. Glutathione-S-transferase activity in serum was measured using 1-chloro-2, 4-dinitrobenzene (CDNB) as substrate.

Results

Incidence of GSTT1 null type is significantly higher in IFGR fetus and their mothers (p < 0.01). Incidence of GSTM1 null type is significantly higher in IFGR fetus (p = 0.001). GST activity levels in mothers giving birth to IFGR babies was about 50% of the values found in the control group (p < 0.001). The GST activity levels in control group was found to be 50% higher than the FGR babies (p = 0.001).

Conclusion

Our results show that there is definite association between polymorphism of GST genes and incidence of IFGR. Simultaneously, our study also found a correlation between maternal GST activity and fetal weight.

胎儿生长受限(FGR)在印度的发病率相当高，FGR已被发现与各种非传染性疾病，包括冠状动脉疾病、糖尿病和代谢综合征有关。此外，40%的FGR被称为特发性(IFGR)，其原因尚不清楚。氧化应激被认为在FGR中起作用，它是由抗氧化基因的多态性调节的。本研究旨在探讨GST多态性和酶活性与FGR发病率的关系。材料与方法150例无血缘关系的活产婴儿作为双联体(母亲和新生儿)参与研究。连续招募了75例IFGR母胎双胎(随后称为IFGR母亲和IFGR新生儿)作为病例。采用多重PCR对GSTT1和GSTM1进行多态性分析。以1-氯- 2,4 -二硝基苯(CDNB)为底物测定血清谷胱甘肽- s转移酶活性。结果GSTT1零型在IFGR胎儿及其母亲中的发生率显著高于对照组(p <0.01)。GSTM1零型在IFGR胎儿中的发生率显著高于胎儿(p = 0.001)。生下IFGR婴儿的母亲的GST活性水平约为对照组的50% (p <0.001)。对照组GST活性水平比FGR组高50% (p = 0.001)。结论GST基因多态性与IFGR发病率之间存在一定的相关性。同时，我们的研究也发现了母体GST活性与胎儿体重之间的相关性。

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引用次数: 2

Oxygen and glucose dependent viability of HLA-G positive and negative trophoblasts using ACH-3P cells as first trimester trophoblast-derived cell model 以ACH-3P细胞作为妊娠早期滋养层细胞来源的细胞模型，观察HLA-G阳性和阴性滋养层细胞的氧和葡萄糖依赖性活力

Journal of reproductive health and medicine

Pub Date : 2015-01-01 DOI: 10.1016/j.jrhm.2015.01.003

Julia D. Fröhlich , Gernot Desoye , Julia König , Berthold Huppertz

Aims

During pregnancy HLA-G negative proliferative trophoblasts at the tips of anchoring villi form cell columns from which HLA-G positive extravillous trophoblasts invade maternal tissues. During the first trimester of pregnancy an oxygen gradient ranges from placental low to decidual high oxygen, which may have a differential impact on survival of the two trophoblast subpopulations. Moreover, diabetes-associated hyperglycemia may also influence trophoblast proliferation.

Methods

ACH-3P cells were separated by magnetic beads into HLA-G positive and negative cells and checked by PCR and Western blotting. Cell cultures were performed under varying oxygen and glucose concentrations. Numbers of viable and dead cells were assessed and used to calculate proliferation rates.

Results

After separation, HLA-G positive and negative first trimester trophoblast-derived ACH-3P cells exhibit fewer viable cells under hyperglycemia at 2.5% and 8% oxygen, while at 21% oxygen no viable cells were detectable. Cell numbers of HLA-G negative cells were higher compared to HLA-G positive cells at 2.5% and 8% oxygen, while there were significantly less cells at 8% compared to 2.5% only in HLA-G positive cells.

Conclusion

We conclude that the separated cell types are sensitive to both oxygen and glucose independent from each other. Furthermore, oxygen may be one regulator to reduce proliferation of invading HLA-G positive trophoblasts, while alterations in the oxygen gradient early in pregnancy may have deleterious effects on the number of invading extravillous trophoblasts.

目的:在妊娠期间，锚定绒毛顶端的HLA-G阴性增殖性滋养细胞形成细胞柱，HLA-G阳性的胞外滋养细胞由此侵入母体组织。在怀孕的前三个月，氧梯度范围从胎盘低到蜕膜高，这可能对两个滋养细胞亚群的生存有不同的影响。此外，糖尿病相关的高血糖也可能影响滋养细胞的增殖。方法采用磁珠法将sacach - 3p细胞分离为HLA-G阳性细胞和阴性细胞，采用PCR和Western blotting检测。细胞培养在不同的氧气和葡萄糖浓度下进行。评估活细胞和死细胞的数量，并用于计算增殖率。结果分离后，HLA-G阳性和阴性的早期滋养细胞来源的ACH-3P细胞在2.5%和8%氧气下高血糖时活性细胞较少，而在21%氧气下未检测到活细胞。在2.5%和8%氧气条件下，HLA-G阴性细胞的细胞数高于HLA-G阳性细胞，而在8%氧气条件下，HLA-G阳性细胞的细胞数明显少于2.5%氧气条件下的细胞数。结论分离后的细胞类型对氧和葡萄糖均具有独立的敏感性。此外，氧气可能是减少入侵HLA-G阳性滋养层细胞增殖的一种调节因子，而妊娠早期氧气梯度的改变可能对入侵的外滋养层细胞数量产生有害影响。

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引用次数: 3

Why does human chorionic gonadotropin have such a broad regulatory roles in the body and are they totally unexpected? 为什么人绒毛膜促性腺激素在体内具有如此广泛的调节作用，它们是完全出乎意料的吗?

Journal of reproductive health and medicine

Pub Date : 2015-01-01 DOI: 10.1016/j.jrhm.2014.09.001

C.V. Rao, Carlo Ticconi

引用次数: 4

Herbal remedies and traditional medicines in reproductive health care practices and their clinical evaluation 生殖保健实践中的草药和传统药物及其临床评价

Journal of reproductive health and medicine

Pub Date : 2015-01-01 DOI: 10.1016/j.jrhm.2015.01.004

Ranjit Roy Chaudhury

引用次数: 7

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Journal of reproductive health and medicine

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