不良孕产夫妇着丝粒-动粒复合体的细胞遗传学研究

为研究不良孕产夫妇染色体着丝粒-动粒复合体(centromerekinetochorecomplex,CKC)变异与不良孕产的相关性,探索不良孕产中非整倍体形成的细胞遗传学基础,应用改良的着丝粒点-核仁组织区(Cd-NOR)同步银染技术,分别对53对不明原因的不良孕产夫妇和57对已生育正常儿的正常夫妇外周血淋巴细胞染色体CKC变异类型及频率进行研究和分析.结果发现,不良孕产夫妇其小Cd、Cd消失、Cd迟滞和Cd-NOR融合频率均较正常对照组明显增高,两者相比有显著性差异(P＜0.05).CKC变异频率增高可能是导致不良孕产非整倍体形成的主要原因之一。 Abstract:To search the cytogenctic mechanism of adverse pregnancy,a study was carried out on 110 couples,57 of them with unexplained adverse pregnancy and 57 served as a control.A technique for the simultaneous staining of both nucleolar organizer regions and kinetochores of human chromosomes with silver was used.The results showed that the variations of chromosomal centromere kinetochore complex (CKC) in couples with adverse pregnancy were significantly high than of the control.The variations of CKC may be the main reason for the chromosomal nondisjunction during meiosis that is attributed to the adverse pregnancy.     

正常人染色体Cd结构的研究

本文采用Cd-NOR同步银染技术,对23例正常人染色体Cd结构变异、Cd结构消失、小Cd结构以及“Cd-NOR融合”作了分析。结果发现：(1)具有小Cd结构的染色体常涉及D, G组染色体;(2)Cd结构变异最常发生于1号和16号染色体上;(3)G组染色体上"Cd-NOR融合”频率显著高于其理论值;（4）正常人细胞中存在一定频率的Cd结构消失现象。本文还对人类近端着丝粒染色体易于不分离的原因作了初步讨论,并对此提出了新的解释。     

正常人染色体Cd结构的研究

本文采用Cd-NOR同步银染技术,对23例正常人染色体Cd结构变异、Cd结构消失、小Cd结构以及“Cd-NOR融合”作了分析。结果发现:(1)具有小Cd结构的染色体常涉及D、G组染色体;(2)Cd结构变异最常发生于1号和16号染色体上;(3)G组染色体上“Cd-NOR、融合”频率显著高于其理论值;(4)正常人细胞中存在一定频率的Cd结构消失现象。本文还对人类近端着丝粒染色体易于不分离的原因作了初步讨论,并对此提出了新的解释。     

正常人各年龄组染色体着丝粒点(Cd)研究

本文运用本室改良的Cd-NOR银染技术对80例4个年龄组的正常中国人的Cd变化进行了较系统的研究, 结果表明:(1)正常人随年龄增加,Cd消失的频率、Cd变异及Cd-NOR融合频率也相应增加,特别是Ⅲ、Ⅳ组(中、老年组)增加的频率尤为显著;(2)首次对Cd消失的过程提出了独特的观点,即Cd消失首先表现为Cd变小, 随着变小程度的加大,最终导致Cd消失;(3)在本研究中首次观察到单个Cd的现象,作者认为是细胞分裂中期染色体着丝一分为二的延迟现象。各年龄组间单Cd出现频率无统计学差异,同一年龄组中,2号染色体和1号染色体上单Cd出现频率显著高于理论值;(4)随年龄增高,Cd各项观察值的增高在男性与女性间未见明显的差异。 Abstract:The Cd variation of human chromosome in four groups of different age has been investigated.The result shows that the frequencies of Cd disappearing,size variation and Cd-NOR fusion increased with the age rising,especially in the group of aged people.We suggest that the variation of Cd shows the size changes first,and then disappears completely.We also observed some cells in which a few chromosomes shows only a single Cd in centromeric region.Cd variation in different age groups has no significant difference between the male and the female.     

BGC823和A549细胞染色体着丝粒点变异

癌细胞的一个显著细胞遗传学特征是染色体非整倍性畸变,但其畸变的机制至今仍然不清。因此,本文从与染色体分离直接相关的着丝粒点变异的角度,采用Cd-NOR同步银染技术对BGC823细胞和A549细胞染色体Cd变异进行了分析,以探索癌细胞非整倍性畸变的发生机制。结果表明：（1）BGC823细胞染色体Cd缺失率为1.75%、迟滞复制率为0.28%、小Cd率为1.82%、Cd-NOR融合率为0.95%,与正常人胚胎绒毛细胞染色体Cd相比较,BGC823细胞染色体Cd缺失和Cd-NOR融合显著升高（P＜0.0125）,而Cd迟滞复制和小Cd两者没有显著性差异。（2）A549细胞染色体Cd缺失率为2.73%、迟滞复制率为0.94%、小Cd率为1.73%、Cd-NOR融合率为0.71%,与正常人胚胎绒毛细胞染色体Cd相比较,A549细胞染色体Cd缺失和Cd迟滞复制显著升高（P＜0.0125）,而小Cd和Cd-NOR融合两者没有显著性差异。提示BGC823细胞染色体非整倍性畸变可能主要源于Cd缺失和Cd-NOR融合,而A549细胞染色体非整倍性畸变可能主要源于Cd缺失和Cd迟滞复制。     

染色体着丝点结构变化与习惯性流产的关系

为探讨染色体Cd结构变化与习惯性流产关系,采用Cd-NOR同步银染技术,对38例习惯性流产患者和42例正常人Cd结构变异、Cd结构消失、Cd结构最大横径和Cd-NOR融合进行测量和比较分析。发现习惯性流产患者的Cd结构变异和Cd结构消失的频率明显高于正常人,Cd结构最大横径明显小于正常人。Cd结构消失和Cd结构变异频率的增高以及Cd结构最大横径变小可能是影响习惯性流产的相关因素。 Abstract:To study the correlation between chromosome centromeric dots and habitual abortions,Cd variation,Cd loss,maximum diameter of Cd and Cd-NOR of 38 habitual abortion patients and 42 healthy persons were measured,compared and analysed with Cd-banding technique.It was found that the frequencies of Cd variation and Cd loss were obviously higher and maximum diameter of Cd was smaller in habitual abortion patients than those in healthy persons.The increase of frequencies of Cd variation and Cd loss and the decrease of maximum diameter of Cd might be the causes affecting habitual abortions.     

正常人胚胎绒毛细胞染色体着丝粒点(Cd)变异的研究

我们采用Cd-NOR同步银染技术,首次对正常人胚胎绒毛细胞染色体着丝粒点(Cd)变异作了研究,并将绒毛细胞染色体Cd变异与正常人外周血淋巴细胞体染色Cd变异进行了对比。在本研究中,我们观察到某些染色体存在Cd迟滞复制现象,并对此作了讨论。 Abstract:Centromeric dots(Cd)variation of chorion tissue chromosomes were studied by a simultaneous silver staining of both NOR and Cd.Comparison analysis of Cd variation for the chorionic villus samples and peripheral blood samples were carried out.We observe an event of Cd delaying reproduction and discuss the relation between the event and X chromosome delaying reproduction as well as chromosomeal nondisjunction.     

不良孕产史和自发性流产夫妇Dp、Gp 染色体研究

应用细胞遗传学的方法对巧例不良孕产史及自发性流产患者Dp⁺ 、Gp⁺ 染色体,和10例年龄相近的正常成年人染色体进行了研究,两组间随体联合（SAs),银染核仁形成区(Ag-NOR)助及银染随体联合（Ag-AA）的结果表明,各组间频率差异无显著性意义。     

不良孕产史和自发性流产夫妇Dp~ 、Gp~ 染色体研究

应用细胞遗传学的方法对15例不良孕产史及自发性流产患者Dp~ 、Gp~ 染色体,和10例年龄相近的正常成年人染色体进行了研究,两组间随体联合(SAS),银染核仁形成区(Ag-NOR)及银染随体联合(Ag-AA)的结果表明,各组间频率差异无显著性意义。     

着丝粒横裂和着丝粒并合及其在高等植物染色体进化中的意义

本文讨论了着丝粒横裂和并合及其在高等植物染色体进化中的意义。着丝粒横裂和着丝粒并合是两个矛盾又辩证统一的过程,是染色体的基本变异形式之一,它们同时影响着植物类群的染色体基数、核型对称性、连锁关系、交叉频率和位点等细胞遗传学的重要方面.从而在高等植物染色体进化中起着重要作用,着丝粒和端粒的复制模型为着丝粒的横裂与并合提供了可能的机理,但尚待直接的生物化学证据的证实,原始基数的确定是判别着丝粒横裂与并合的关键。     

Cytogenetic study of recurrent miscarriages and their parents

There is substantial evidence that genetic alterations are contributing factors to the risk for recurrent miscarriages. This study was conducted to determine the frequency and contribution of chromosomal abnormalities in miscarriages and in couples with recurrent miscarriages. We studied a total of 41 miscarriages and their parents with a history of 2–11 recurrent miscarriages. Chromosomal analysis from chorionic villus sampling (CVS) and fetal tissues were performed according to standard cytogenetic methods using G-banding technique. Major chromosomal aberrations and polymorphic variants were found in 51 and 4.8%, respectively. The chromosomal abnormalities were structural (34.4%) and numerical (65.1%) of which 26.1, 21.7, 8.7 and 8.7% were fetal sex aneuploid, triploid, mosaics and trisomic, respectively. Unbalanced and balanced rearrangements were found in 17.2 and 8.6% of all abnormalities, respectively. Major chromosomal abnormalities in couples were seen in 4.9%. The chromosomal abnormalities associated with pregnancy losses and recurrent miscarriages are mostly numerical ones. The incidence of balanced translocations found here is 4.9% which is near to the mode (about 3–6%) observed in the previous studies. Those frequencies are greater than in the general population (0.3%). This indicates that balanced translocations, seen in parents, have some importance in causing miscarriage. The major parental chromosomal aberrations are significantly associated with fetal wastage. Mosaicism should be taken into account for cytogenetic analyses of pregnancy losses. Thus, cytogenetic analyses should be recommended in couples with recurrent miscarriages, when clinical data fail to clarify the cause. The text was submitted by the authors in English.     

Cytogenetic study of recurrent miscarriages and their parents

There are substantial evidences that genetic alterations are contributing factors to the risk for recurrent miscarriages. This study was conducted to determine the frequency and contribution of chromosomal abnormalities in miscarriages and in couples with recurrent miscarriages. We studied a total of 41 miscarriages and their parents with a history of 2-11 recurrent miscarriages. Chromosomal analysis from chorionic villus sampling (CVS) and fetal tissues were performed according to standard cytogenetic methods using G-banding technique. Major chromosomal aberrations and polymorphic variants were found in 51 and 4.8%, respectively. The chromosomal abnormalities were structural (34.4%) and numerical (65.1%) of which 26.1, 21.7, 8.7 and 8.7% were fetal sex aneuploid, triploid, mosaics and trisomic, respectively. Unbalanced and balanced rearrangements were found in 17.2% and 8.6% of all abnormalities, respectively. Major chromosomal abnormalities in couples were seen in 4.9%. The chromosomal abnormalities associated with pregnancy losses and recurrent miscarriages are mostly numerical ones. The incidence of balanced translocations found here is 4.9% which is near to the mode (about 3-6%) observed in the previous studies. Those frequencies are greater than in the general population (0.3%). This indicates that balanced translocations, seen in parents, have some importance in causing miscarriage. The major parental chromosomal aberrations are significantly associated with fetal wastage. Mosaicism should be taken into account for cytogenetic analyses of pregnancy losses. Thus, cytogenetic analyses should be recommended in couples with recurrent miscarriages, when clinical data fail to clarify the cause.     

动物细胞系的染色体组型与遗传变异率分析

在建立国内首家犬,猫,猴,鼠传代细胞库,即7种动物肾细胞系（F－81,CRFK,MDCK,Vero,Vero-2,MA-104,BHK-21)的种子库和工作库的基础上,通过细胞染色体组型,G带核型,染色体数目变异率,结构畸变率分析,了解7种细胞系传代培养不同代次的染色体变异情况,以相应的细胞株皮下接种褐 形成肿瘤实验,软琼脂细胞克隆一苦恼经与植物凝集素作用下细胞凝集实验为对照,筛选出无致癌／致瘤性,符合细胞遗传学要求,无传染因子污染的细胞系（F－81,CRFK,Vero,Vero-2)或极低致癌性的MDCK细胞系用于制苗,发现肿瘤细胞系高变异率株可在裸鼠体内快速选育成功,细胞系染色体遗传特征决定致性质并具有种属特异性,得到一些100％成瘤和100％不成瘤的细胞株并了与染色体组型的关系,对于肿瘤的发病机理及实验治疗,都是非常好的模型,一些细胞系不仅成瘤而且还可转移（致恶性横纹肌样瘤的BHK－21和Vero 细胞株）,其他致瘤细胞株只成瘤不转移或不明显转移。     

罗伯逊易位分子机理初探

目的：探讨复发性自然流产与染色体罗伯逊易位间的关系。方法：采用人外周血淋巴细胞培养,常规G显带技术行染色体核型检查,并结合临床资料对其进行分析。结果：57对复发性自然流产夫妇中,检出罗伯逊易位染色体核型4例,检出率3.51%。结论：罗伯逊易位是导致复发性流产的重要原因之一,对复发性自然流产患者进行常规的染色体检查及遗传咨询具有一定的临床意义。     

Cytogenetic analysis in couples with recurrent miscarriages: a retrospective study from Punjab,north India

Human reproduction is considered as the most inefficient event as ～15–20% of human pregnancies end in miscarriage and in the product of miscarriages, chromosomal anomalies are a common occurrence. The aim of the present retrospective study was to assess the frequency of chromosomal aberrations in couples with recurrent miscarriages in the region of Punjab and to compare with worldwide frequencies. In this study, a total of 440 cases were referred between the period 1995–2015. After lymphocyte culturing, giemsa–trypsin banding was done for each case to assess the chromosomal anomalies. The frequency of chromosomal aberrations among couples was found to be 3.41% in our study. Among these aberrations, balanced reciprocal translocations formed the largest group with 60% anomalies. We would conclude that clinicians should understand the importance of chromosomal analysis in these couples and refer them for karyotyping after two miscarriages to rule out the possible genetic cause of recurrent miscarriages.     

Chromosomal abnormalities as a cause of recurrent abortions in Egypt

BACKGROUND:

In 4%-8% of couples with recurrent abortion, at least one of the partners has chromosomal abnormality. Most spontaneous miscarriages which happen in the first and second trimesters are caused by chromosomal abnormalities. These chromosomal abnormalities may be either numerical or structural.

MATERIAL AND METHODS:

Cytogenetic study was done for 73 Egyptian couples who presented with recurrent abortion at Genetic Unit of Children Hospital, Mansoura University.

RESULTS:

We found that the frequency of chromosomal abnormalities was not significantly different from that reported worldwide. Chromosomal abnormalities were detected in 9 (6.1%) of 73 couples. Seven of chromosomal abnormalities were structural and two of them were numerical.

CONCLUSION:

Our results showed that 6.1% of the couples with recurrent abortion had chromosomal abnormalities, with no other abnormalities. We suggest that it is necessary to perform cytogenetic in vestigation for couples who have recurrent abortion.     

Current status of preimplantation genetic diagnosis in Japan

This is a retrospective study aimingto clarify the current status of preimplantation genetic diagnosis (PGD) in Japan. Our data were collected from 12 facilities between September 2004 and September 2012, and entered into a database. A majority of PGD in Japan was performed for balanced structural chromosomal abnormalities in couples with recurrent miscarriage. PGD for monogenic diseases was performed only in two facilities. The average maternal age was 38 years for monogenic diseases and 40 years for chromosomal abnormalities. Overall there have been671 cycles to oocyte retrieval reported. Of these cycles, 85% (572 cycles)were for chromosomal abnormalities, and 15% (99 cycles) for monogenic diseases. Diagnosis rates in the current study were 70.8% for monogenic diseases and 94.0% for chromosomal abnormalities. Rates of embryo transfer of PGD were 62.7% for monogenic diseases and 25.5% for chromosomal abnormalities. Clinical pregnancy rates per embryo transfer were 12.0% for monogenic diseases and 35.6% for chromosomal abnormalities. Our study is the first PGD report from all facilities which had the approval of the ethics committee of the Japanese Society of Obstetrics and Gynecology. We have built a basis for gathering continuous PGD data in Japan.     

Somatic chromosomal abnormalities in infertile men and women

Infertility--the inability to achieve conception or sustain a pregnancy through to live birth--is very common and affects about 15% of couples. While chromosomal or genetic abnormalities associated with azoospermia, severe oligozoospermia or primary ovarian failure were of no importance for reproduction prior to the era of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), advances in assisted reproductive techniques (ART) now enable many infertile couples to have children. These developments have raised the question of the genetic consequences of ICSI: concerns of the potential harm of the invasive procedure and concerns about the genetic risk. The infertile male and female definitely have an increased risk to carry a chromosomal abnormality. Detection of such an abnormality is of fundamental importance for the diagnosis of infertility, the following treatment, the evaluation of the risk for the future child and the appropriate management of the pregnancy to be obtained. Therefore, cytogenetic screening of both partners is mandatory prior to any type of ART. The present review is based on several surveys on male and female infertility and analyzes the types and frequencies of the different reported chromosome abnormalities according to the type of impairment of spermatogenesis and the type of treatment planned or performed. With regard to assisted reproductive techniques (especially ICSI) the main types of chromosomal abnormalities are discussed and their potential risks for ICSI. If available, reported cases of performed ICSI and its outcome are presented. The detection of an abnormal karyotype should lead to comprehensive genetic counselling, which should include all well-known information about the individual type of anomaly, its clinical relevance, its possible inheritance, the genetic risk of unbalanced offspring, and the possibilities of prenatal diagnosis. Only this proceeding allows at-risk couples to make an informed decision regarding whether or not to proceed with ART. These decisions can be made only when both partners have clearly understood the genetic risks and possible consequences when ART is used.     

Vascular function in alcohol-treated pregnant and nonpregnant mice

The effect of alcohol on maternal vascular adaptations to pregnancy is unknown. This study was designed to determine the effect of alcohol consumption on nitric oxide-mediated vascular function in mice during pregnancy. Female pregnant or nonpregnant C57BL/6J mice were fed a control diet or a liquid diet of 25% ethanol-derived calories for 13 days (from gestational days 6-18). Phenylephrine vasoconstriction was blunted in pregnancy compared with the nonpregnant state due to enhanced nitric oxide modulation, which was impaired by ethanol exposure. Although the EC50 and maximal responses to methacholine were not different in nonpregnant vs. pregnant mice, the nitric oxide component to methacholine-induced vasorelaxation was greater in the pregnant mice. Interestingly, alcohol affected only the pregnant animals in their response to methacholine. These data indicate that alcohol reduced the nitric oxide modulation of vascular response, which was more pronounced during pregnancy. These studies provide novel information regarding the effects of alcohol on the maternal vascular system during pregnancy and thereby contribute to further understanding of the adverse effects associated with prenatal alcohol exposure.     

Chromosome studies in 2136 couples with spontaneous abortions

Summary Two thousand one hundred and thirty six couples with one or more spontaneous abortions (SAB) before 13 weeks of gestation and with or without one normal liveborn child (NLC) were karyotyped. In 4.31% of the couples one partner was a carrier of a major chromosomal abnormality. Couples with SAB only have 2-fold more chromosomal aberrations than couples with SAB and NLC. A correlation between the frequency of chromosomal abnormalities and the number of SAB was observed. Finally, the various types of chromosome aberrations were analysed.