精子的表观遗传学研究进展

表观遗传学是研究DNA序列未发生变化但表型却发生可遗传改变的一门学科,其研究内容包括DNA甲基化、组蛋白修饰、非编码RNA调控等几个方面,任何一方面异常都可能影响染色质的结构和基因表达。在精子发生及受精过程中表观遗传信息都发生了较大变化,因此了解精子的表观遗传学变化对研究后代遗传信息的改变至关重要。本文对精子的表观遗传学信息进行综述,并对辅助生殖技术所带来的遗传风险作简要探讨。     

精子的表观遗传学研究进展

表观遗传学是研究DNA序列未发生变化但表型却发生可遗传改变的一门学科，其研究内容包括DNA甲基化、组蛋白修饰、非编码RNA调控等几个方面，任何一方面异常都可能影响染色质的结构和基因表达。在精子发生及受精过程中表观遗传信息都发生了较大变化，因此了解精子的表观遗传学变化对研究后代遗传信息的改变至关重要。本文对精子的表观遗传学信息进行综述，并对辅助生殖技术所带来的遗传风险作简要探讨。     

实施辅助生殖技术女性患者自我接纳与主观幸福感的关系研究

目的探讨实施辅助生殖技术女性患者自我接纳与主观幸福感的关系。方法采用自我接纳问卷和纽芬兰大学幸福度量表,对268例实施辅助生殖技术的女性患者进行问卷调查。结果实施辅助生殖技术的女性患者的自我接纳及主观幸福感均处于中等偏低水平,自我接纳总分及其各维度与主观幸福感总分、正性情感及正性体验呈显著正相关,与负性情感及负性体验呈显著负相关。自我接纳及自我评价是实施辅助生殖技术的女性患者主观幸福感的正向预测因子。结论自我接纳是实施辅助生殖技术的女性患者主观幸福感的重要影响因素。     

辅助生殖技术子代的心血管功能安全性研究进展

随着辅助生殖技术(ART)的广泛应用,动物和人体心血管安全性的研究表明,ART对其子代的心血管功能有潜在的不良影响。本文从血管动脉粥样硬化、血压、心血管重建及心功能、胰岛素抵抗等方面讲述ART对子代的心血管功能的影响,并就ART妊娠并发症、ART技术本身、父母不孕因素及表观遗传四方面阐述其可能的机制。     

双酚A对男性生殖毒性的研究进展

环境干扰物对男性生殖的毒性作用是研究热点。双酚A(BPA)是一类环境雌激素,与男性生殖健康以及其他疾病如糖尿病、肥胖、心血管疾病及癌症等相关。BPA可通过拟雌激素或抗雄激素作用干扰人体内分泌系统,如干扰下丘脑-垂体-睾丸轴、调节激素合成相关基因的表达和酶活性、影响激素及其受体功能等,也可通过修饰DNA甲基化、表观遗传效应等方式,引起生精障碍、少弱畸精子症等导致男性不育。本文综述BPA暴露对男性精子发生、精液质量及生殖内分泌系统的毒性作用。     

蛋白质精氨酸甲基化转移酶与哺乳动物生殖

蛋白质精氨酸甲基化修饰是由蛋白质精氨酸甲基转移酶(Protein arginine methyltransferases,PRMTs)催化完成,它是表观遗传水平重要的修饰方式之一。组蛋白H3、H4上的精氨酸甲基化修饰在配子发生、受精卵的形成、胚胎着床以及胚胎发育中广泛存在。精氨酸甲基化活动的异常会导致血清性激素水平紊乱,影响子宫内膜的动态重塑。此外,精氨酸甲基化酶蛋白在子宫内膜各个时期的表达具有差异,可能在子宫内膜容受性建立过程中有重要作用。目前,精氨酸甲基化活动在哺乳动物生殖过程中的作用尚未明确,进一步阐明其分子机制显得尤为重要。     

生殖医学杂志2015年征订工作正式启动

<正>主管单位:国家卫生和计划生育委员会主办单位:北京协和医院国家人口计生委科学技术研究所社长:马旭主编:郎景和办刊宗旨:为男女性生殖生理、辅助生殖技术、生育调节、生殖疾病、遗传等方面的基础研究和临床诊治     

精子DNA损伤与辅助生殖技术

随着辅助生殖技术的广泛开展,精子评估已由传统的精液常规分析向细胞、分子水平深入发展。精子DNA损伤是反映男性生育力的一个新指标。精子DNA损伤的发生机制包括精子染色质包装与分离异常、氧化应激、细胞凋亡异常等。精子染色质结构分析是目前检测精子DNA损伤最常用的方法之一。精子DNA损伤可能与辅助生殖技术治疗结局、复发性自然流产、增加ICSI后代遗传风险相关。采取口服抗氧化药物、取睾丸精子行ICSI、预冻存精子、去除病因以及中医中药等治疗对策可能会降低精子DNA损伤程度,进而提高辅助生殖技术成功率。本文主要就精子DNA损伤的机制与检测方法、DNA损伤与生殖结局以及辅助生殖技术中与DNA损伤相关的治疗对策作一综述。     

人类辅助生殖技术管理办法

第一章　总则第一条　为保证人类辅助生殖技术安全、有效和健康发展 ,规范人类辅助生殖技术的应用和管理 ,保障人民健康 ,制定本办法。第二条　本办法适用于开展人类辅助生殖技术的各类医疗机构。第三条　人类辅助生殖技术的应用应当在医疗机构中进行 ,以医疗为目的 ,并符合国家计划生育政策、伦理原则和有关法律规定。禁止以任何形式买卖配子、合子、胚胎。医疗机构和医务人员不得实施任何形式的代孕技术。第四条　卫生部主管全国人类辅助生殖技术应用的监督管理工作。县级以上地方人民政府卫生行政部门负责本行政区域内人类辅助生殖技术的…     

生殖医学杂志2015年征订工作正式启动

<正>主管单位:国家卫生和计划生育委员会主办单位:北京协和医院国家人口计生委科学技术研究所社长:马旭主编:郎景和办刊宗旨:为男女性生殖生理、辅助生殖技术、生育调节、生殖疾病、遗传等方面的基础研究和临床诊治提供学术论坛,介绍生殖医领域的研究成果,推广新技术和新方法。栏目设置:专家论坛临床研究综述实验研究短篇论著技术与方法病例报告基层生殖健康等     

ART success and in vivo sperm cell selection depend on the ultramorphological status of spermatozoa

Management of male infertility has recently shifted from treatment of the subfertile man towards techniques of assisted reproduction (ART). This study aimed to evaluate the possible role of the ultramorphological status of the spermatozoon with respect to sperm selection in vivo and prediction of ART success. Ultramorphological sperm parameters were assessed retrospectively for 92 males with sufficient sperm density (10⁷ spermatozoa ejaculate⁻¹) whose wives conceived following a stepwise discarding of the female genital tract barriers, using intra-uterine insemination (IUI) ( n =26), in vitro fertilization (IVF) ( n =45) or intracytoplasmic sperm injection (ICSI) ( n =21). In parallel, sperm samples of 71 fertile males were examined. Normal ultramorphology of all head and tail subcellular organelles was found to be essential for the ability of spermatozoa to pass the lower female genital tract. The ultramorphological migration threshold for this barrier is apparently higher than that essential for oocyte fertilization. No specific indication associated with passage through the upper genital tract was found. A high prevalence of axonema defects was found to impair the ability of sperm cells to penetrate the oocyte investment. The natural fertility index, based on routine sperm parameters and the ultrastructural status of the spermatozoon's subcellular organelles was confirmed to be beneficial for directing patients to ART. A discriminative score based on axonema integrity was found to contribute additional information for the first choice decision between conventional ART and ICSI (75% prediction ability). Thus it may be helpful in finding the simplest and least expensive procedure with the greatest long-term chance for pregnancy.     

Sperm preparation: state-of-the-art--physiological aspects and application of advanced sperm preparation methods

For assisted reproduction technologies (ART), numerous techniques were developed to isolate spermatozoa capable of fertilizing oocytes. While early methodologies only focused on isolating viable, motile spermatozoa, with progress of ART, particularly intracytoplasmic sperm injection (ICSI), it became clear that these parameters are insufficient for the identification of the most suitable spermatozoon for fertilization. Conventional sperm preparation techniques, namely, swim-up, density gradient centrifugation and glass wool filtration, are not efficient enough to produce sperm populations free of DNA damage, because these techniques are not physiological and not modeled on the stringent sperm selection processes taking place in the female genital tract. These processes only allow one male germ cell out of tens of millions to fuse with the oocyte. Sites of sperm selection in the female genital tract are the cervix, uterus, uterotubal junction, oviduct, cumulus oophorus and the zona pellucida. Newer strategies of sperm preparation are founded on: (i) morphological assessment by means of 'motile sperm organelle morphological examination (MSOME)'; (ii) electrical charge; and (iii) molecular binding characteristics of the sperm cell. Whereas separation methods based on electrical charge take advantage of the sperm's adherence to a test tube surface or separate in an electrophoresis, molecular binding techniques use Annexin V or hyaluronic acid (HA) as substrates. Techniques in this category are magnet-activated cell sorting, Annexin V-activated glass wool filtration, flow cytometry and picked spermatozoa for ICSI (PICSI) from HA-coated dishes and HA-containing media. Future developments may include Raman microspectrometry, confocal light absorption and scattering spectroscopic microscopy and polarization microscopy.     

Male age is not an independent factor to affect the outcome of assisted reproductive techniques

Controversy exists whether advanced male age is associated with poor sperm quality and subsequent failure in the assisted reproductive techniques (ART). The purpose of this study was to evaluate the effect of male age on sperm quality and the outcome of ART as well as the association of male age with other relevant factors, particularly with the female age. A retrospective study was performed in order to evaluate the effect of male age on the sperm parameters in 880 routine seminal analyses. Additionally, sperm parameters were also compared among different age groups in 919 cases with male factor infertility who had been included in an ART programme. The laboratory and clinical results of ART (fertilization rate, number and quality of embryos transferred, as well as pregnancy rates) were compared according to different age groups. The results were also evaluated by one-way correlation and also step-wise logistic regression analysis to identify the interactions and correlations between different parameters. There were no statistically significant differences between male age groups in terms of sperm concentration, motility and morphology either in routine seminal analyses or in ART groups. In the ART group, a statistically significant linear correlation was present between male and female ages. Male age was increasing in parallel to female age. Female age was also correlated significantly with ART results. In one-way correlation analysis, male age was found to be correlated with the pregnancy rate, but not with fertilization rate and the quality of the transferred embryos. However, regression analysis revealed that correlation between male age and pregnancy results was simply dependent on the effect of the female age. Seminal parameters did not reveal a significant change with the increasing male age. The effect of male age on ART results in cases with male factor infertility is not a direct effect but a reflection of the negative impact of the parallel increase in the female age.     

子宫内膜异位症伴不育治疗进展

子宫内膜异位症(EMT)导致不育的治疗方法主要有药物、手术、手术药物联合、辅助生殖技术(ART)等。近年提倡先行腹腔镜手术以解除解剖方面的因素,ART也逐渐成为EMT伴不育患者的一线治疗方案。另外免疫调节剂和细胞因子调节剂的动物实验结果也提供了非激素药物治疗的新方向。     

Microsurgical varicocelectomy for infertile couples with advanced female age: natural history in the era of ART

Varicocele represents the most common cause of male infertility, and most reports indicate that varicocelectomy has a beneficial effect on male fertility and pregnancy outcome. Assisted reproductive technologies (ARTs) are an alternative to varicocelectomy for the management of couples with a varicocele. The age of the female partner is important in the decision-making process; however, the true influence of female age on pregnancy outcome following varicocelectomy or ART in these couples is unknown. We evaluated the outcomes of 2 cohorts of infertile men with a varicocele and a female partner 35 years of age or older; one group selected varicocelectomy and the other a nonsurgical approach. We reviewed a group of consecutive infertile men who underwent microsurgical varicocelectomy and whose partners are 35 years of age or older (n = 110). We also reviewed a consecutive group of men with varicoceles who elected not to have surgery and whose partners are 35 years of age or older (n = 94). The outcome measures included changes in semen parameters, pregnancy rates (assisted and unassisted), and use of ART. The surgical and nonsurgical groups had comparable semen parameters and female ages. Mean sperm concentration and motility increased significantly after varicocelectomy (P < .05). At a mean of 30 months follow-up, 35% of couples in the surgical group achieved a spontaneous pregnancy and an additional 6% achieved a pregnancy via ART (20% of this group attempted ART). In the nonsurgical group, 25% achieved a spontaneous pregnancy and an additional 16% achieved a pregnancy with ART (40% of this group attempted ART). This study on the natural history of infertile men with varicocele and advanced female age suggests that the surgical and nonsurgical approaches offer comparable pregnancy outcome (combined assisted and unassisted pregnancy rates are about 40%). Overall, these data suggest that varicocelectomy is an acceptable option for couples with advanced female age, but other female factors must be considered in the decision-making process.     

Declining trends in conception rates in recent birth cohorts of native Danish women: a possible role of deteriorating male reproductive health

Recent findings of poor semen quality among at least 20% of normal young men in Denmark prompted us to use unique Danish registers on births and induced abortions to evaluate a possible effect of the poor male fecundity on pregnancy rates among their presumed partners--the younger cohorts of women. We have analysed data from the Danish birth and abortion registries as well as the Danish registry for assisted reproduction (ART) and defined a total natural conception rate (TNCR), which is equal to fertility rate plus induced abortion rate minus ART conception rate. A unique personal identification number allowed the linkage of these databases. Our database included 706,270 native Danish women born between 1960 and 1980. We used projections to estimate the fertility of the later cohorts of women who had not yet finished their reproduction. We found that younger cohorts had progressively lower TNCR and that in terms of their total fertility rate, the declining TNCR is compensated by an increasing use of ART. Our hypothesis of an ongoing birth cohort-related decline in fecundity was also supported by our finding of increasing and substantial use of ART in the management of infertility of relatively young couples in the later cohorts. Furthermore, the lower rates of induced abortion among the younger birth cohorts, often viewed as a success of health education programs, may not be fully explained by improved use of contraception. It seems more likely that decreased fecundity because of widespread poor semen quality among younger cohorts of otherwise normal men may explain some of the observed decline in conception rates. This may imply increasing reproductive health problems and lower fertility in the future, which is difficult to reverse in the short term. The current and projected widespread use of ART in Denmark may be a sign of such an emerging public health problem.     

卵子质量评估的意义和手段

对卵子发育潜能进行评估能够改善人类辅助生殖的总体结局,因此是辅助生殖技术的重要环节。本文的目的是总结卵子形态学特征的重要意义,并介绍部分非形态学评估方法。主要讨论的形态学结构包括卵冠丘复合物、纺锤体、透明带、空泡、折光小体、极体、卵子形状、胞浆颗粒化、卵周隙等特征。这些文献得出的不同结论说明,对人类卵子的形态学观察和评估指标的预测价值,需要进一步的研究与合作来证实。     

Posthumous reproduction: current and future status

Posthumous reproduction became possible with the technologies of sperm cryopreservation and ART. The legal and social status of children born as a result of these technologies continue to evolve. The proper disposition of unwanted stored gametes and embryos remains unknown. Physicians are increasingly asked to make quick judgments on posthumous gamete retrieval. The procedures for gamete harvest are technically simple; however, one must carefully select cases with definitive prior intent to have children. There is a need for standardized legal protocols to protect the physician and the patient. The physician must use sound judgment and comply with accepted standards, when present, before performing any service for posthumous sperm retrieval and reproduction.     

Mechanisms and clinical correlates of sperm DNA damage

Among the different DNA anomalies that can be present in the male gamete, DNA fragmentation is the most frequent, particularly in infertile subjects. There is now consistent evidence that a sperm containing fragmented DNA can be alive, motile, morphologically normal and able to fertilize an oocyte. There is also evidence that the oocyte is able to repair DNA damage; however, the extent of this repair depends on the type of DNA damage present in the sperm, as well as on the quality of the oocyte. Thus, it is important to understand the possible consequences of sperm DNA fragmentation (SDF) for embryo development, implantation, pregnancy outcome and the health of progeny conceived, both naturally and by assisted reproductive technology (ART). At present, data on the consequences of SDF for reproduction are scarce and, in many ways, inconsistent. The differences in study conclusions might result from the different methods used to detect SDF, the study design and the inclusion criteria. Consequently, it is difficult to decide whether SDF testing should be carried out in fertility assessment and ART. It is clear that there is an urgent need for the standardisation of the methods and for additional clinical studies on the impact of SDF on ART outcomes.     

辅助生殖技术出生的学龄期儿童行为发育的随访研究

目的探讨通过辅助生殖出生的学龄期儿童行为发育(社会能力及行为能力)是否与自然受孕出生儿童存在差异。方法选择我院2001年3月至2009年3月通过辅助生殖技术出生的6~11岁学龄期儿童125例(ART组),并随机抽取同年龄段自然受孕出生儿童203例作为对照(NC组),采用Achenbach儿童行为量表(CBCL量表)评估儿童社会能力及行为能力。结果男童组,辅助生殖出生儿童(ART组)与自然受孕出生儿童(NC组)在社会能力各项评分及行为能力评分异常者比例方面均无统计学差异(P0.05);女童组,ART组与NC组相比,其活动能力评分较低(4.74±2.16vs.5.52±2.20,P0.05),但两组行为能力各项评分异常者比例无统计学差异(P0.05)。对影响女孩活动能力因素进行多重线性回归分析发现,儿童年龄及母亲教育程度对活动能力的影响有统计学意义(P0.05),而是否为试管婴儿、是否为双胎、身高、体重等因素对女孩的活动能力的影响无统计学意义(P0.05)。结论辅助生殖出生的学龄期女童的活动能力评分低于自然受孕出生的女童,男童及女童的其他行为发育指标与同年龄段自然受孕出生儿童无显著差异。