精子DNA损伤的研究进展

随着男性不育症发病率的升高,精液常规检测已不足以精确评估男性生育力。近年来,精子DNA损伤检测作为一项评估精子质量及男性生育力更精准的指标,逐步成为生殖医学领域的研究热点。精子DNA损伤的机制包括精子发生异常、氧化应激损伤、精子凋亡异常等。目前,精子染色质结构分析法(SCSA)已经成为检测精子DNA完整性的金标准。精子DNA损伤可能与男性不育、辅助生殖结局及后代生长、发育相关。笔者拟就精子DNA损伤的机制、检测方法、对男性生育力的影响及其与辅助生殖技术的关系进行综述,旨在为男性不育症的临床诊断提供依据。     

Present-day management of male infertility

An overview is presented of the management of impaired fertility in men. Laboratory examination of semen, the primary determination of fertility status, is complicated by the lack of criteria of "normal" parameters. Most seminologists agree that fertility is compatible with a count below 20 million/ml, but the quality of motility and morphology is the critical factor. Consecutive semen analyses in the same person can also show great variation, so several specimens should be studied over a period of months. A definite cause for infertility can be found in less than 10% of cases. Half of those with a known cause are azoospermic due to an obstructive lesion of the conducting pathways or to total failure of spermatogenesis. Varicocele and immunolgoic aspects of infertility have attracted recent interest. New investigational methods have identified a substantial retrograde flow down the internal spermatic vein whenever a true varicocele is palpable. Suprainguinal ligation of the internal spermatic vein has been performed in these cases and estimates of improvement in the semen profile range from 30-80% of cases. However, many clinicians have reservations about the overall role of spermatic venous reflex in male infertility. When a significant titer of antibodies is noted, corticosteroids are generally administered. Despite little evident benefit, the trend toward prolonged treatment of infertility with pituitary hormones and stimulants continues. Increasingly, the infertile couple is being treated as a unit. Since specific measures seldom improve the semen profile, attention should be focused on improvement of opportunity for any effective sperm to achieve fertilization. There has been renewed interest in the cervical insemination cap method. About 14% of couples where the man shows seminal impairment conceived by this method, provided some of the sperm are of normal morphology. Artificial insemination with pooled stored sperm has produced disappointing results.     

线粒体功能与精子活力

精子活力是衡量精液质量和男性生育力的一个重要指标,在男性不育患者中约19％为精子活力低下所致。精子运动所需能量来自线粒体呼吸链的氧化磷酸化,各种原因导致的线粒体结构和功能改变,如膜电位的降低,酶活性或表达量异常以及线粒体DNA（mtDNA）的突变或缺失等均可导致线粒体能量合成障碍,精子活力降低。对近年有关线粒体功能与精子活力相关性研究进展综述,旨在探讨精子活力低下的发病机制以及临床治疗弱精子症的可能途径。     

Adolescent beliefs about infertility

PURPOSE: Explore adolescents' definition of fertility and range of beliefs regarding causes of infertility. METHODS: Qualitative study involving five focus groups that met between April 2001 and December 2001 at a hospital-based adolescent health center. All groups were led by one experienced moderator and observed by two investigators. Audiotapes of the group discussions were transcribed and reviewed independently by three investigators who met and reached consensus on underlying themes. RESULTS: Most adolescents generally understood fertility as the ability to become pregnant. Ten themes emerged as causes of infertility. Anatomic/gynecologic causes generated the most responses and most detailed discussion (e.g., "The coating on the egg is too hard and the sperm can't get in to fertilize the egg."). Other commonly mentioned causes were male factors (e.g., "He cannot produce sperm."), sexually transmitted infections (e.g., "like chlamydia caused scarring in the fallopian tubes"), genetics (e.g.,"a birth defect") and substance use (e.g., "if a man smoke weed all day, the egg may not develop because of problems with his sperm"). Less commonly mentioned themes were stress, contraception, environmental toxins, violence and injury. CONCLUSIONS: Most adolescents defined fertility as the ability to become pregnant and reported an extensive range of beliefs about the causes of infertility. Providers should consider eliciting adolescents' definitions of fertility and also exploring beliefs about causes of infertility with their patients when counseling about sexuality and contraception to determine if an adolescent has inaccurate beliefs about their fertility.     

IMPROVEMENT OF SEXUAL ACTIVITY,PREGNANCY RATE,AND LOW PLASMA TESTOSTERONE AFTER BILATERAL VARICOCELECTOMY IN IMPOTENCE AND MALE INFERTILITY PATIENTS

To evaluate the effects of bilateral varicocelectomy on sexual activity, testicular volumes, semen quality, and serum hormone levels in impotence and male infertility patients, 48 patients were studied from an outpatient clinic from May 1998 to March 2001. The mean age was 37 &#45 5.9; 16 patients were complaining of erectile dysfunction and 32 patients were complaining of male infertility. The mean duration of impotence was 3.3 &#45 2.4 years and for male infertility was 3.8 &#45 3.2 years. Sexual and reproductive history was taken for erectile dysfunction and male infertility patients. General, local examination, and laboratory investigations were done for all patients. Preoperative and postoperative testicular volumes; semen parameters, including semen volume, sperm count, and motility; and morphology and hormonal parameters, including LH and FSH, and testosterone levels were measured. All patients were followed up for 3-36 months after varicocele repair. Left and right testicular volume was improved in impotence and male infertility patients and fertility groups, but this improvement was not statistically significant ( p >.25). The semen volume was significantly increased in male infertility patients and fertility group ( p <.05), but there was no statistical significant difference in impotent patients ( p >.25). The sperm count was improved in male infertility patients and fertility group, but this improvement was not statistically significant ( p >.25), and in impotent patients there was no significant difference ( p >.40). The sperm motility was very significantly increased in male infertility patients and the fertility group ( p <.0005), and highly significantly increased in impotent patients ( p <.005). The abnormal forms were not statistically significant in impotence and male infertility patients ( p >.40), but significantly decreased in the fertility group ( p <.05). Serum testosterone was very significantly increased in impotence and male infertility patients ( p <.0005) and was highly significantly increased in fertility groups ( p <.005). Serum FSH was improved in impotence and male infertility patients, but this improvement was not statistically significant ( p >.10), and in fertility groups of male infertility patients, the results showed a statistically significant increase ( p <.05). Serum LH was not statistically significant in impotence and male infertility patients ( p >.10), and was significantly increased in fertility groups ( p <.05). The improvement of sexual activity was 50-75%, the pregnancy rate for their partners was 37% and increased plasma testosterone levels over a period of 3 years of follow-up after varicocele repair.     

影响精液质量的因素

精液异常是男性不育的主要指征,拥有健康精液是优生优育的重要保证,随着科学技术的发展,各种影响生育的不良因素被逐渐认识。据报道,近几年我国育龄男性精液质量异常人数呈上升趋势,有关人员曾对此做过研究和统计,其中包括对一次性射精量、精液黏稠度、精液液化时间、以及精子总数、精子密度、正常精子形态、精子运动情况和精子成活率、活动率等,通过流行病学调查分析认为,造成精液异常的主要原因除年龄因素之外,物理因素、化学因素、生物因素、营养因素、病理因素以及不良的生活习惯都有可能对其产生影响。参照WHO标准,结合我国相关调查,总结造成育龄男性精液异常的各种原因,对确保精液质量的健康大有意义。因此,加强对环境的保护,调整生活方式,保持良好的身体状态十分重要。     

线粒体功能与精子活力

精子活力是衡量精液质量和男性生育力的一个重要指标,在男性不育患者中约19%为精子活力低下所致。精子运动所需能量来自线粒体呼吸链的氧化磷酸化,各种原因导致的线粒体结构和功能改变,如膜电位的降低,酶活性或表达量异常以及线粒体DNA（mtDNA）的突变或缺失等均可导致线粒体能量合成障碍,精子活力降低。对近年有关线粒体功能与精子活力相关性研究进展综述,旨在探讨精子活力低下的发病机制以及临床治疗弱精子症的可能途径。     

先天性肾上腺皮质增生伴男性不育诊治一例及相关文献复习

先天性肾上腺皮质增生症（congenital adrenal hyperplasia，CAH）患者肾上腺皮质类固醇激素合成障碍，是一种常染色体隐性遗传病，最常见为21-羟化酶缺陷型，可影响男性生育力。男性CAH患者不育主要是由于肾上腺残余瘤和促性腺激素水平的改变。CAH罕见发病，症状常不典型，临床容易漏诊，早期发现并治疗可改善男性患儿成年后的生殖功能。CAH主要使用糖皮质激素治疗，部分成年患者可恢复生育能力；不能恢复自然生育能力的可通过辅助生殖技术生育；明确诊断后尽早进行精子冷冻保存。报道我院2018年诊治的1例CAH男性不育患者的辅助生殖助孕治疗过程，对其临床资料进行整理和分析，通过文献复习该疾病的发病机制和对男性生育力的影响。     

解脲支原体感染与精液质量关系临床研究

目的 探讨解脲支原体感染对精液质量的影响.方法 选2010年3月～2011年12月在某院就诊的不育男性患者163例,同时收集147例正常生育男性作为对照组,比较两组人群解腺支原体感染情况,同时比较不育组阳性者与对照组阴性者精液参数.结果 解脲支原体感染与患者不育存在显著的相关(P＜0.01);不育组UU阳性者与生育组UU阴性者精液量、pH值,差异无统计学意义(P＞0.05);不育组UU阳性者精子密度、精子活动率、a+b均显著低于生育组UU阴性者,差异均有统计学意义(P＜0.05);而精子畸形率显著高于生育组UU阴性者,差异有统计学意义(P＜0.05).结论 解脲支原体感染可严重影患者的精液质量,造成男性患者的不育.     

Cyanidin-3-O-Glucoside Supplement Improves Sperm Quality and Spermatogenesis in a Mice Model of Ulcerative Colitis

Impaired fertility and low sperm quality are the global health problem with high attention. It has been noted that inflammation may impact fertility by affecting testicular spermatogenesis. Cyanidin-3-O-glucoside is a natural functional pigment with various health benefits. Nevertheless, studies on the mechanism by which C3G protects male reproduction in mice with ulcerative colitis remain scarce. The purpose of this study is to illustrate the potential mechanism of C3G for improving impaired fertility caused by colitis. A DSS-induced colitis model was applied to assess the effects of sperm quality with colitis and the health benefit role of C3G. Results indicated that C3G-treated mice exhibited higher body weight, longer colon length, less crypt damage and focal inflammation infiltration. Being consistent with that, low sperm count, low testis weight, high inflammation levels and abnormal thickness of seminiferous epithelium also observed in the DSS group were significantly recovered upon C3G treatment. These findings suggested that colitis has a close link to impaired fertility. Further analysis found that C3G could significantly suppress the inflammatory mediators in serum. Results conjointly indicated that C3G might improve the impaired fertility of mice with colitis by inhibiting inflammatory cytokines through the blood–testis barrier. C3G could be a promising daily supplement for ameliorating impaired fertility caused by colitis.     

Semen quality and fertility of men employed in a South African lead acid battery plant

Previous studies of the associations of measures of occupational lead exposure with measures of semen quality and infertility among male workers have produced conflicting results. The current study was undertaken to examine these associations among a population of workers with a broad range of measures of current and historical lead exposure. Ninety-seven lead-exposed workers from a South African lead acid battery facility provided semen samples that were analyzed for sperm density, sperm count, sperm motility, sperm morphology, and presence of antisperm antibodies. Questionnaire data were collected for reported histories of sub- or infertility. Current blood leads ranged from 28 to 93 μg/dl. Semen lead ranged from 1 to 87 μg/dl. Reasonably consistent and significant associations were found between an increased percentage of sperm with abnormal morphology and higher measures of current blood lead, cumulative blood lead, and duration of exposure. An increased percent of immotile sperm was associated only with zinc protoporphyrin (ZPP) among the lead exposure measures. There were no associations of sperm density or sperm count with any of the lead exposure measures. A weak association of increased percent of sperm with antisperm antibodies with increased semen lead was present. There were no consistent associations of measures of lead exposure with measures of fertility or procreativity. This study, while supporting the association of lead exposure with increased risk of abnormal sperm morphology seen in some previous studies, does not lend support to previously reported associations of sperm density or count or infertility with measures of lead exposure. However, the relatively high range of current blood leads, high prevalence of abnormalities in semen quality, and the lack of a control population, suggest that these negative findings should be interpreted with caution. Am. J. Ind. Med. 32:369–376, 1997. © 1997 Wiley-Liss, Inc.     

Creatine Metabolism in Female Reproduction,Pregnancy and Newborn Health

Creatine metabolism is an important component of cellular energy homeostasis. Via the creatine kinase circuit, creatine derived from our diet or synthesized endogenously provides spatial and temporal maintenance of intracellular adenosine triphosphate (ATP) production; this is particularly important for cells with high or fluctuating energy demands. The use of this circuit by tissues within the female reproductive system, as well as the placenta and the developing fetus during pregnancy is apparent throughout the literature, with some studies linking perturbations in creatine metabolism to reduced fertility and poor pregnancy outcomes. Maternal dietary creatine supplementation during pregnancy as a safeguard against hypoxia-induced perinatal injury, particularly that of the brain, has also been widely studied in pre-clinical in vitro and small animal models. However, there is still no consensus on whether creatine is essential for successful reproduction. This review consolidates the available literature on creatine metabolism in female reproduction, pregnancy and the early neonatal period. Creatine metabolism is discussed in relation to cellular bioenergetics and de novo synthesis, as well as the potential to use dietary creatine in a reproductive setting. We highlight the apparent knowledge gaps and the research “road forward” to understand, and then utilize, creatine to improve reproductive health and perinatal outcomes.     

A hormonal,physical, and proteomic view of obesity-induced effects on male infertility and possible lifestyle modifications

The increasing incidence of obesity worldwide combined with the parallel trend of declining sperm quality has given rise to the notion that obesity and infertility are linked. While investigations of sperm quality in obese individuals have yielded inconclusive results, studies of the adverse hormonal, physical, and proteomic changes induced by obesity are more definitive. Unfavorable hormonal abnormalities reported in obese males that affect reproduction are decreased levels of testosterone, inhibin B, and ghrelin and increased levels of estrogen, leptin, and resistin. Moreover, erectile dysfunction and elevated scrotal temperatures have been associated with obesity and are important physical barriers to successful male reproduction. Recently, important advances have been made in proteomics and factors have been identified in obese individuals that may impair spermatogenesis and sperm quality. Although obesity contributes to a host of adverse effects on the reproductive system, certain lifestyle modifications can be made to alleviate such effects. Natural weight loss and surgical weight loss have demonstrated favorable results in obese patients by restoring normal hormone levels and reversing the effects of both erectile dysfunction and testicular heat stress. Pharmacological interventions have also proven to be promising in combating the effects of obesity. Particularly, aromatase inhibitors such as anastrozole, letrozole, and testolactone, have been reported to decrease the aromatase over-activity and increased estrogen levels present in obese males. An understanding of abnormalities associated with obesity and possible lifestyle modifications may help clinicians effectively guide their infertile obese male patients and increase fertility rates.     

SPERM MORPHOLOGY AND CHROMATIN CONDENSATION BEFORE AND AFTER SEMEN PROCESSING

Semen analysis constitutes the most important investigation of male infertility. However, the true anomalies present in defective sperm cells have been only partially characterized. The integrity of the sperm chromatin may play the most important role, particularly in ICSI, where most of the natural selection mechanisms are bypassed. This study was carried out to characterize sperm morphology (strict criteria), to evaluate chromatin condensation and sperm count in native semen as well as after semen preparation by the swim-up technique, and to eventually evaluate any correlation between these parameters. Semen from 90 men was analyzed for the above parameters in both the fresh and processed semen. Whereas the sperm count decreased after sperm preparation by the swim-up technique in comparison to the value in the fresh semen (p&lt;.001), there was an increase in the percentage of morphologically normal (p&lt;.001) and chromatin-condensed sperm (p=.99). However, there was no correlation between sperm morphology, chromatin condensation, and sperm count either in the fresh or in the processed semen samples. These results suggest that sperm morphology, sperm count, and chromatin condensation are independent parameters that should be evaluated separately in the assessment of male fertility in an assisted reproduction program.     

雄性生殖系统中瘦素表达及功能的研究进展

男性生育力呈下降趋势,阐明其发生机制有助于男性不育症的精准医疗.瘦素是一种主要由脂肪组织产生的激素,在调节机体能量代谢、参与炎性反应、促进生殖系统发育及维持其正常功能等方面具有重要的作用.瘦素及其受体在哺乳动物下丘脑-垂体-性腺(HPG)轴的内分泌器官、睾丸、生殖道、附属生殖腺以及精子中均有广泛表达,其表达异常与雄性生...     

MOLECULAR BIOLOGY OF MALE INFERTILITY

About 15% of couples have reduced fertility and in approximately one-half of all cases the reason is male infertility, usually of genetic origin. Thus, in the context of research in genes involved in reproduction and sex determination, genetic anomalies in gametogenesis are being extensively studied. The most frequent pathogenic causes of male infertility are Y-chromosomal microdeletions (8-15%) in the long arm of the Y chromosome, which, by loss of specific DNA segments, leads to loss of vital genes for sperm production. Infertile men, who attend infertility clinics, rise to 15% among those with azoospermia or spermatogenesis problem. The new technique of intracytoplasmic sperm injection has allowed many infertile men to achieve their dreams of fatherhood. However, the spermatogenic defect is genetic anomalies, which might be a potential risk of transmitting this defect to future offspring. Therefore, genetic counseling of all couples with the diagnosis of male infertility is recommended before their enrolment in intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection. The important role of genetic abnormalities in the causation of human male infertility is increasingly recognized. While much remains to be learned in this fast-moving field, considerable progress has been made in the clinical delineation of genetic forms of male infertility and in the characterization of the responsible genes and their mutations or deletions. This review should provide insight into the understanding of parthenogenesis of male infertility in the human.     

Flow cytometry applications in the evaluation of sperm quality: semen analysis, sperm function and DNA integrity

Flow cytometry (FCM) has been extensively used to study mammalian sperm in the areas of reproductive toxicology (to monitor effects from environmental, occupational and therapeutic exposures), veterinary science (to preselect the gender of offspring by sorting X- and Y-chromosome-bearing sperm) and clinical andrology (to assess individual fertility potential). Using FCM, a variety of sperm features can now be rapidly measured on a cell-by-cell basis such as sperm count, viability, acrosomal integrity, mitochondrial function and DNA integrity; the last one is involved in postfertilization failure and embryo toxicity. It is foreseen that only a multiplex approach, which includes FCM assays together with the new genomics/proteomics methods, could increase the predictive power of fertility status and help identify susceptible subpopulations of men at risk for infertility, spontaneous abortions and birth defects.     

Agricultural work and male infertility

Data from couples (n = 103) seeking artificial insemination with donor sperm because of poor sperm quality and a control group of couples treated by in-vitro fertilization due to female causes were analysed according to the occupations of the spouses. Comparison of occupational categories revealed a significant difference in the prevalence of agricultural occupation (11/103 vs. 1/103, p<0,01) between the group with male factor infertility and the normospermic controls. These patients also reported more long-term exposure to several insecticides and other pesticides. These toxic chemicals probably have a detrimental effect on male fertility and therefore we suggest more caution in the way they are handled. © 1993 Wiley-Liss, Inc.     

全氟类化合物在人体与动物体内的生殖毒性

全氟类化合物（polyfluorinated chemicals，PFCs）是一类来自工业生产，存在于人们日常生活环境中内分泌干扰物（endocrine disruptors，EDCs）。研究表明，PFCs可以聚集在生物体内，并通过影响甾体激素合成、诱导生殖系统细胞凋亡、拮抗激素受体等机制，在生殖系统表现出毒性作用。在男性中，这类物质被证明与精子的质量与数量的下降及异常精子比率的上调有关，干扰男性性激素水平（如睾酮）；而在女性中也发现血液或卵泡液中PFCs水平的升高，往往伴随着性激素及促性腺激素（如雌孕激素，卵泡刺激素等）水平的异常以及生育力的下降，这类物质在孕期的暴露甚至有影响至下一代的可能。此外，已有动物实验从分子层面对这类物质的毒性机制进行了证实，因此PFCs的生殖毒性值得关注。     

Environmental and Occupational Exposures Associated with Male Infertility

The upsurge in male infertility over the last two decades, possibly due to environmental exposure, has raised significant interest, particularly boosted by reports from fertility clinics, which showed that chronic diseases and hereditary or other medical conditions might only partially explain current incidence of male infertility. Both environmental and occupational settings may have a significant role in exposure to complex mixtures of endocrine disruptors (ED), which play a major role in fertility disorders. The aim of this review is to give an insight into the current knowledge on exposure settings which may be associated with male infertility. Our study relied on a systematic search of PubMed, Scopus, and Web of Science for articles published between January 2000 and September 2020. It showed that some well documented factors associated with male infertility include smoking, and physiological disturbances or chronic diseases such as obesity and diabetes, which in turn, may also reflect lifestyle choices and environmental exposures, especially to EDs such as phthalates, bisphenols, pesticides, and flame retardants. However, the number of studies on the aetiology of male infertility is still too low in comparison with the size of affected population. Occupational health follow-ups and medical surveillance do not collect any data on male infertility, even though ED chemicals are part of many technological processes.Key words: alcohol, bisphenols, diet, electromagnetic fields, endocrine disruptors, obesity, parabens, phthalates, pesticides, smoking, sperm^-