男性育性障碍与联会复合体异常的关系

据有关资料统计,男人中大约有11%育性有障碍,其中由遗传因素引起的男性不育占居首位,包括染色体异常、微小缺失和基因突变等3类。研究表明,男性染色体畸变与精子发生失败或受孕浪费现象密切相关。联会复合体（synaptonemal complex SC）分析为揭示二者之间的关系提供了证据。本文结合近年来SC在男性不育症诊断中的应用和我们在这方面的研究结果,对男性育性障碍与SC异常的关系进行了以下5个方面的评述和讨论。1.XY-二价体与重排染色体联合,干扰或影响X染色体的正常功能,从而干扰精子发生。2. 重排染色体在断裂点处广泛的不配对,引起精子发生失败。3. SC粉碎化、侧生组分膨化、配对紊乱导致精子发生失败。 4. 重排染色体直接的异源配对导致不平衡配子的产生而出现受孕浪费。5.SC蛋白基因的突变引起SC超微结构的变化导致男性不育。     

Variants of the CLOCK gene affect the risk of idiopathic male infertility in the Han-Chinese population

Recent experimental animal studies suggested that the circadian locomotor output cycles kaput protein gene (CLOCK) has been reported to play a critical role in sperm function and male fertility. The aim of this study was to determine whether variants of the CLOCK gene are involved in idiopathic male infertility. The study included 478 idiopathic infertile men and 194 fertile controls who completed physical examinations. Each subject donated 5?ml of peripheral blood and a sample of semen in the ejaculate. An aliquot of each blood sample was used to separate the serum for the measurement of testosterone as well as follicular stimulating hormone (FSH) using the standard radioimmunoassay. The rest of the blood samples was used to extract the DNA for the assay of three tagging single-nucleotide polymorphisms of CLOCK gene, viz., rs1801260, rs3817444 and rs3749474, using the real-time fluorescence quantitative PCR. The ejaculate of each subject was used for semen analysis by computer-assisted semen analysis system. The results indicated: (a) the variant rs1801260 associated with normal semen parameters was linked to a significant increase in the risk of idiopathic infertility, (b) the variant rs3817444 associated with both normal and abnormal semen parameters also indicated an increased risk of idiopathic infertility, and (c) the variants rs3749474 associated with both normal and abnormal semen parameters, on the other hand, conferred no significant risk for male infertility. Furthermore, elevated serum testosterone and FSH levels were correlated with the three variants of CLOCK gene in idiopathic infertility. The findings demonstrate that the human subjects with variants of the CLOCK gene are associated with idiopathic male infertility and therefore may be applied as a risk factor of male infertility.     

Cell-free and intracellular nucleic acids: new non-invasive biomarkers to explore male infertility

Male infertility is a devastating problem that affects many couples worldwide. However, the molecular mechanisms and causes of idiopathic male infertility remain unclear. Circulating cell-free nucleic acids have an important role in human physiology and emerging evidence suggests that they play a role in male infertility. This review summarizes recent results on cell-free and intracellular nucleic acids in male infertility and discusses their potential use as biomarkers of male infertility in the clinical practice.     

Evaluation of <Emphasis Type="Italic">GPx1</Emphasis> Pro198Leu polymorphism in idiopathic male infertility

Infertility is defined as failure to conceive a child after 1 year of unprotected regular sexual intercourse. Approximately half of all cases of infertility are caused by factors related to the male. In nearly 50% of infertile men it is not possible to determine the cause of infertility and this situation has been defined as unexplained or idiopathic. Oxidative stress plays an important role in the pathophysiology of male infertility. Oxidative stress results from an imbalance in free radicals and antioxidant defense mechanisms of the body. Genetic variations in the antioxidant gene coding for GPx enzyme may lead to decreased or impaired regulation of its enzymatic activity and alter reactive oxygen species (ROS) detoxification. We have investigated the possible association between polymorphism GPx1 Pro198Leu and idiopathic male infertility. One hundred patients with idiopathic male infertility and one hundred fifty healthy volunteers were enrolled. Genomic DNA was extracted from blood samples. Genotyping for the GPx1 Pro198Leu polymorphism was done by PCR–restriction fragment length polymorphism (RFLP) using ApaI. The genotype frequencies were 11% (Leu/Leu), 76% (Pro/Leu) and 13% (Pro/Pro) in the patient group and 8.7% (Leu/Leu), 67.3% (Pro/Leu) and 24% (Pro/Pro) in the control group. The genotype and allele frequencies of GPx1 Pro198Leu did not differ between the patient group and the control group (P = 0.09 and P = 0.1, respectively). In conclusion, there is no correlation between idiopathic male infertility and the GPx1 codon Pro198Leu polymorphism. Further studies are needed to investigate other genetic factors that influence the development of idiopathic male infertility.     

The Cytochrome P4501A1 gene polymorphisms and idiopathic male infertility risk: A meta-analysis

Studies of the relationship between male infertility and CYP1A1 polymorphisms are inconclusive. To drive a more precise estimation, we performed a meta-analysis based on 1060cases and 1225 controls from 7 published case–control studies. PubMed and CNKI literature search were conducted to identify all eligible studies investigating such a relationship. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the additive model, dominant model, recessive model, and allele-frequency genetic model. In the overall analysis, the frequency of CYP1A1*2A genotype was significantly associated with susceptibility to idiopathic male infertility. Further stratified analysis by ethnicity showed notable association between the polymorphism and the risk of idiopathic male infertility in Asians. In conclusion, these results support that the CYP1A1*2A genotype polymorphism mainly contributes to idiopathic male infertility susceptibility in Asians but not in Caucasians.     

体外受精-胚胎移植女性患者焦虑状况的影响因素分析及对妊娠结局的影响

摘要 目的：探讨体外受精-胚胎移植（IVF-ET）女性患者焦虑状况的影响因素及对妊娠结局的影响。方法：选择2019年3月~2021年4月期间南京鼓楼医院生殖医学科收治的192例IVF-ET女性患者。采用焦虑自评量表（SAS）评估所有患者焦虑状况。收集患者的临床资料,单因素及多因素Logistic回归分析IVF-ET女性患者焦虑的影响因素。观察不同焦虑状况患者的妊娠结局。结果：192例IVF-ET女性患者中,有37例（19.27%）患者出现焦虑状况。其中轻度焦虑15例（40.54%）、中度焦虑10例（27.03%）、重度焦虑12例（32.43%）。单因素分析结果显示,IVF-ET女性患者是否焦虑与家庭月收入、辅助生殖技术治疗失败史、文化程度、职业、不孕年限、年龄、社会支持、不孕类型、不孕原因有关（P<0.05）。多因素Logistic回归分析结果显示：不孕类型为原发不孕、不孕原因为女方因素、年龄>34岁、家庭月收入<3000元、文化程度为高中或中专及以下是导致IVF-ET女性患者发生焦虑的危险因素（P<0.05）。无焦虑患者优胚例数、2PN受精例数、获卵例数、临床妊娠例数占比均高于焦虑患者（P<0.05）。结论：IVF-ET女性患者较易产生焦虑情绪,其焦虑状况受不孕类型、不孕原因、年龄、家庭月收入、文化程度影响,且焦虑状况还会影响患者的妊娠结局,临床工作中应对存在上述影响因素的患者进行积极心理疏导。     

The role of oocyte in the genetic determinations of fertility and infertility

Oocyte specific genes play important role in the foliculogenesis, ovulation, fertilization and early embryogenesis. It is suggested that 17-20% of infertility in both sex has idiopathic aspect. This kind of infertility is mainly associated with genetic background. The study on the role of oocyte specific genes can help in our understanding of the causes of idiopathic infertility.     

Genetisch bedingte Entwicklungsstörungen der Genitalwege

Anomalies of the female and male genital tracts can be the cause of sterility and infertility. In this review disorders of the Mullerian and Wolffian structures which are responsible for the development of male and female genital tracts will be discussed.     

Fécondation assistée par micro injection des spermatides: Etat des lieux et questions posées

In order to treat male infertility, since 5 years ago, intracytoplasmic sperm injection (ICSI) represents a new therapeutic approach of different forms of male sterility including obstructive and spermatogenic failure azoospermia. This paper reviews the use of ICSI with round or elongated spermatids.     

Genetics of hybrid incompatibility between Lycopersicon esculentum and L. hirsutum

We examined the genetics of hybrid incompatibility between two closely related diploid hermaphroditic plant species. Using a set of near-isogenic lines (NILs) representing 85% of the genome of the wild species Lycopersicon hirsutum (Solanum habrochaites) in the genetic background of the cultivated tomato L. esculentum (S. lycopersicum), we found that hybrid pollen and seed infertility are each based on 5-11 QTL that individually reduce hybrid fitness by 36-90%. Seed infertility QTL act additively or recessively, consistent with findings in other systems where incompatibility loci have largely been recessive. Genetic lengths of introgressed chromosomal segments explain little of the variation for hybrid incompatibility among NILs, arguing against an infinitesimal model of hybrid incompatibility and reinforcing our inference of a limited number of discrete incompatibility factors between these species. In addition, male (pollen) and other (seed) incompatibility factors are roughly comparable in number. The latter two findings contrast strongly with data from Drosophila where hybrid incompatibility can be highly polygenic and complex, and male sterility evolves substantially faster than female sterility or hybrid inviability. The observed differences between Lycopersicon and Drosophila might be due to differences in sex determination system, reproductive and mating biology, and/or the prevalence of sexual interactions such as sexual selection.     

DISSECTING THE GENETIC ARCHITECTURE OF F1 HYBRID STERILITY IN HOUSE MICE

Hybrid sterility as a postzygotic reproductive isolation mechanism has been studied for over 80 years, yet the first identifications of hybrid sterility genes in Drosophila and mouse are quite recent. To study the genetic architecture of F₁ hybrid sterility between young subspecies of house mouse Mus m. domesticus and M. m. musculus, we conducted QTL analysis of a backcross between inbred strains representing these two subspecies and probed the role of individual chromosomes in hybrid sterility using the intersubspecific chromosome substitution strains. We provide direct evidence that the asymmetry in male infertility between reciprocal crosses is conferred by the middle region of M. m. musculus Chr X, thus excluding other potential candidates such as Y, imprinted genes, and mitochondrial DNA. QTL analysis identified strong hybrid sterility loci on Chr 17 and Chr X and predicted a set of interchangeable autosomal loci, a subset of which is sufficient to activate the Dobzhansky–Muller incompatibility of the strong loci. Overall, our results indicate the oligogenic nature of F₁ hybrid sterility, which should be amenable to reconstruction by proper combination of chromosome substitution strains. Such a prefabricated model system should help to uncover the gene networks and molecular mechanisms underlying hybrid sterility.     

Y-haplotypes and idiopathic male infertility in an Indian population

Infertility being a multifactorial disorder, both genetic and environmental factors contribute to the etiology of infertile phenotype. Chromosomal anomalies and Y-microdeletion are the established genetic risk factors of male infertility. Y-haplotypes has been found as risk factor for male infertility in certain populations, though in certain others no association has been reported, suggesting a population-specific association of these variations with male infertility. In a case-control study, 165 azoo-/oligospermic patients and 200 controls were haplotyped for certain Y-haplogroups for a possible association with idiopathic male infertility in an Indian population. Analysed Y-haplogroups showed no association with infertile phenotype. Thus this genetic factor is not a risk for infertility in the studied Indian population but that does not rule out the possibility of any of them, to be a risk in other populations.     

Molecular insights into the causes of male infertility

Infertility is a reproductive health problem that affects many couples in the human population. About 13–18% of couple suffers from it and approximately one-half of all cases can be traced to either partner. Regardless of whether it is primary or secondary infertility, affected couples suffer from enormous emotional and psychological trauma and it can constitute a major life crisis in the social context. Many cases of idiopathic infertility have a genetic or molecular basis. The knowledge of the molecular genetics of male infertility is developing rapidly, new “spermatogenic genes” are being discovered and molecular diagnostic approaches (DNA chips) established. This will immensely help diagnostic and therapeutic approaches to alleviate human infertility. The present review provides an overview of the causes of human infertility, particularly the molecular basis of male infertility and its implications for clinical practice.     

Function of RAD6B and RNF8 in spermatogenesis

Histone ubiquitination regulates sperm formation and is important for nucleosome removal during spermatogenesis. RNF8 is an E3 ubiquitin ligase, and RAD6B is an E2 ubiquitin-conjugating enzyme. Both proteins participate in DNA damage repair processes via histone ubiquitination. Loss of RNF8 or RAD6B can lead to sterility in male mice. However, the specific mechanisms regulating these ubiquitin-mediated processes are unclear. In this study, we found that RNF8 knockout mice were either subfertile or sterile based on the numbers of offspring they produced. We explored the mechanism by which RAD6B and RNF8 knockouts cause infertility in male mice and compared the effects of their loss on spermatogenesis. Our results demonstrate that RAD6B can polyubiquitinate histones H2 A and H2B. In addition, RNF8 was shown to monoubiquitinate histones H2 A and H2B. Furthermore, we observed that absence of histone ubiquitination was not the only reason for infertility. Senescence played a role in intensifying male sterility by affecting the number of germ cells during spermatogenesis. In summary, both histone ubiquitination and senescence play important roles in spermatogenesis.     

Association between 3801T>C Polymorphism of CYP1A1 and Idiopathic Male Infertility Risk: A Systematic Review and Meta-Analysis

Background

Epidemiological studies have evaluated the association between 3801T>C polymorphism of CYP1A1 gene and the risk for idiopathic male infertility, but the results are inconclusive. We aimed to derive a more precise estimation of the relationship by conducting a meta-analysis of case-control studies.

Methods

This study conformed to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase and CNKI databases were searched through November 2013 to identify relevant studies. Pooled odds ratios with 95% confidence intervals were used to assess the strength of the association between CYP1A1 3801T>C polymorphism and idiopathic male infertility risk. Q-test was performed to evaluate between-study heterogeneity and publication bias was appraised using funnel plots. Sensitivity analyses were conducted to evaluate the robustness of meta-analysis findings.

Results

Six studies involving 1,060 cases and 1,225 controls were included in this meta-analysis. Overall, significant associations between 3801T>C polymorphism and idiopathic male infertility risk were observed in allelic comparison (OR = 1.36, 95% CI: 1.01–1.83), homozygous model (OR = 2.18, 95% CI: 1.15–4.12), and recessive model (OR = 1.86, 95% CI: 1.09–3.20), with robust findings according to sensitivity analyses. However, subgroup analyses did not further identify the susceptibility to idiopathic male infertility in all comparisons. Funnel plot inspections did not reveal evidence of publication bias.

Conclusions

The current meta-analysis provides evidence of a significant association between CYP1A1 3801T>C polymorphism and idiopathic male infertility risk. Considering the limitation inherited from the eligible studies, further confirmation in large-scale and well-designed studies is needed.     

精子端粒长度与特发性男性不育相关

端粒是真核生物染色体末端的多功能特异性DNA-蛋白结构,覆盖在染色体末端,保护基因组的稳定性。端粒在减数分裂过程中起到了十分重要的作用,协助染色体配对、联会、同源重组和分离。精子中的端粒可能在精子的受精能力和胚胎发育中起到重要作用。近年来,端粒与生殖的相关性研究成为一个新的热点,但精子端粒与男性不育间的相关性并不明确。本文采用实时荧光定量PCR方法检测中国特发性男性不育人群(126例)和正常可育男性人群(138例)的精子相对端粒长度,结果发现,特发性男性不育病例的精子平均相对端粒长度(2.894±0.115)低于正常对照组(4.016±0.603),差异具有统计学意义(P=5.097×10^-5);并且精子相对端粒长度与精子密度、精子总数和精子活力都有显著的相关性：精子数量较多和/或精子活力较高,精子相对端粒长度较长。研究结果提示,在中国人群中,精子端粒长度与特发性男性不育具有相关性,精子的端粒长度可能影响精子发生和精子的功能,精子端粒的缩短导致精子数目及活力的降低从而导致男性不育。     

Hybrid male sterility in rice is due to epistatic interactions with a pollen killer locus

In intraspecific crosses between cultivated rice (Oryza sativa) subspecies indica and japonica, the hybrid male sterility gene S24 causes the selective abortion of male gametes carrying the japonica allele (S24-j) via an allelic interaction in the heterozygous hybrids. In this study, we first examined whether male sterility is due solely to the single locus S24. An analysis of near-isogenic lines (NIL-F(1)) showed different phenotypes for S24 in different genetic backgrounds. The S24 heterozygote with the japonica genetic background showed male semisterility, but no sterility was found in heterozygotes with the indica background. This result indicates that S24 is regulated epistatically. A QTL analysis of a BC(2)F(1) population revealed a novel sterility locus that interacts with S24 and is found on rice chromosome 2. The locus was named Epistatic Factor for S24 (EFS). Further genetic analyses revealed that S24 causes male sterility when in combination with the homozygous japonica EFS allele (efs-j). The results suggest that efs-j is a recessive sporophytic allele, while the indica allele (EFS-i) can dominantly counteract the pollen sterility caused by S24 heterozygosity. In summary, our results demonstrate that an additional epistatic locus is an essential element in the hybrid sterility caused by allelic interaction at a single locus in rice. This finding provides a significant contribution to our understanding of the complex molecular mechanisms underlying hybrid sterility and microsporogenesis.     

Etiologie de 350 cas de stérilité masculine. Effet de divers traitements sur la qualité du sperme et analyse de leur rôle dans la survenue de 100 grossesses

Etiologic factors of male sterility and the effect of different treatments on sperm quality have been evaluated in 350 men consulting for primary or secondary infertility of more than one year. Environmental factors represent 12% of the etiologies, acquired diseases such as varicoele and prostatitis 36.8%, testicular failure 23%, endocrinopathy 1,4%, sexual dysfunction 1,4%, abnormality of sperm transport 7,4%. and idiopathic cases 19%. A conventionnal treatment has been tempted in 50% of the cases and evaluated in 101 patients. A normalisation of the sperm (defined by a total motile sperm count (TMS) higher than 16 millions) has been observed in a variable proportion of the cases: 80% after hormonotherapy, 37% after varicocelectomy, and 30% after antiinflammatory treatment. Among 100 pregnancies, 39% occurred either spontanously or after ovulation induction, 32% after classical andrological treatment and 26% after assisted reproductive techniques (ART) such as in vitro fertilization, intracytoplasmic sperm injection or intrauterine insemination. The efficiency of these different treatments according to the TMS and the utility of the clinical investigation of the infertile male are discussed. The risk faced by the wife because of ART are underlined.     

Glutathione S-transferases gene polymorphisms and risk of male idiopathic infertility: a systematic review and meta-analysis

The Glutathione S-transferases (GSTs) polymorphisms have been implicated in susceptibility to male idiopathic infertility, but study results are still controversial. To investigate the genetic associations between GSTs polymorphisms and risk of male idiopathic infertility, a systematic review and meta-analysis were performed. Meta-analysis was performed by pooling odds ratio (OR) with its corresponding 95 % confidence interval (95 % CI) form studies in electronic databases up to March 16, 2012. Glutathione S-transferase M 1 (GSTM1) null genotype, Glutathione S-transferase T 1 (GSTT1) null genotype, and dual null genotype of GSTM1/GSTT1 were analyzed independently. 14 eligible studies with a total of 1,845 idiopathic infertility males and 1,729 controls were included. There were 13 studies on GSTM1 polymorphism, 10 ones on GSTT1 polymorphism and 5 ones on GSTM1-GSTT1 interaction analysis. Meta-analyses of total relevant studies showed GSTM1 null genotype was significantly associated with an increased risk of male idiopathic infertility (OR = 1.40, 95 % CI 1.07–1.84, P _OR = 0.015). The GSTM1-GSTT1 interaction analysis showed dual null genotype of GSTM1/GSTT1 was also significantly associated with increased risk of male idiopathic infertility (OR = 1.85, 95 % CI 1.07–3.21, P _OR = 0.028). Subgroup analyses by ethnicity showed the associations above were still statistically significant in Caucasians (For GSTM1, OR = 1.51, 95 % CI 1.11–2.05, P _OR = 0.009; For GSTM1/GSTT1, OR = 2.10, 95 % CI 1.51–2.91, P _OR < 0.001). This meta-analysis suggests GSTM1 null genotype contributes to increased risk of male idiopathic infertility in Caucasians, and males with dual null genotype of GSTM1/GSTT1 are particularly susceptible to developing idiopathic infertility.     

SPANX蛋白的研究进展及其与男性生育力的相关性

男性不育症病因十分复杂,遗传、环境、内分泌等许多因素都会导致男性不育。而现今临床上多依据精液常规分析对男性不育做出诊断和治疗,但仅依赖精液常规参数存在一定局限性。探寻男性生育力的潜在生物标志分子是当前男性不育的迫切需求。精子X染色体核结合精子蛋白(The sperm protein associated with the nucleus on the X chromosome,SPANX)是在精子中表达的一类小分子蛋白,SPANX蛋白家族基因定位在X染色体上,它随精子的成熟而迁徙,参与精子结构的形成,在精子成熟的不同时期,蛋白定位和蛋白表达均存在差异。在精液参数正常的不育男性和自发弱精症的男性中,SPANX表达下调;同时在活性氧自由基(reactive oxygen species,ROS)阴性的精子中,SPANXC表达降低,在DNA碎片率低的精子中,SPANX表达增高;这些表明SPANX与男性生育力存在一定的相关性,但其与生育力的影响极其相关机制还需要进一步的研究。