Another functional frame‐shift polymorphism of DEFB126 (rs11467497) associated with male infertility

DEFB126 rs140685149 mutation was shown to cause sperm dysfunction and subfertility. Indel rs11467497 is another 4‐nucleotide frame‐shift mutation (151bp upstream of rs140685149) that leads to the premature termination of translation and the expression of peptide truncated at the carboxyl terminus. In the present study, we performed a comprehensive association study to check the contribution of rs140685149 and rs11467497 to male infertility. Our results confirmed the previous findings that there was no association between rs140685149 and sperm motility. In contrast, we found a significant association of another indel rs11467497 with male infertility. Moreover, rs11467497 was shown to be associated with higher number of round cells in the infertile males with low sperm motility. Surprisingly, the two mutations commonly existed in the sperm donors (n = 672), suggesting a potential application of the two indels in the screening for eligible sperm donors. Western blotting assays showed the sperms with rs140685149 2‐nt deletion tended to have unstable DEFB126 protein in contrast of no DEFB126 protein expressed in the sperms with rs11467497 4‐nt deletion, suggesting a more severe consequence caused by rs11467497 mutation. In conclusion, our study presented a significant contribution of another functional frame‐shift polymorphism of DEFB126 (rs11467497) to male infertility.     

腹腔镜与宫腔镜联合治疗输卵管性不孕症患者的疗效观察

目的：探讨腹腔镜与宫腔镜联合治疗输卵管性不孕症的临床效果。方法：收集2012 年1 月-2014年1 月我院收治的68 例输 卵管性不孕症患者,按照随机字数表法将患者随机分为观察组（腹腔镜联合宫腔镜治疗）与对照组（单纯宫腔镜治疗）各34例。对 比两组临床指标及术后一年输卵管再通率、妊娠率及并发症发生率。结果：两组各临床指标对比,差异无统计学意义（P>0.05）;观 察组输卵管再通率和妊娠率分别为91.17%,85.29%,显著高于对照组的73.53%、52.94%,而并发症发生率为11.76%,低于对照组 的32.35%,差异均有统计学意义（均P<0.05）。结论：腹腔镜联合宫腔镜治疗输卵管性不孕症切口小,术后恢复快,能有效提高卵管 再通率和妊娠率,减少术后并发症,值得临床推广。     

Impact of precise modulation of reactive oxygen species levels on spermatozoa proteins in infertile men

Background

Elevated levels of reactive oxygen species (ROS) are detected in 25% to 80% of infertile men. They are involved in the pathology of male infertility. Understanding the effect of increasing levels of ROS on the differential expression of sperm proteins is important to understand the cellular processes and or/pathways that may be implicated in male infertility. The aim of this study was to examine differentially expressed proteins (DEPs) in spermatozoa from patients with low, medium and high ROS levels.

Methods

A total of 42 infertile men presenting for infertility and 17 proven fertile men were enrolled in the study. ROS levels were measured by chemiluminescence assay. Infertile men were divided into Low (0- < 93 RLU/s/10⁶ sperm) (n = 11), Medium (>93-500 RLU/s/10⁶ sperm) (n = 17) and High ROS (>500 RLU/s/10⁶ sperm) group (n = 14). All fertile men had ROS levels between 4-50 RLU/s/10⁶ sperm. 4 subjects from fertile group and 4 each from the Low, Medium and High ROS were pooled. Protein extraction, protein estimation, gel separation of the proteins, in-gel digestion, LTQ-orbitrap elite hybrid mass spectrometry system was conducted. The DEPs, the cellular localization and pathways of DEPs involved were examined utilizing bioinformatics tools.

Results

1035 proteins were identified in the 3 groups by global proteomic analysis. Of these, 305 were DEPs. 51 were unique to the Low ROS group, 47 Medium ROS group and 104 were unique to the High ROS group. 6 DEPs were identified by Uniprot and DAVID that had distinct reproductive functions and they were expressed only in 3 ROS groups but not in the control.

Conclusions

We have for the first time demonstrated the presence of 6 DEPs with distinct reproductive functions only in men with low, medium or high ROS levels. These DEPs can serve as potential biomarkers of oxidative stress induced male infertility.

Electronic supplementary material

The online version of this article (doi:10.1186/1559-0275-12-4) contains supplementary material, which is available to authorized users.     

The evolution of infertility: does hatching rate in birds coevolve with female polyandry?

Natural levels of infertility in many taxa are often remarkably high, amounting to a considerable fitness cost which one expects to be minimized by natural selection. Several mechanisms have been proposed as potential causes of infertility, including inbreeding depression, genetic incompatibilities and selfish genetic elements. Infertility may also be an inherent result of conflict over fertilization between the sexes in polyandrous species, either because too many sperm enter the egg or because of over‐efficient barriers to such polyspermic fertilizations. We generated phylogenetic independent contrasts to examine the variation in hatching success for a maximum of 58 species of birds in relation to two measures of female polyandry. Hatching success varied enormously across species (range: 61–100%), with a mean of 12% of eggs failing to hatch, but was not related to either the rate of extrapair paternity or to relative testes size. Thus, the causes of this significant fitness cost remains unclear and merits further examination by evolutionary biologists.     

Biochemical changes in cervical mucus-factor infertility

Cervical-factor infertility has generally been attributed to the presence of antispermatozoal antibodies in the secretions of the uterine cervix, despite the fact that the incidence of sperm-specific antibodies in these women is generally low. We report here a modification in the structure of the cervical mucus of patients with a diagnosed cervical factor. Cervical mucus from patients with a cervical factor of nonimmunological origin, collected during the periovulatory phase of the menstrual cycle, had (1) a significant decrease in the content of glycosidically bound sialic acid and (2) an increased ability to act as an acceptor for sialic acid from cytidine-5′-monophospho-N-acetylneuraminic acid (CMP-sialic acid) when incubated with an exogenous sialyltransferase; in comparison to mucus from normal fertile women. Both siaiyltransferase and fucosyltransferase activities were detected in cervical mucus, but there was no difference between fertile normal and cervical-factor patients using the assays described. These results reinforce a possible role for sialic acid residues and their associated glycosyltransferases in the regulation of spermatozoal–cervical mucus interaction.     

Male infertility, female fertility and extrapair copulations

Females that are socially bonded to a single male, either in a social monogamy or in a social polygyny, are often sexually polyandrous. Extrapair copulations (EPC) have often been suggested or rejected, on both empirical and theoretical grounds, as an important mechanism that enables females to avoid fertility risks in case their socially bonded male is infertile. Here, we explore this possibility in two steps. First, we present a mathematical model that assumes that females have no precopulatory information about male fertility, and shows that a female EPC strategy increases female reproductive success only if certain specific conditions are upheld in the nature of male infertility. In particular, these conditions require both (i) that fertile sperm precedence (FSP) is absent or incomplete within ejaculates of the same male (i.e. that an infertile male is, at least partly, truly infertile), and (ii) the existence of FSP among ejaculates of different males (such that infertile spermatozoa of the infertile male are at a disadvantage when competing against spermatozoa of a fertile male). Second, to evaluate their potential role in the evolution of female EPC, we review the abundance and FSP patterns of the different male infertility types. The conclusion is drawn that some common infertility types, such as poor sperm count or motility, contribute to the evolution of female EPC, whereas other common infertility types, such as sperm depletion or allocation in a social monogamy (but not in a social polygyny), and in particular male driven polyspermy, do not. Also, a deeper look at the arms race between sperm fertilization efficiency and female barriers to sperm may answer the non‐trivial question: “why are some types of infertility so common?”     

精子DNA甲基化异常与男性不育

DNA甲基化／去甲基化是表观遗传学最重要的内容并可以控制基因的表达和印迹,越来越多的研究显示DNA甲基化异常与不育男性精子发生异常、特定肿瘤的发生、神经系统疾病、Rett综合征等有关。文章通过总结近来的相关研究资料来阐述精子发生过程中的DNA甲基化状态的改变,探讨精子DNA的甲基化异常与男性不育之间的联系,旨在为男性不育的治疗提供新的临床思路。     

Chromosomal Abnormality and Y Chromosome Microdeletion in Chinese Patients with Azoospermia or Severe Oligozoo-spermia

Chromosomal abnormality and Y chromosome microdeletion are regarded as two frequent genetic causes associated with spermatogenic failure in Caucasian population. To investigate the distribution of the two genetic defects in Chinese patients with azoospermia or severe oligozoospermia, karyotype analysis by G-banding was carried out in 358 idiopathic infertile men, including 256 patients with azoospermia and 102 patients with severe oligozoospermia, and screening of AZF region microdeletion of Y chromosome by multiplex PCR was performed in those patients without detectable chromosomal abnormality and 100 fertile controls. Of 358 patients, 39(10.9%) were found to have chromosomal abnormalities in which Klinefelters syndrome (47, XXY) was the most common chromosomal aberration. The incidence of sex chromosomal abnormality in patients with azoospermia was significantly higher than that in patients with severe oligozoospermia (12.1% vs 1%). Among the rest of the 319 patients with normal karyotype, 46 (14.4%) were found to have microdeletions in AZF region. The prevalence rates of AZF microdeletion was 15% and 13.1% in patients with azoospermia and severe oligozoospermia respectively. The microdeletion in AZFc was the most frequent deletion and all the microdeletions in AZFa were found in azoospermic patients. No microdeletion in AZF region was detected in fertile controls. In conclusion, chromosomal abnormality and AZF region microdeletion of Y chromosome might account for about 25% of Chinese infertile patients with azoospermia or severe oligozoospermia, suggesting the two abnormalities are important genetic etiology of spematogenic failure in Chinese population and it is essential to screen them during diagnosis of male infertility before in vitro assisted fertilization by introcytoplasmic sperm injection.     

中国无精症、严重寡精症患者的染色体异常和Y染色体微缺失

染色体异常和Y染色体微缺失被认为是两个白种人群中常见的生精障碍相关遗传因素。为了解中国无精症、严重寡精症患者中的染色体异常和Y染色体微缺失,运用染色体G显带技术,在358个原发无精症（256人）和严重寡精症（102人）不育患者中进行染色体核型分析;同时运用多重PCR技术,在核型正常的患者和100个正常生育男性中,对Y染色体AZF区微缺失进行筛查。在358个患者中,39人（10．9％）发现有染色体异常,Klinefelter（47,XYY）最为常见。无精症患者性染色体异常频率明显高于严重寡精症患者（12．1％VS1％）。在319个核型正常的患者中,46（14．4％）发现有AZF区微缺失,无精症和寡精症患者中Y染色体微缺失频率分别为15％和13．1％,AZFc区的微缺失最为常见,AZFa区的微缺失只见于无精症患者,正常生育男性中未发现AZF区的微缺失。结果显示,在中国无精症、严重寡精症患者中,大约25％的患者有染色体异常或Y染色体AZF区微缺失,提示这两种遗传异常是中国人群生精障碍的重要相关遗传病因,有必要在男性不育的诊断以及利用细胞浆内精子注射技术进行辅助生育时,对患者的这些遗传异常进行筛查。     

Obesity Increases the Risk of Spontaneous Abortion during Infertility Treatment

Objective: This study examines the relationship between body mass and the risk of spontaneous abortion in a large cohort of patients who received infertility treatment. Research Methods and Procedures: This is a retrospective study using data on pregnancies (n = 2349) achieved after treatment in a tertiary medical center from 1987 to 1999. One pregnancy per subject was included, and the subjects were stratified into five body mass groups based on body mass index (BMI): underweight, <18.5 kg/m²; normal, 18.5 to 24.9 kg/m²; overweight, 25 to 29.9 kg/m²; obese, 30 to 34.9 kg/m²; and very obese, ≥35 kg/m². Logistical regression analysis was used. Results: The overall incidence of spontaneous abortion was 20% (476 of 2349). The effect of BMI on the risk of spontaneous abortion was significant after adjusting for several independent risk factors. Compared with the reference group (BMI 18.5 to 24.9 kg/m²), underweight women had a similar risk of spontaneous abortion, whereas there was progressive increase of risk in overweight, obese, and very obese groups (p < 0.05, p < 0.01, and p < 0.001, respectively). Discussion: Of all known risk factors for spontaneous abortion, the control of obesity has great significance because it is noninvasive, potentially modifiable, possibly amenable to low cost, and self‐manageable by patients. This study established a positive relationship between BMI and the risk of spontaneous abortion in women who became pregnant after assisted reproductive technology treatment.