Defending male fertility

An estimated 10 to 15% of couples suffer from infertility, and many treatment decisions rely on trial and error. In this issue of Science Translational Medicine, Tollner and colleagues provide strong evidence from a human genetics study that a common variant in the beta defensin 126 gene, the "del" variant, can reduce male fertility substantially. In addition, they show a plausible mechanism for reduced fertility: Sperm from del/del homozygotes lack an important component of their glycoprotein coat and have difficulty penetrating a surrogate for cervical mucus. If replicated in future studies, these findings promise to guide choices about the timing and type of assisted reproduction interventions-and further hint at the possibility of treating sperm from del/del homozygotes to promote fertility.     

Clock基因对雄性小鼠生殖功能影响

目的:通过干扰小鼠睾丸精子节律基因Clock的表达,研究Clock对雄性小鼠生殖能力的影响。方法:通过RNAi技术,向小鼠睾丸注射Clock干扰质粒干扰雄性小鼠睾丸节律基因Clock的表达。研究干扰Clock基因后精子数量、精子活力、体外受精率和雌鼠胎仔数变化,以及对精子顶体内透明质酸酶活性、芳香基硫酸酯酶A的含量影响。结果:Clock干扰质粒在体内可影响雄性小鼠的胎仔数,但注射干扰质粒后小鼠精子计数、精子活力及体外授精率无明显变化,精子顶体内透明质酸酶活性和芳香基硫酸酯酶A含量也无明显变化。结论:节律基因Clock与雄性小鼠生殖能力有密切关系。     

囊性纤维变性跨膜调节器基因突变对男性生殖的影响

1　ＣＦＴＲ基因突变及主要症状囊性纤维变性跨膜调节器 (ｃｙｓｔｉｃｆｉｂｒｏｓｉｓｔｒａｎｓ ｍｅｍｂｒａｎｅｃｏｎｄｕｃｔａｎｃｅｒｅｇｕｌａｔｏｒ,ＣＦＴＲ)基因于 1989年被发现 ,位于人的第 7染色体上。其编码的蛋白是一种膜蛋白 ,这种跨膜蛋白是一个Ｃｌ- 离子通道蛋白 ,受ｃＡＭＰ的调控。正常的ＣＦＴＲ由 14 80个氨基酸组成 ,含有两个结构区 ,每个结构区含有 6个跨膜片段[1] ,由称为Ｒ -结构域的多肽链连接 ,Ｒ -结构域上有大量的磷酸化位点 ,还有两个核苷酸结合位点(ｎｕｃｌｅｏｔｉｄｅｂｉｎｄｉｎｇｆｏｌｄｓ ,Ｎ…     

CFTR gene mutations in sarcoidosis

Sarcoidosis is a complex disease of multiorgan granulomatous inflammation. Genetic susceptibility is involved in the pathogenesis of the disorder. Two successive studies from Italy have shown a high frequency of mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in patients suffering from sarcoidosis. We have genotyped a panel of 63 families with two or more affected siblings for the CFTR gene mutation R75Q, which was found to be present in three of 26 cases of the Italian study. Although R75Q was present in seven families, it was neither associated with the sarcoidosis phenotype in the German population (P=0.5), nor was it linked to sarcoidosis (P=0.54). In addition, a screening for 34 functional CFTR mutations was performed in a subset of 54 patients from 25 families. These patients were known to be concordant for at least one parental copy of the CFTR gene. With the exception of the mayor CF mutation deltaF508, which was present in three patients and absent in one patient from two families, we did not find any other CF mutation in these 54 patients. Our results do not support the hypothesis that CFTR mutations have a major influence on the pathogenesis of sarcoidosis.     

Traffic pollutants affecting male fertility

Dear Sir, De Rosa et al. (2003) have documented an inverse associationbetween traffic pollutants and the semen parameters (viz., spermmotility, sperm kinetics and sperm function) in toll-gate workerswith the environmental levels of sulphur oxide (SO), nitrogenoxide (NO), carbon monoxide (CO) and lead (Pb)     

Prostasomes--their effects on human male reproduction and fertility

The prostate is a glandular male accessory sex organ vital fornormal fertility. It provides the prostatic component of seminalplasma which nourishes and protects sperm following ejaculation.Prostasomes are small (40–500 nm) membrane-bound vesiclesproduced by epithelial cells lining the prostate acini and area component of prostatic secretions. Although the existenceof these particles has been known for many years, their fullfunction and relevance to reproductive health are largely unknown.Proteomic studies have shown a wide range of proteins (enzymes,structural proteins and novel, unannotated proteins) presentin or on the surface of prostasomes providing them with a diversenature. Interestingly prostasomes are able to fuse with sperm,this event and the associated transfer of proteins lies at theheart of many of their proposed functions. Sperm motility isincreased by the presence of prostasomes and their fusion preventspremature acrosome reactions. Prostasomes have been shown toaid protection of sperm within the female reproductive tractbecause of immunosuppressive, antioxidant and antibacterialproperties. Clinically these functions imply a role for prostasomesin male factor infertility. However, the very functions thatpromote fertility may have negative connotations in later life;recent work has suggested that prostasomes are involved in prostatecancer. Clearly more work is needed to clarify the role of thesenovel particles and their impact on men’s health.     

N-ethyl-N-nitrosourea (ENU) mutagenesis and male fertility research

Male infertility affects about 1 in 25 men in the western world. Conversely, there is an urgent requirement for additional male-based contraceptives, yet progress in both areas has been severely hampered by a lack of knowledge of the biochemistry and physiology of male reproductive function. It is only through a thorough knowledge of these processes that we can hope to insightfully regulate male reproductive function. Without doubt, mouse models will form an important foundation in any future process. In recent years, the chemical mutagen N-ethyl-N-nitrosourea (ENU) has been used widely to identify genes essential for a range of biological systems including male infertility. These studies have shown random mutagenesis is an attractive means of identifying key genes for male fertility. This technique has distinct, but complementary advantages compared to knockout technologies. Specifically, it allows the removal of researcher bias whereby only pre-conceived genes are tested for function; it produces mice with a guaranteed phenotype and allows for the production of allelic series of mice to dissect all aspects of gene function. ENU mouse mutagenesis programs will enable advances in the diagnosis and treatment of human male infertility and ultimately aid in the development of novel male-based contraceptives.     

Variations of the CFTR gene in the Hanoi-Vietnamese

In order to investigate polymorphic backgrounds of the cystic fibrosis transmembrane conductance regulator gene (CFTR) in the Vietnamese, we analyzed 495 blood samples of randomly selected healthy individuals in Hanoi for the delta F508 mutation and TG-repeats, poly-T, and M470V polymorphisms. We compared their distributions with those of Caucasians and other Asian populations. No delta F508 mutation was found, being consistent with the extremely low incidence of cystic fibrosis (CF) in Vietnam. Allele frequency of the T5 allele promoting exon 9 skipping was 0.037. Greater number of TG-repeats, which is known to facilitate this aberrant splicing, was a predominant trend in the Vietnamese and other Asians. A "T5-TG12-V470" haplotype was most common (29/37) among T5-bearing haplotypes. Three major haplotypes, T7-TG12-M470, T7-TG11-V470, and T7-TG12-V470, estimated by PHASE program, related to 92% of the population. This is the first study of the CFTR gene among the Vietnamese.     

The flow cytometry for diagnosis of male fertility

The patient came with a severe testicular disturbance (oligoasthenoteratozoospermia) into the department of andrology. After antiphlogistic- and antiestrogen therapy the clinical spermatological findings (spermiograms) were compared with the corresponding histograms of the flow cytometry analysis and interpreted as according with them.     

Impact of trisomy on fertility and meiosis in male mice

BACKGROUND: Chromosomal abnormalities frequently are associated with impairment or arrest of spermatogenesis in mammals but are compatible with fertility in female carriers of the same anomaly. In the case of trisomy, mice have extra genomic DNA as well as the chromosomal abnormality, usually present as an extra, unpaired chromosome. Thus, impairment of spermatogenesis in trisomic males could be due to the presence of extra genomic material (i.e. triplicated genes) or due to the chromosomal abnormality and presence of an unpaired chromosome in meiosis. METHODS: In this study, fertility and chromosomal pairing configurations during meiotic prophase were analysed in male mice trisomic for different segments of the genome. Four have an extra segmental or tertiary trisomic chromosome--Ts(17(16))65Dn, Ts(10(16))232Dn, Ts(12(17))4Rk and Ts(4(17))2Lws--and one has the triplicated segment attached to another chromosome--Ts(16C-tel)1Cje. Ts(17(16))65Dn and Ts(16C-tel)1Cje have similar gene content triplication and differ primarily in whether the extra DNA is in an extra chromosome or not. RESULTS: The presence of an intact extra chromosome, rather than trisomy per se, is associated with male sterility. Additionally, sterility is correlated with a high frequency of association of the unpaired chromosome with the XY body, which contains the largely unpaired X and Y chromosomes. CONCLUSIONS: Intact extra chromosomes disrupt spermatogenesis, and unpaired chromosomes establish a unique chromatin territory within meiotic nuclei.     

Interleukin-10 promoter polymorphisms in male and female fertility and fecundity

Interleukin-10 (IL10) is assumed beneficial for a successful pregnancy; it may increase fertility and fecundity. Allele frequencies of IL10 polymorphisms at position -2849, -1082 and -592 were analyzed in association with a past history of fertility and fecundity in men and women of at least 85 years old. Fertility was decreased in association with the -2849 A allele in females; 27% of the AA genotype carriers produced no offspring in marriage compared to 14% of the G allele carriers (odds ratio (OR): 2.2, 95% confidence interval (CI): 1.2-4.2, P=0.01). Effective fecundability was decreased in association with the -2849 A allele in females; 7% of female -2849 AA genotype carriers had a child within 371 days of marriage (therefore, conceived within 3 months of marriage) compared to 28% of female G allele carriers (OR: 0.2, 95% CI: 0.04-0.7, P=0.01). This suggests an association between the -2849 AA genotype and a decreased fertility and fecundity in females.     

Identification of 12 novel mutations in the CFTR gene

Over 200 mutations, besides the deletion