Sperm pathology: a step beyond descriptive morphology. Origin, characterization and fertility potential of abnormal sperm phenotypes in infertile men

Sperm pathology is presented as the discipline of characterizing structural and functional deficiencies in abnormal spermatozoa. This concept complements that of sperm morphology mainly concerned with the appearance of spermatozoa. These two notions collaborate in providing correlations of prognostic value with sperm fertilizing capacity, explaining the mechanisms of sperm inefficiency, suggesting strategies to improve fertilization and opening a door to molecular genetic studies. Phenotypes of genetic origin involving sperm heads, flagella and the neck region are presented describing their clinical manifestations, sperm structure, cytochemistry and genetic background. When available, animal models are used to highlight possible genetic mechanisms. Sperm pathologies secondary to andrological conditions or environmental factors are described, stressing the non-specific nature of the sperm response to noxious agents. The available literature on the prognostic value of sperm pathologies in ICSI is also reviewed. Flagellar anomalies bear a good prognosis, but those affecting the acrosome, sperm chromatin and the neck region entail an increasing chance of failure, which highlights the differential roles played by specific sperm components in fertilization, implantation and early embryonic development. A final discussion is devoted to genetic counselling and the risks involved in using immotile or abnormal spermatozoa in assisted reproduction.     

阿昌族与汉族维生素D受体基因Fok多态性

目的　了解维生素 D受体基因多态性在中国不同民族中的分布。方法　应用聚合酶链反应 -限制性片段长度多态性分析、基因测序等技术检测 6 8名阿昌族人和 92名汉族人的维生素 D受体基因Fok 多态性 ,比较两组维生素 D受体基因型和等位基因的分布频率。结果　在 6 8名阿昌族人中 FF基因型占 18%、Ff基因型占 35 %、ff基因型占 4 7% ,而在 92名汉族人中 FF基因型占 2 2 %、Ff基因型占 5 2 %、ff基因型占 2 6 %。两组维生素 D受体基因型的分布频率差异有显著性 (χ2 =7.716 ,P=0 .0 2 1)。结论　阿昌族与汉族维生素 D受体基因 Fok 多态性分布频率差异有显著性。     

Sequence Analysis of the RNA Polymerase Gene of Foot-and-Mouth Disease Virus Serotype Asia1

The complete nucleotide (nt.) sequence of the RNA polymerase (3D) gene and 81 nt. in the 3-untranslated region of foot-and-mouth disease virus (FMDV) serotype Asia1 (IND63/72) was determined and compared with the sequence of other FMDV serotypes. The 3D genomic region was 1410 nt. long encoding 470 amino acids with an inframe stop codon (TAA) at nt. position 1411–1413. The deduced amino acid sequence of the protein showed 8 conserved motifs as reported in other picornaviruses, 2 of which are 100% identical across the serotypes. Antigenic regions in the polymerase protein were predicted and found to be located at the N-terminus of the protein. The phylogenetic analysis showed that the FMD viruses were segregated into different clusters based on geographical origin; the Asia1 virus did not cluster tightly with any of the geographical groups.     

What should we do with donated embryos that may be genetically affected?

The ethical and legal issues arising from genetic screening in embryo donation are discussed in relation to two recent cases where embryos with uncertain genetic health were offered for donation.     

Predictive genetic testing in children and adults: a study of emotional impact

AIM—To determine whether, following predictive genetic testing for familial adenomatous polyposis (FAP), children or adults receiving positive results experience clinically significant levels of anxiety or depression, and whether children receiving positive results experience higher levels of anxiety or depression than adults receiving positive results.
DESIGN—Two studies, one cross sectional and one prospective.
SAMPLE—208 unaffected subjects (148 adults and 60 children) at risk for FAP who have undergone genetic testing since 1990.
MAIN MEASURES—Dependent variables: anxiety, depression; independent variables: test results, demographic measures, psychological resources (optimism, self-esteem).
RESULTS—Study 1. In children receiving positive results, mean scores for anxiety and depression were within the normal range. There was a trend for children receiving positive results to be more anxious and depressed than those receiving negative results. In adults, mean scores for anxiety were within the normal range for those receiving negative results, but were in the clinical range for those receiving positive results, with 43% (95% CI 23-65) of the latter having scores in this range. Regardless of test result, adults were more likely to be clinically anxious if they were low in optimism or self-esteem. Children receiving positive or negative results did not experience greater anxiety or depression than adults. Study 2. For children receiving a positive test result, mean scores for anxiety, depression, and self-esteem were unchanged over the year following the result, while mean anxiety scores decreased and self-esteem increased after receipt of a negative test result over the same period of time.
CONCLUSION—Children, as a group, did not show clinically significant distress over the first year following predictive genetic testing. Adults were more likely to be clinically anxious if they received a positive result or were low in optimism or self-esteem, with interacting effects. The association between anxiety, self-esteem, and optimism suggests that counselling should be targeted, not only at those with positive test results, but also at those low in psychological resources.


Keywords: genetic testing; children; familial adenomatous polyposis; emotional impact     

Genetic susceptibility to age related macular degeneration

Age related macular degeneration (AMD) is the leading cause of visual impairment in the elderly and a major cause of blindness in the developed world. The disease can take two forms, geographic atrophy and choroidal neovascularisation. The pathogenesis of AMD is poorly understood. There are undoubtedly environmental and other risk factors involved and the adverse effect of smoking is well established. Several studies have shown that genetic factors are important but leave uncertainty about the magnitude and nature of the genetic component and whether it varies with the type of AMD. Several hereditary retinal dystrophies show similarities to AMD and these genes are potential candidate susceptibility genes. Particular interest has focused on the ABCR gene which is responsible for autosomal recessive Stargardt macular dystrophy. It has been claimed that heterozygotes for ABCR mutations are predisposed to AMD but the data are conflicting. Studies of the genes responsible for autosomal dominant Sorsby fundus dystrophy, Doyne honeycomb retinal dystrophy, and Best disease have given negative results. In one large AMD family, linkage has been reported to markers in 1q25-q31. Recent data suggest that the ApoE epsilon4 allele may be associated with reduced risk of AMD. A better understanding of the genetic factors in AMD would contribute to understanding the pathogenesis. If those at risk could be identified it may be possible to modify lifestyle or develop novel therapies in the presymptomatic stage to prevent disease or decrease its severity.     

Interest in genetic testing among first-degree relatives of breast cancer patients

The recent cloning of a breast-ovarian cancer susceptibility gene (BRCA1), and determination of the locus of a related gene (BRCA2), offers potential for clinical genetic testing for breast cancer susceptibility. This study examined interest in and expectations about an impending genetic test among first-degree relatives (FDRs) of breast cancer patients. One hundred five females completed two structured telephone interviews to assess demographics, breast cancer risk factors, psychological factors, and attitudes about genetic testing for breast cancer susceptibility. Overall, 91% of FDRs said that they would want to be tested, 4% said they would not, and 5% were uncertain. The most commonly cited reasons for wanting genetic testing were to learn about one's children's risk, to increase use of cancer screening tests, and to take better care of oneself. Women with less formal education were motivated by childbearing decisions and future planning to a greater degree than were women with education beyond high school. Most women anticipated a negative psychological impact of positive test results, involving increased anxiety (83%), depression (80%), and impaired quality of life (46%). In addition, 72% of women indicated that they would still worry if they tested negative. In multivariate regression analysis, level of baseline depression was the strongest predictor of an anticipated negative impact of genetic testing (Beta =.15; P,.0001). These results suggest that the demand for genetic testing for breast cancer susceptibility may be great, even among women who are not likely to have predisposing mutations. Prior to widespread availability of such testing, it will be critical to develop informed consent protocols to educate individuals about the benefits and limitations of predictive testing for this multifactorial disease. © 1995 Wiley-Liss, Inc.     

Occurrence of neural tube defects among first-, second-, and third-degree relatives of probands: Results of a United States study

Data on the occurrence of neural tube defects in first-, second-, and third-degree relatives of probands were collected in a United States study. The proportions of affected individuals were 3.2%, 0.5%, and 0.17% respectively. These findings are compared to those from other recent North American studies, and differences are discussed. It is pointed out that accurate recurrence risk figures may not be available, and that caution should be used when counseling families with relatives who are affected with NTD.     

Sources of behavioral deviation modeled by early color preferences in quail. III. Developmental stability and normative canalization

Successful artificial selection of quail (C. coturnix japonica) for divergent early approach preferences for, and imprintabilities to, the wavelength characteristics of otherwise identical visual stimuli decreased the trait's developmental stability. The developmental error that resulted from selecting for extreme initial preferences was associated with enhanced imprintabilities. Conversely, the developmental error that resulted from selecting for extreme imprintabilities was associated with enhanced expression of directional gene effects in extreme initial preferences. The data are attributed to selectively relaxed normative canalization of trait development, and to related enhanced expression of genetic, environmental, and stochastic influences in trait deviations.