Biomedical subjects

A J Wyrobek

Publications and source records attributed to A J Wyrobek.

At least 19 recordsLinked to original sources

PubMed2006

The effects of male age on sperm DNA damage in healthy non-smokers.

BACKGROUND: The trend for men to have children at older age raises concerns that advancing age may increase the production of genetically defective sperm, increasing the risks of transmitting germ-line mutations. METHODS: We investigated the associations between male age and sperm DNA damage and the influence of several lifestyle factors in a healthy non-clinical group of 80 non-smokers (mean age: 46.4 years, range: 22-80 years) with no known fertility problems using the sperm Comet analyses. RESULTS: The average percentage of DNA that migrated out of the sperm nucleus under alkaline electrophoresis increased with age (0.18% per year, P = 0.006), but there was no age association for damage measured under neutral conditions (P = 0.7). Men who consumed >3 cups coffee per day had approximately 20% higher percentage tail DNA under neutral but not alkaline conditions compared with men who consumed no caffeine (P = 0.005). CONCLUSIONS: Our findings indicate that (i) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks and (ii) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization, increasing the risks of developmental defects and genetic diseases among offspring.

Adult↗

PubMed2006

Quantitative effects of male age on sperm motion.

BACKGROUND: Semen quality is associated with fertility status, but there is little quantitative information on risk factors that affect semen quality, especially in non-clinical populations. Advancing male age has been associated with a decline in semen quality, with the largest effect being on sperm motility. However, there is little quantitative data on the specific components of sperm motion that are affected by male age. METHODS: We performed linear regression analyses of 14 aspects of semen quality measured by computer-assisted semen analysis (CASA) in a non-clinical cohort of 90 non-smoking men, aged 22-80 years, who had no history of infertility or reproductive problems. RESULTS: We found age-associated declines in CASA-determined motility (% motile, 0.8% per year; % progressively motile, 0.9% per year; % rapidly motile, 0.4% per year, P <or= 0.001) and three quantitative aspects of sperm motion [linearity (LIN), 0.2% per year; straight line velocity (VSL), 0.2% per year, and average path velocity (VAP), 0.3% per year, P < 0.05], with no evidence for age thresholds and no significant association with abstinence duration. Age was not significantly associated with amplitude of lateral head (ALH) displacement, beat cross frequency (BCF) and nuclear elongation or size. CONCLUSIONS: Quantitative analysis of sperm motion indicates that as men age, they produce fewer motile sperm, which are able to travel less along a linear path, thus covering less forward distance per unit time. These findings may have fertility implications for men who choose to delay fatherhood.

Adult↗

PubMed2006

Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm.

This study compares the relative effects of advancing male age on multiple genomic defects in human sperm [DNA fragmentation index (DFI), chromatin integrity, gene mutations, and numerical chromosomal abnormalities], characterizes the relationships among these defects and with semen quality, and estimates the incidence of susceptible individuals for a well characterized nonclinical nonsmoking group of 97 men (22-80 years). Adjusting for confounders, we found major associations between age and the frequencies of sperm with DFI and fibroblast growth factor receptor 3 gene (FGFR3) mutations associated with achondroplasia (P < 0.01) with no evidence for age thresholds. However, we found no associations between age and the frequencies of sperm with immature chromatin, aneuploidies/diploidies, FGFR2 mutations (Apert syndrome), or sex ratio in this cohort. There were also no consistent correlations among genomic and semen-quality endpoints, except between DFI and sperm motility (r = -0.65, P < 0.001). These findings suggest there are multiple spermatogenic targets for genomically defective sperm with substantially variable susceptibilities to age. Our findings predict that as healthy males age, they have decreased pregnancy success with trends beginning in their early reproductive years, increased risk for producing offspring with achondroplasia mutations, and risk of fathering offspring with Apert syndrome that may vary across cohorts, but with no increased risk for fathering aneuploid offspring (Down, Klinefelter, Turner, triple X, and XYY syndromes) or triploid embryos. Our findings also suggest that the burden of genomic damage in sperm cannot be inferred from semen quality, and that a small fraction of men are at increased risk for transmitting multiple genetic and chromosomal defects.

Achondroplasia↗

PubMed2005

Antioxidant intake is associated with semen quality in healthy men.

BACKGROUND: We seek to determine whether dietary and supplement intake of specific micronutrients (zinc and folate) and antioxidants (vitamins C, E and beta-carotene) is associated with semen quality. METHODS: Ninety-seven healthy, non-smoking men provided semen and were interviewed. Average daily nutrient intake from food and supplements was derived from a self-administered food frequency questionnaire. Intake levels were summarized as low, moderate and high. Semen volume, sperm concentration, total sperm count, motility, progressive motility and total progressively motile sperm count (TPMS) were measured. RESULTS: After controlling for covariates, a high intake of antioxidants was associated with better semen quality but, in almost all cases, there was no clear dose relationship in that moderate intake groups had the poorest semen quality. For example, positive associations were observed between vitamin C intake and sperm number as reflected in the higher mean count (P=0.04), concentration (P=0.05) and TPMS (P = 0.09); between vitamin E intake and progressive motility (P = 0.04) and TPMS (P = 0.05); and between beta-carotene intake and sperm concentration (P = 0.06) and progressive motility (P = 0.06). Folate and zinc intake were not associated with improved semen quality. CONCLUSIONS: In a convenience sample of healthy non-smoking men from a non-clinical setting, higher antioxidant intake was associated with higher sperm numbers and motility.

Adult↗

PubMed2004

Detection of structural and numerical chromosomal abnormalities by ACM-FISH analysis in sperm of oligozoospermic infertility patients.

BACKGROUND: Modern reproductive technologies are enabling the treatment of infertile men with severe disturbances of spermatogenesis. The possibility of elevated frequencies of genetically and chromosomally defective sperm has become an issue of concern with the increased usage of ICSI, which can enable men with severely impaired sperm production to father children. Several papers have been published reporting aneuploidy in oligozoospermic patients, but relatively little is known about chromosome structural aberrations in the sperm of these patients. METHODS: We examined sperm from infertile, oligozoospermic individuals for structural and numerical chromosomal abnormalities using a multicolour ACM fluorescence in situ hybridization (FISH) assay that utilizes DNA probes specific for three regions of chromosome 1 to detect human sperm that carry numerical chromosomal abnormalities plus two categories of structural aberrations: duplications and deletions of 1pter and 1cen, and chromosomal breaks within the 1cen-1q12 region. RESULTS: There was a significant increase in the average frequencies of sperm with duplications and deletions in the infertility patients compared with the healthy concurrent controls. There was also a significantly elevated level of breaks within the 1cen-1q12 region. There was no evidence for an increase in chromosome 1 disomy, or in diploidy. CONCLUSIONS: Our data reveal that oligozoospermia is associated with chromosomal structural abnormalities, suggesting that oligozoospermic men carry a higher burden of transmissible, chromosome damage. The findings raise the possibility of elevated levels of transmissible chromosomal defects following ICSI treatment.

Adult↗

PubMed2003

Gene expression changes in mouse brain after exposure to low-dose ionizing radiation.

PURPOSE: To characterize the cellular functions associated with the altered transcript profiles of mouse brain exposed to low-dose in vivo gamma-irradiation. MATERIALS AND METHODS: Cerebral RNA was isolated at 30 min and 4 h after whole-body irradiation at 0.1 or 2 Gy, hybridized to random oligonucleotide arrays, and evaluated for time and dose-response patterns by multifactorial analyses. RESULTS: Brain irradiation modulated the expression patterns of 1574 genes, of which 855 showed more than 1.5-fold variation. about 30% of genes showed dose-dependent variations, including genes exclusively affected by 0.1 Gy. About 60% of genes showed time-dependent variation with more genes affected at 30 min than at 4 h. Early changes involved signal transduction, ion regulation and synaptic signalling. Later changes involved metabolic functions including myelin and protein synthesis. Low-dose radiation also modulated the expression of genes involved in stress response, cell-cycle control and DNA synthesis/repair. CONCLUSIONS: Doses of 0.1 Gy induced changes in gene expression that were qualitatively different from those at 2 Gy. The findings suggest that low-dose irradiation of the brain induces the expression of genes involved in protective and reparative functions, while down-modulating genes involved in neural signalling activity.

Animals↗

PubMed2003

The association of age and semen quality in healthy men.

BACKGROUND: Although the effect of maternal age on fertility is well known, it is unclear whether paternal age also affects fertility. This cross-sectional study sought to characterize the association between age and semen quality, a well-known proxy of fertility status. METHODS: A convenience sample of 97 non-smoking men (aged 22-80 years) without known fertility problems was recruited from a national government laboratory. The men provided semen samples and information relating to lifestyle, diet, medical and occupational details. Semen volume (ml), sperm concentration (x10(6)/ml), total sperm count (x10(6)), motility (%), progressive motility (%) and total progressively motile sperm count (x10(6)) were measured. RESULTS: After adjusting for covariates, semen volume decreased by 0.03 ml per year of age (95% CI: -0.05, -0.01); motility decreased by 0.7% per year (95% CI: -0.92, -0.43); progressive motility decreased by 3.1% per year (95% CI: -4.5, -1.6); and total progressively motile sperm count decreased by 4.7% per year (95% CI: -7.2, -2.2). There was a suggested decrease in sperm concentration and count. The proportion of men with abnormal volume, concentration and motility was significantly increased across the age decades. CONCLUSIONS: In a convenience sample of healthy men from a non-clinical setting, semen volume and sperm motility decreased continuously between 22-80 years of age, with no evidence of a threshold.

Adult↗

PubMed2002

Sperm aneuploidy in fathers of children with paternally and maternally inherited Klinefelter syndrome.

BACKGROUND: It is unclear whether frequency of sperm aneuploidy is associated with risk of fathering children with trisomy. METHODS: We recruited 36 families with a boy with Klinefelter syndrome (KS), interviewed the fathers about their exposures and medical history, received a semen sample from each father, and collected blood samples from the mother, father and child. We applied a multicolour fluorescent in-situ hybridization assay to compare the frequencies of sperm carrying XY aneuploidy and disomies X, Y and 21 in fathers of maternally and paternally inherited KS cases. RESULTS: Inheritance of the extra X chromosome was paternal in 10 and maternal in 26 families. Fathers of paternal KS cases produced higher frequencies of XY sperm (P = 0.02) than fathers of maternal KS cases. After controlling for age, the major confounding variable, the difference between the two groups was no longer significant (P less-than-or-equal 0.2). Also, there were no significant differences between the parental origin groups for disomy X, Y or 21. CONCLUSIONS: Men who fathered a child with a Klinefelter syndrome produced higher frequencies of XY sperm aneuploidy, which is explained, in part, by both paternal age and parent of origin.

Adult↗

PubMed2001

Frequency of XY sperm increases with age in fathers of boys with Klinefelter syndrome.

With increasing availability of drugs for impotence and advanced reproductive technologies for the treatment of subfertility, more men are fathering children at advanced ages. We conducted a study of the chromosomal content of sperm of healthy men aged 24-57 years to (a) determine whether father's age was associated with increasing frequencies of aneuploid sperm including XY, disomy X, disomy Y, disomy 21, and sperm diploidy, and (b) examine the association between the frequencies of disomy 21 and sex-chromosomal aneuploidies. The study group consisted of 38 fathers of boys with Klinefelter syndrome (47, XXY) recruited nationwide, and sperm aneuploidy was assessed using multicolor X-Y-21 sperm FISH ( approximately 10,000 sperm per donor). Paternal age was significantly correlated with the sex ratio of sperm (Y/X; P=.006) and with the frequency of XY sperm (P=.02), with a clear trend with age by decades (P<.006). Compared with fathers in their 20s (who had an average frequency of 7.5 XY sperm per 10,000), the frequencies of XY sperm were 10% higher among fathers in their 30s, 31% higher among those in their 40s, and 160% higher among those in their 50s (95% CI 69%-300%). However, there was no evidence for age effects on frequencies of sperm carrying nullisomy sex; disomies X, Y, or 21; or meiosis I or II diploidies. The frequencies of disomy 21 sperm were significantly associated with sex-chromosomal aneuploidy (P=.04)-in particular, with disomy X (P=.004), but disomy 21 sperm did not preferentially carry either sex chromosome. These findings suggest that older fathers produce higher frequencies of XY sperm, which may place them at higher risk of fathering boys with Klinefelter syndrome, and that age effects on sperm aneuploidy are chromosome specific.

Adult↗

PubMed2001

Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse.

Etoposide, a topoisomerase II inhibitor widely used in cancer therapy, is suspected of inducing secondary tumors and affecting the genetic constitution of germ cells. A better understanding of the potential heritable risk of etoposide is needed to provide sound genetic counseling to cancer patients treated with this drug in their reproductive years. We used a mouse model to investigate the effects of clinical doses of etoposide on the induction of chromosomal abnormalities in spermatocytes and their transmission to zygotes by using a combination of chromosome painting and 4',6-diamidino-2-phenylindole staining. High frequencies of chromosomal aberrations were detected in spermatocytes within 64 h after treatment when over 30% of the metaphases analyzed had structural aberrations (P < 0.01). Significant increases in the percentages of zygotic metaphases with structural aberrations were found only for matings that sampled treated pachytene (28-fold, P < 0.0001) and preleptotene spermatocytes (13-fold, P < 0.001). Etoposide induced mostly acentric fragments and deletions, types of aberrations expected to result in embryonic lethality, because they represent loss of genetic material. Chromosomal exchanges were rare. Etoposide treatment of pachytene cells induced aneuploidy in both spermatocytes (18-fold, P < 0.01) and zygotes (8-fold, P < 0.05). We know of no other report of an agent for which paternal exposure leads to an increased incidence of aneuploidy in the offspring. Thus, we found that therapeutic doses of etoposide affect primarily meiotic germ cells, producing unstable structural aberrations and aneuploidy, effects that are transmitted to the progeny. This finding suggests that individuals who undergo chemotherapy with etoposide may be at a higher risk for abnormal reproductive outcomes especially within the 2 months after chemotherapy.

Aneuploidy↗

PubMed2001

Effects of male age on semen quality and fertility: a review of the literature.

OBJECTIVE: To review the literature on the association between male age and semen quality (semen volume, concentration, motility, and morphology) and fertility status (pregnancy rate and time to pregnancy/subfecundity). METHOD(S): Review of English language-published research over the last 20 years from January 1, 1980, through December 31, 1999, using MEDLINE and Biosis databases. Studies with insufficient numbers of subjects, case reports, case series, or anecdotal data were excluded. RESULT(S): Among the methodologically stronger studies, decreases in semen volume of 3%-22%, decreases in sperm motility of 3%-37%, and decreases in percent normal sperm of 4%-18% were likely when comparing 30-year-old men to 50-year-old men. Most studies examining fertility status suggest a relationship between male age and fertility, but the results are most likely confounded by female partner age. Among studies that did control for female age, comparisons between men under 30 and men over 50 found relative decreases in pregnancy rates between 23% and 38%. A comparison of the various age categories showed that the increased risks for subfecundity ranged from 11% to 250%. CONCLUSION(S): The weight of the evidence suggests that increased male age is associated with a decline in semen volume, sperm motility, and sperm morphology but not with sperm concentration.

Adult↗

PubMed2001

Evaluation of inter-scorer and inter-laboratory reliability of the mouse epididymal sperm aneuploidy (m-ESA) assay.

The mouse epididymal sperm aneuploidy (mESA) assay using 3-chromosome fluorescence in situ hybridization (FISH) was recently developed for assessing the aneugenic potential of chemicals on male germ cells. This study was designed to identify the major technical factors that affect inter-scorer and inter-laboratory variability of the mESA assay. Two laboratories participated in this study (GSF and Lawrence Livermore National Laboratory, LLNL). Mice (102/ElxC3H/El) F(1) were exposed in one laboratory (GSF) to vinblastine (VBL; single intraperitoneal injection of 0, 0.5, 1.0 or 2.0 mg/kg), one of the 10 priority compounds of the Commission of the European Communities (CEC) Aneuploidy Program. Twenty-two days later the mESA assay was applied to analyze sperm aneuploidy. In the initial evaluation, small but statistically significant differences were found between the two laboratories in baseline frequencies and there was also disagreement in the determination of a VBL aneuploid effect. Therefore, experiments were conducted to identify the sources of the inter-laboratory differences and technical factors that affected assay reliability and the VBL study was repeated. A harmonization experiment was conducted by bringing the microscope scorers from both laboratories to the same site (LLNL) for a cross-training exercise. Following this exercise, a second group of VBL-treated and control mice were evaluated, and we concluded that VBL is not a sperm aneugen. Our research has identified scoring criteria as the major source of inter-laboratory variation and emphasizes the importance of strict technical controls for the mESA assay, including controlling slide preparations for treatment-induced reductions in sperm count, coding of slides and selection of statistical tests. These considerations are particularly important for the interpretation of small effects (< or =2-fold) on sperm aneuploidy. Our findings suggest that 2-fold differences in frequencies can result from differences among scorers, samples and treatment groups, and are readily within the normal variation for the mESA assay. Such small differences should be viewed with caution until independently confirmed.

Aneuploidy↗

PubMed2000

Multicolor FISH analysis of chromosomal breaks, duplications, deletions, and numerical abnormalities in the sperm of healthy men.

Transmitted de novo structural chromosomal abnormalities, the majority of which are paternally derived, can lead to abnormal reproductive outcomes as well as genetic diseases in offspring. We developed and validated a new multicolor FISH procedure (sperm ACM, which utilizes DNA probes specific for the alpha [1cen], classical, [1q12], and midi [1p36.3] satellites of chromosome 1) which utilizes DNA probes specific for three regions of chromosome 1 to detect human sperm that carry numerical abnormalities plus two categories of structural aberrations: (1) duplications and deletions of 1pter and 1cen, and (2) chromosomal breaks within the 1cen-1q12 region. In healthy men, the average frequencies of sperm with duplications and deletions were (a) 4.5 +/- 0.5 and 4.1 +/- 1.3 per 10(4) involving 1pter and (b) 0.9 +/- 0.4 and 0.8 +/- 0.3 per 10(4) involving 1cen, respectively. The frequency of sperm exhibiting breaks within the 1cen-1q12 region was 14.1 +/- 1.2 per 10(4). Structural aberrations accounted for 71% of the abnormalities detected by sperm ACM, which was significantly higher than numerical abnormalities (P=2x10-8). Our findings also suggest that, for healthy men, (a) sperm carrying postmeiotic chromosomal breaks appear to be more prevalent than those carrying products of premeiotic or meiotic breakage or rearrangements, (b) the high frequency of chromosome breaks measured after "fertilization" by the hamster-egg cytogenetic method already appear to be present and detectable within human sperm by FISH, and (c) there are nonrandom and donor-specific distributions of breakpoint locations within 1q12 in sperm. FISH facilitates the analysis of much larger numbers of sperm than was possible when the hamster-egg method was used. Therefore, FISH-based procedures for simultaneously detecting chromosomal breaks, rearrangements, and numerical abnormalities in sperm may have widespread applications in human genetics, genetic toxicology, and reproductive medicine.

Animals↗

PubMed1999

Numerical and structural chromosomal abnormalities detected in human sperm with a combination of multicolor FISH assays.

A pair of multicolor FISH assays (X-Y-21 and A-M-16) was developed for human sperm to simultaneously measure sex ratios; aneuploidies involving chromosomes 1, 16, 21, X, and Y; meiotic diploidies; and structural aberrations involving chromosome 1p. Sex ratios in sperm were not significantly different from unity among healthy men. Baseline frequencies of disomic sperm for chromosomes 1, 8, and 21 were similar (6.7 per 10(4) sperm, 95% CI of 5.6-8.1), suggesting that among these three chromosomes, chromosome 21 was not especially prone to nondisjunction. Frequencies of disomy 16 sperm were significantly lower, however (3.5 per 10(4) sperm, 95% CI of 2.0-6.2; P < 0.02). The baseline frequencies of sperm disomy by FISH for chromosomes 16 and 21 were validated against aneuploidy data obtained by the hamster-egg technique for human sperm cytogenetics. The frequencies of X-X, Y-Y, X-Y ("Klinefelter") sperm and sex-null ("Turner") sperm were 5.5, 5.1, 5.5, and 7.8 per 10(4) sperm, respectively. For chromosomes 16 and 21, the frequencies of nullisomic and disomic sperm were similar, suggesting that gain and loss events occurred symmetrically. However, more gain than loss was reported for chromosomes 1, X, and Y. The frequency of MI and MII diploid sperm (with flagella) was approximately 12 per 10(4) (range 8.3-16.7 per 10(4) sperm). Based on flagella data, the frequency of somatic cells in the semen was estimated to be approximately 1.8 per 10(4) sperm. Loss or gain of a portion of chromosome-arm 1p occurred in 5.5 per 10(4) sperm, and the percentage of sperm carrying structural aberrations within the haploid genome as calculated from FISH (1.4%), was similar to that obtained with the hamster-egg technique. These complementary sperm FISH assays have promising applications in studies of chromosomally abnormal sperm after exposure to occupational, medical, and environmental toxicants.

Adult↗

PubMed1999

Absence of selection against aneuploid mouse sperm at fertilization.

Is there selection against aneuploid sperm during spermatogenesis and fertilization? To address this question, we used male mice doubly heterozygous for the Robertsonian (Rb) translocations Rb(6. 16)24Lub and Rb(16.17)7Bnr, which produce high levels of sperm aneuploid for chromosome 16, the mouse counterpart of human chromosome 21. The frequencies of aneuploid male gametes before and after fertilization were compared by analyzing approximately 500 meiosis II spermatocytes and approximately 500 first-cleavage zygotes using fluorescence in situ hybridization with a DNA painting probe mixture containing three biotin-labeled probes specific for chromosomes 8, 16, and 17 plus a digoxigenin-labeled probe specific for chromosome Y. Hyperhaploidy for chromosome 16 occurred in 20.0% of spermatocytes and in 21.8% of zygotes. Hypohaploidy for chromosome 16 occurred in 17.0% and 16.7% of spermatocytes and zygotes, respectively. In addition, there was no preferential association between chromosome 16 aneuploidy and either of the sex chromosomes, nor was there an elevation in aneuploidy for chromosomes not involved in the Rb translocations. These findings provide direct evidence that there is no selection against aneuploid sperm during spermiogenesis, fertilization, and the first cell cycle of zygotic development.

Aneuploidy↗

PubMed1998

Advances in the automated detection of metaphase chromosomes labeled with fluorescence dyes.

Applications of fluorescence in situ hybridization (FISH) for translocation studies and biological dosimetry would benefit substantially from reliable and efficient automatic detection of metaphase chromosomes labeled with fluorescent dyes. We replicated and evaluated a fluorescence metaphase finder previously developed at the Medical Research Council (MRC), Human Genetics Unit (Scotland) and at Lawrence Berkeley Laboratory (LBL; California). The MRC/LBL system seemed to detect nearly all of the metaphases on the test slides, but it presented an unacceptable number of false positives (about five false positives per one true positive). Furthermore, we determined that the system actually overcalled true detections by counting certain metaphase spreads twice (duplicates). Through modifications of the MRC/LBL system, we developed the Lawrence Livermore National Laboratory (LLNL) system, which minimizes the detection of duplicates, incorporates new detection features, uses a binary decision tree (BDT) for classification, and provides functionalities to improve scanning accuracy and improve the post-detection review. To test the new system, DAPI-stained preparations of metaphase chromosomes from blood lymphocytes of four unrelated donors were placed on slides in drops ranging from 7 mm to 20 mm in diameter. Drops contained between 5 and 200 scorable metaphases each. The LLNL system achieved approximately 90% detection of non-duplicated metaphases as verified by an expert cytogeneticist, with typically less than one false positive per every one true positive detected.

Automation↗

PubMed1998

Micronuclei and developmental abnormalities in 4-day mouse embryos after paternal treatment with acrylamide.

The developmental consequences of paternal exposure to acrylamide (50 mg/kg i.p. for 5 days) were assessed in preimplantation embryos. There was a significant increase in the proportion of morphologically abnormal embryos after postmeiotic treatment during spermatogenesis (88.7% vs. 14.8% in control). Abnormal embryos had an average of 1.8 +/- 3.5 cells and > 80% had at least one fragmented nucleus. In addition, morphologically normal embryos were significantly delayed (34.3 +/- 12.8 cells per embryo vs. 57.6 +/- 15.7 in control, P < 0.001). Acrylamide caused 10- and 20-fold increases in frequencies of cells with micronuclei (MN) in morphologically normal and abnormal embryos, respectively (41 and 93 MN per 1,000 cells). Both centromere-negative (MN-) and centromere-positive (MN+) were induced. Nuclei of abnormal embryos were significantly larger (900 microm2 vs. 250 microm2) than controls. In addition, MN of abnormal embryos were larger than those of normal embryos (21.2 microm2 vs. 6.5 microm2, P < 0.01). Among control embryos, MN+ were significantly larger than MN- (P < 0.05). These findings suggest that the preimplantation embryo is a sensitive indicator of paternally transmitted effects on early development. Multiple mechanisms appear to be involved, including cytogenetic damage, proliferation arrest/delay, and fertilization failure. Future studies are needed to establish how induced cytological defects in preimplantation embryos contribute to birth defects and other postimplantation abnormalities.

Abnormalities, Drug-Induced↗

PubMed1998

Smoking cigarettes is associated with increased sperm disomy in teenage men.

OBJECTIVE: To determine whether moderate cigarette smoking and alcohol consumption in teenage men is associated with increases in disomic sperm and detectable changes in semen quality. DESIGN: Cohort study. SETTING: Military recruiting station, Teplice, Czech Republic. PATIENT(S): Ten current smokers (20 cigarettes per day for at least 2 years, exposure confirmed by urine cotinine) who also consumed alcohol and 15 nonsmokers. All patients were exactly 18 years old, healthy, and of unproven fertility. MAIN OUTCOME MEASURE(S): Sperm aneuploidy by multicolor fluorescence in situ hybridization for chromosomes 8, X, and Y; conventional semen analyses; computer-aided sperm analysis for motility; and sperm chromatin structure analysis. RESULTS: Smokers showed elevated frequencies of sperm aneuploidy (Y disomy, P <0.001; aggregate of X, Y, and 8 disomies, P <0.01); reduced linearity of sperm motion (P <0.05); and more "round-headed" sperm (P <0.01). Smokers' semen contained fewer sperm (P <0.001) and fewer motile sperm (P <0.02), which was attributable, in part, to shorter abstinence intervals among smokers (P <0.02). CONCLUSION(S): Cigarette smoking among teenagers was associated with increases in disomic sperm and a diminution in specific aspects of semen quality. Such defects may affect male fertility and may increase future chances of fathering offspring with aneuploidy syndromes.

Adolescent↗