The activity of androgen receptor (AR) is modulated by a polymorphic CAG trinucleotide repeat in the AR gene. In the present study, we investigated hormonal changes among ageing men, and whether the number of AR CAG triplets is related to the appearance of these changes, as well as symptoms and diseases associated with ageing. A total of 213 41-70-year-old men donated blood for hormone analyses (LH, testosterone, oestradiol and SHBG) and answered questions concerning diseases and symptoms associated with ageing and/or androgen deficiency. Of these men, 172 donated blood for the measurement of the CAG repeat length of AR. The CAG repeat region of the AR gene was amplified by polymerase chain reaction (PCR) and the products were sized on polyacrylamide gels. The repeat number was analysed as a dichotomized variable divided according to cut-off limits of the lowest (< or =20 repeats) and the highest quartile (> or =23 repeats), and as a continuous variable. The proportion of men with serum LH in the uppermost quartile (>6.0 IU/L) with normal serum testosterone (>9.8 nmol/L, above the lowest 10%) increased significantly with age (p = 0.01). There were fewer men with this hormonal condition among those with CAG repeat number in the uppermost quartile (> or =23 repeats) (p = 0.03). These men also reported less decreased potency (p < 0.05). The repeat number was positively correlated with depression, as expressed by the wish to be dead (r = 0.45; p < 0.0001), depressed mood (r = 0.23; p = 0.003), anxiety (r = 0.15; p < 0.05), deterioration of general well-being (r = 0.22; p = 0.004), as well as decreased beard growth (r = 0.49; p < 0.0001). A hormonal condition where serum testosterone is normal but LH increased is a frequent finding in male ageing. Only certain types of age-related changes in ageing men were associated with the length of the AR gene CAG repeat, suggesting that this parameter may play a role in setting different thresholds for the array of androgen actions in the male.

Recent studies have shown that aneuploidy in spermatozoa of infertile men with poor semen quality is increased. The purpose of this study was to determine whether poor sperm morphology is associated with the incidence of spermatozoa with numerical chromosome abnormalities. Semen samples from 20 infertile teratozoospermic men were studied using multicolour fluorescence in situ hybridization (FISH). Men were divided into four groups according to the proportion of normal sperm morphology: infertile men with <10% (group A, n=7), 10-19% (group B, n=6), and 20-29% (group C, n=7) of morphologically normal spermatozoa, and controls (group D, n=5) with > or =30% normal forms. Two hybridizations were performed. All the samples were analysed using probes for chromosomes 1 and 7 and, in addition, in group A and in controls with normal semen parameters probes for chromosomes X, Y and 18 were also used. Ten thousand spermatozoa were scored per hybridization. Severely teratozoospermic men (<10% normal forms) had significantly higher frequency of disomy 7, 18, YY, XY and diploidy in their spermatozoa when compared with controls. The results suggest that poor sperm morphology is associated with numerical chromosome abnormalities of spermatozoa. Severely teratozoospermic men may be at an increased risk of producing aneuploid offspring.

Pesticides are some of the most frequently released toxic chemicals into the environment. Exposure to them has been associated with reproductive dysfunction, but the knowledge of the genotoxic risks of these substances is still limited. In vitro and in vivo, many pesticides are shown to induce aneuploidy. Analysis of sperm chromosomes by fluorescence in situ hybridization (FISH) with chromosome-specific probes has obtained increasing popularity in genetic toxicology. Sperm-FISH studies on men exposed to pesticides have yielded conflicting results: in men exposed to multiple pesticides during spraying no increased disomy frequencies in sperm were observed, although one study reported an increased rate of sex chromosome nullisomy. In contrast the two studies conducted in pesticide factories showed increased frequencies of sperm aneuploidy in exposed men compared to controls. The available data indicates that at least some of the commonly used pesticides are capable of inducing aneuploidy in human sperm when the exposure level is high enough.

Fungicides include chemicals that are known aneugens. The purpose of the present study was to investigate whether occupational exposure to these and other agricultural pesticides induces aneuploidy in human sperm. The contribution of lifestyle factors (smoking and alcohol consumption) to the frequency of aneuploid sperm was evaluated as well. The effects of age and sperm concentration were analyzed as confounders. Spermatozoa from 30 healthy farmers were studied before and after exposure to fungicides, using fluorescence in situ hybridization (FISH). Ten thousand spermatozoa were scored per semen sample to determine the disomy and diploidy frequencies for chromosomes 1 and 7. Exposure to fungicides was not associated with sperm aneuploidy. Smoking was significantly associated with sperm carrying an extra chromosome 1 and with diploid sperm as well as with the aggregate frequency of aneuploid sperm. Alcohol consumption, sperm concentration, and age showed inconsistent results before and after the season of exposure to fungicides. For low‐level exposures, such as occupational exposures, the sensitivity of the sperm‐FISH method may not be sufficient. The present study supports earlier ones showing that smoking can increase aneuploidy in human sperm. Environ. Mol. Mutagen. 34:39–46, 1999 © 1999 Wiley‐Liss, Inc.

The incidence of Y-deletions in the study population of infertile Finnish men falls within the range published in other countries.