Authors
Dallinga, J.W., Moonen, E.J., Dumoulin, J.C., Evers, J.L., Geraedts, J.P., Kleinjans, J.C.

Title:
Decreased human semen quality and organochlorine compounds in blood.

Journal:
Human Reproduction, 17(8): 1973-1979.2002.

Summary:
There has been immense speculation surrounding the possible decline in male sperm counts over the past 50 years. This debate was amplified with the 1992 publication of a 61 study meta-analysis, suggesting that sperm concentration and volume was decreasing in men. Several thousand man-made chemicals are persistent in the environment and few of these have been tested at either high or background levels during development for their possible endocrine modulating effects. Some researchers have surmised that exposures to chemicals with estrogenic activity during development or childhood may be associated with future reproductive problems. Others have speculated that the anti-androgen or anti-estrogen activity of some chemicals and their metabolites may disturb the delicate hormonal balance required for spermatogenesis.

The objective of this study was to determine if background organochlorine levels play a role in male factor subfertility (MFS) verses a female factor subfertility (FFS) group. In addition, the potential role of genetic factors affecting PCB metabolism were determined in both the FFS and MFS groups. The genes GSTM1 and GSTT1 code for enzymes involved in metabolism. The enzymes involved in the metabolism of xenobiotics are referred to as GST-mu and GST-theta. The polymorphic frequencies of the glutathione S-transferase (GST) GSTMI and GSTTI genes, encoding for these PCB detoxifying enzymes were established in both the FFS and MFS groups of men. There is both geographical and ethnic variation in the occurrence of these genes. Thus, it has been postulated that the absence or presence of these genes may modify the risk of adverse effects due to environmental contaminants.

Couples visiting the Maastricht University Hospital for fertility treatment were divided into two groups. The first included those with extremely poor semen quality, the male factor subfertility (MFS) group (n=31), and the second being those with good or normal semen quality, the female factor subfertility (FFS) group (n=34). Semen samples were examined for several parameters including volume, count and overall progressive motility and morphology. As well, organochlorine compound levels were established in the semen. Similarly, organochlorine compound levels were measured in blood samples and GSTMI and GSTTI genotypes were established using a PCR-based assay. Finally, a questionnaire was given to the participants in order to obtain additional information on demographic and lifestyle factors and occupational exposures.

The analysis showed a strong positive correlation between total PCB concentration and total PCB metabolite concentrations (r2=0.36, p=0.0001) which was not affected by the GSTMI or GSTTI polymorphisms. As well, age was positively correlated with organochlorine blood levels. The seminal organochlorine levels of the 65 volunteers showed a significant relationship between individual and combined PCB metabolite levels and sperm morphology (r2=0.15, p=0.02). Yet, no significant difference was seen between organochlorine levels in blood and semen when comparing the FFS and MFS groups. Within the FFS group increasing levels of combined PCB metabolite concentrations in the blood were significantly correlated with declining sperm count (r2 =0.14, p=0.04) and progressively motile sperm density (PMSC) (r2 =0.17, p=0.02). Such correlations were not found between the unmetabolized component concentrations and sperm parameters. As well, the corresponding correlations were not significant in the MFS group.

Interestingly, this study attempted to look at gene-environment interactions of background organochlorine levels. The results suggested that, in the population studied, organochlorine levels did not contribute to male factor subfertility. As well, the study did not demonstrate an influence of the GSTT1 and GSTM1 polymorphisms on PCB metabolism, however the population studied was very small. The fact that some relationships were found for PCB metabolites and not the unmetabolized components suggests that PCB metabolites are biologically active compounds.