Authors:
Hauser R, Chen Z, Pothier L, Ryan L, Altshul L.

Title:
The relationship between human semen parameters and environmental exposure to polychlorinated biphenyls and p,p'-DDE.

Source:
Environmental Health Perspectives. Online 19 May 2003

Summary:
The issue of declining semen quality over the past few decades has been widely debated among researchers. Some studies confirm that semen quality has decreased, while others report no change or improvements in semen quality. One such study by Younglai et al (1998) reported decreasing sperm counts in men sampled from Canadian fertility clinics over the period 1984-1996, with significant variation between clinics, suggesting regional differences. Most studies support this finding that there are geographic variations in semen quality which may be due to several factors including lifestyle factors and environmental exposures. Associations between environmental exposure to persistent lipophilic chemicals such as polychlorinated biphenyls (PCBs) and derivatives of DDT (p,p'-DDE) and decreased semen quality would be important findings due to the widespread distribution of these chemicals in the general population. Linking temporal changes in semen quality over time may be complicated by apparent trends which suggest that levels of organochlorines including p,p'-DDE and PCBs are declining in the environment due in part to restrictions and regulations for their use. Similarly, organochlorine levels have declined in adipose tissues in fish, animals and humans over the past 25 years. How trends in environmental and biological levels of these chemicals in response to further regulations and restrictions will impact studies on human health endpoints remains to be seen.

This study was conducted to determine the association of serum PCB and p,p'-DDE levels and semen quality in a group of men referred to a Massachusetts andrology lab for semen analysis. The study period was January 2000-October 2001 and included men with varying fertility. Men receiving hormonal treatments for infertility, or post-vasectomy cases were excluded from the analysis. Lifestyle and medical history data were obtained by questionnaire. Semen samples were produced by masturbation following a recommended 48 h period of abstinence (actual abstinence times were recorded by questionnaire). Semen parameters (sperm concentration, motility) were determined used computer-aided semen analysis (CASA) using Makler sperm counting chambers. Morphology was determined in accordance with World Health Organization (WHO) methodology (1999) and scored as normal or abnormal using strict criteria by Kruger et al (1998). Blood samples were collected on the same day as the semen sample and analyzed for the presence of 57 individual PCB congeners and p,p'-DDE, with serum lipid correction.

The study population consisted of 212 men; 40 with a sperm concentration less than 20 million/ml, 97 with less than 50% motility and 58 men with less than 4% normally shaped sperm (below reference values suggests subfertility). The subjects were primarily Caucasian (79%) with 6% African-American and 8% Hispanic with a mean age was 36 years. Most subjects had never smoked (73%). Advanced age and Hispanic ethnic origin were associated with subfertility. As so few men were smokers it was difficult to investigate the relationship between smoking and semen quality in this study.

PCB and p,p'-DDE levels were widely distributed among the subjects, with serum levels of p,p'-DDE much higher than levels of individual PCB congeners.

Using a multivariate analysis which included age, smoking status and abstinence times, there were significant dose response relationships between PCB 138 (potential estrogenic activity) and decreased motility and morphology but no relationship with sperm concentration. Dose-response relationships were also observed between cytochrome p450 enzyme inducer class PCBs and decreased sperm motility and morphology. Both estrogenic and anti-estrogenic, dioxin-like PCBs also exhibited weak associations with decreased motility and morphology.

This study examined PCB levels on the basis of individual congeners and on the basis of structure-activity groupings; Group 1 cytochome p450 enzyme inducers, Group 2 potential estrogenic activity and Group 3 potential anti-estrogenic, dioxin-like activity. The wide range of individual PCB congeners, each with individual biological and structural properties, makes it difficult to assess groups of PCBs for their impact on health endpoints. One of the strengths of this paper is the grouping of PCB congeners on the basis of structure-activity. There are still limitations to this approach; sum of PCBs, even grouped by structure-activity, do not account for differential activities using a weighting factor. Groupings are based on general potential biological activity, not on potential testicular toxicity in humans or animals.

It is biologically plausible that both PCBs and p,p'-DDE may affect sperm quality, as shown by their ability to traverse the blood-testis barrier and supporting animal studies. Previous studies have demonstrated an association between semen PCB levels and decreased semen quality. Studies conducted in the Netherlands have shown that serum/semen PCB metabolites were associated with decreased motile sperm concentration while a study of Swedish men demonstrated an association between PCB 153 and sperm motility and serum testosterone:sex hormone binding globulin ratio.

One of the weaknesses of the present study, shared by many other studies, is the use of subjects undergoing investigations for infertility treatments. This 'special population' is not representative of the general population and as such, the generalization of these results to the general population may be limited. However, the authors suggest that unless this special population differs in response to chemical exposure compared to the general population, the generalization may not necessarily be limited. One must consider, however, that male infertility may have a genetic component which may also render individuals more susceptible to gene-environment interactions. This is an area that remains to be investigated further.

This study provides further information regarding the association between environmental exposures and semen quality. Generalization of these results to the general population should be made with care given the modest sample size and specialized subject pool in this study. Due to the widespread distribution of PCBs in individuals, further investigations examining accumulated environmental chemicals and human health parameters, including semen quality, are essential.