Fertility and markers of male reproductive function in Inuit and European populations spanning large contrasts in blood levels of persistent organochlorines

Abstract

Objective: We synthesized the main findings from an international epidemiologic study on the impact of biopersistent organic pollutants (POPs) on human reproductive function.

Data sources and extraction: We used a database with interview and biological data from 2,269 women and their spouses, and 18 published core papers.

Data synthesis: The study did not provide direct evidence of hormone-like activity of the polychlorinated biphenyl (PCB) congener CB-153 and the main dichlorodiphenyltrichloroethane (DDT) metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), as serum concentrations of these compounds were not consistently related to either endogenous or exogenous hormone activity in serum. Nevertheless several links bewteen POP exposure and biomarkers of male reproductive function were identified. First, an association between high CB-153 serum levels and low sperm counts was detected within a subgroup of men with short androgen receptor CAG repeat length. Second, a relationship between increased CB-153 serum concentrations and decreased sperm motility was seen in all four studied regions, and indications of reduced neutral alpha-glucosidase activity in seminal plasma point to a post-testicular effect. Third, damage of sperm chromatin integrity was considerably less frequent in Greenlandic Inuits compared with that in European groups, and only in the latter was impairment of sperm chromatin integrity related to POPs. Despite these effects, fertility in terms of time taken to conceive was not related to POPs except in Inuits. A likely explanation of the latter was not identified.

Conclusions: POPs may interfere with male reproductive function without major impact on fertility. The data do not provide direct evidence for endocrine disruption, hence other mechanisms should also be considered.

Keywords: Inuit; polymorphisms; reproductive health; semen quality; sex hormone receptors; time to pregnancy; xenobiotics.

Figure 1

Box plots showing lipid-adjusted serum concentrations of CB-153 and p,p′-DDE (ng/g serum lipid) in men (A, B) and women (C, D) in four regions. Values shown are median (line within box), 25th and 75th percentiles (bottom and top of box, respectively), 5th and 95th percentiles (lower and upper bars on whisker, respectively), and outliers (circles). Numbers below region labels indicate numbers of men or women who provided blood samples.

Figure 2

Box plots showing estrogenic (A, B), androgenic (C, D), and aryl hydrocarbon (dioxin-like, AhR; E, F) CALUX activities among men in four regions. For each receptor, agonistic assays are displayed on left panels (A, C, E) and competitive assays are displayed on right panels (B, D, F). Values shown are median (line within box), 25th and 75th percentiles (bottom and top of box, respectively), 5th and 95th percentiles (lower and upper bars on whisker, respectively), and outliers (circles). The dotted horizontal lines indicate the reference line. For agonistic assays, the reference line is solvent contol activity. For competitive assays, the reference line indicates competitive activity upon co-exposure to the natural (17β-estradiol) or synthetic ligands (the AR agonist R1881 and the AhR agonist TCDD) at a concentration of 40–50% of the concentration eliciting maximal response according to the assay-specific calibration curve (EC_40–50). For competitive assays, values above the reference line indicate enhancement of ligand activity and values below the line indicate competitive inhibition. Numbers below region labels indicate number of male measurements.