Journal of Andrology, Vol. 28, No. 3, May/June 2007 Copyright E American Society of Andrology Impaired Semen Quality Associated With Environmental DDT Exposure in Young Men Living in a Malaria Area in the Limpopo Province, South Africa NATALIE H. ANECK-HAHN,*{ GLORIA W. SCHULENBURG,{ MARIA S. BORNMAN,{ PAULINA FARIAS,§ AND CHRISTIAAN DE JAGER* From the *Environmental Health, School of Health Systems & Public Health, and ÀAndrology, Department of Urology, University of Pretoria, Pretoria, South Africa, and `Department of Urology, University of Limpopo, Medunsa, South Africa; and §Instituto Nacional de Salud Publica, Cuernavaca, Morelos, Mexico. ABSTRACT: The pesticide DDT [1,1,1-trichloro-2,2-bis(chlorodi- cross-frequency (BCF) was higher with a higher p,p9-DDT concen- phenyl)ethane] is 1 of the 12 persistent organic pollutants (POPs) tration (b 5 0.01, P 5 .000). There was also a statistically significant under negotiation at the Stockholm Convention to restrict or ban positive association between percent sperm with cytoplasmic their production and use because of their toxicity, resistance to droplets and p,p9-DDT concentration (b 5 0.0014, P 5 .014). The breakdown, bioaccumulation, and potential for being transported ejaculate volume (mean 1.9 6 1.33 mL) was lower than the normal over long distances. DDT has estrogenic potential, and the main range ($2.0 mL) according to WHO, and a significant decrease with metabolite, p,p9-dichlorodiphenyl-dichloroethylene (p,p9-DDE), is increasing p,p9-DDE values was seen for both square root– a potent antiandrogen. In response to mounting evidence on the transformed volume (b 520.0003; P 5 .024) and count (b 5 endocrine-disrupting influence of environmental chemicals on human 20.003; P 5 .04). Although there were no associations between health, this epidemiological study was initiated to test the hypothesis either p,p9-DDT or p,p9-DDE concentrations and the rest of the that nonoccupational exposure to DDT affects male reproductive seminal parameters, the incidence of teratozoospermia (99%; parameters. In a cross-sectional study, healthy male subjects (n 5 normal sperm ,15%) was high. Twenty-eight percent of the study 311) between 18 and 40 years (23 6 5) of age were recruited from 3 group presented with oligozoospermia (,20 6 106 sperm/mL), communities in an endemic malaria area in which DDT is sprayed which had a significant positive association with p,p9-DDE (odds annually. A semen analysis according to World Health Organization ratio [OR] 5 1.001, P 5 .03). There was a significant positive (WHO) standards was performed. The Hamilton Thorne Computer association between participants with asthenozoospermia (32%) and Assisted Sperm Analysis (CASA) system was simultaneously used p,p9-DDT (OR 1.003, P 5 .006) and p,p9-DDE (OR 1.001, P 5 .02). to determine additional sperm motility parameters. Blood plasma The results imply that nonoccupational exposure to DDT is samples were assayed for p,p9-DDT and metabolites as a measure associated with impaired seminal parameters in men. The high of exposure. The exposure levels were expressed as lipid-adjusted exposure levels of p,p9-DDT and p,p9-DDE are of concern because p,p9-DDT and p,p9-DDE values. The mean p,p9-DDT and p,p9-DDE these levels could have far-reaching implications for reproductive concentrations were 90.23 mg/g(6102.4) and 215.47 mg/g(6210.6), and general health. respectively. The multivariate linear regression analyses indicated Key words: Seminal parameters, organochlorine pesticides, p,p9- that mean CASA motility was lower with a higher p,p9-DDE DDT, p,p9-DDE, POPs, spermatozoa, CASA. concentration (b 520.02, P 5 .001) and the CASA parameter beat J Androl 2007;28:423–434 he Stockholm Convention resulted from a decision cals. The convention initially targeted 12 chemicals T made in 1995 by the United Nations Environment known as persistent organic pollutants (POPs), arguing Programme Governing Council (UNEP) to develop that those chemicals pose major and increasing threats a legally binding instrument to control certain chemi- to human health and the environment (UNEP, 1995). The Stockholm Convention on POPs became legally binding on May 17, 2004. The Convention is a global The National Research Foundation (NRF) and the Medical multilateral agreement with the aim of protecting Research Council (MRC), South Africa funded this study. Correspondence to: C de Jager, PhD, Environmental Health, School human and environmental health from the effects of of Health Systems & Public Health, University of Pretoria, PO Box 667, exposure to specific POPs. Restricting the use and Pretoria, 0001, South Africa (e-mail: [email protected]). production of these chemicals or banning them will, Received for publication September 29, 2006; accepted for when the measures of the convention are successfully publication December 18, 2006. The authors declare no financial or personal conflicts of interest that implemented, reduce the hazards posed by these might affect any aspect of this study. pollutants. Although South Africa ratified the Conven- DOI: 10.2164/jandrol.106.001701 tion on September 4, 2002 (Bouwman, 2004), it has 423 424 Journal of Andrology N May ÙJune 2007 applied for exemption as far as the use of DDT [1,1,1- endocrine-disruptive environmental pollutants (Turusov trichloro-2,2-bis(chlorodiphenyl)ethane] for malaria et al, 2002). Serum levels of p,p9-DDE are an integrated vector control is concerned. measure of internal dose, reflecting exposure from all POPs are organic compounds that, to a varying sources over the previous years (Hauser et al, 2003). degree, resist photolytic, biological, and chemical Reproductive disorders were among the first adverse degradation. These compounds are often halogenated effects linked to organochlorine exposure (Beard, 2005). and characterized by low water solubility and high lipid Reproductive abnormalities attributed to DDE expo- solubility. They are also semivolatile, enabling them to sure after a major pesticide spill in 1980 were found in move long distances in the atmosphere before deposition reptiles inhabiting Lake Apopka in Florida in the 1990s. occurs. POPs, which are noted for their persistence and The types of deformities found were ambiguous gonads bioaccumulative characteristics, include DDT, dieldrin, (ovotestes) in turtles and abnormal sex hormone levels, toxaphene, chlordane, and several industrial chemical poorly organized testes, and small penises in male products and byproducts, including polychlorinated alligators (Guillette et al, 1995). The Great Lakes fish biphenyls (PCBs), dioxins, and furans (UNEP, 2006). found to be contaminated with organochlorine com- DDT and similar stable chlorinated compounds can pounds such as PCBs, dioxins, DDT metabolites, and be transported via air, rivers (Rawn et al, 1999; Buehler dibenzofuran have exhibited reproductive and other et al, 2004), and ocean currents (Bidleman et al, 1995) endocrine abnormalities. Wildlife (birds, turtles, and over long distances and have been detected in the mammals) that have consumed these fish have also Antarctic and other areas, far from their production exhibited various abnormalities, which include impaired sites or regions of use (Bouwman, 2004). While DDT is reproduction, same-sex pairing, feminization, ambiguous targeted by the treaty, exemptions are available for genitalia, and reduced fertility (Colborn et al, 1993, 1996; countries that are still using DDT to combat malaria. Fry, 1995). In mice, the uterotrophic effect of DDT The treaty mobilizes much needed funding to help increased the weight of the uterus and the development of countries shift to safer alternatives for malaria control, a pseudouterus (Morozova et al, 1997). A permanent, which has drawn attention and resources to the ongoing functional male-to-female sex reversal following a single and long-ignored tragedy of malaria, particularly in exposure of eggs to o,p9-DDT was observed in medaka Africa. A small group of United States conservatives fish (Edmunds et al, 2000; Turosov et al, 2002). There is continues to push to re-establish DDT as a ‘‘safe’’ also evidence that DDT acts as a promoter of mammary chemical for use against malaria, despite a clear decision tumors in rats and that it can inhibit gap junctional by the international community that DDT should be intercellular communication (Snedeker, 2001). Other targeted for ultimate elimination (Pesticide Action evidence of hormone-disrupting effects of DDT and its Network North America). All these factors have made metabolites has included reproductive defects and egg- the continued use of DDT for malaria vector control in shell thinning in avian species (Fry, 1995; Snedeker, South Africa, Africa, and all the other countries that 2001). DDT or p,p9-DDE might alter sex hormone have applied for exemption a matter of global interest. metabolism, reducing available testosterone to tissues A number of reports have indicated that, in addition (Guillette et al, 1995). to being toxic, organochlorine pesticides, including In humans, a trend in decreasing human sperm count DDT and its metabolites, might act as endocrine might have occurred in several European regions during disruptors (Turusov et al, 2002). Endocrine-disrupting the last 50 years (Irvine, 1994; Auger et al, 1995; Toft et chemicals can be defined as compounds that influence al, 2004). The decrease in sperm count is paralleled by normal hormone functions, generally causing adverse a rise in the trend of testicular cancer and malformations effects (Godduhn and Duffy, 2003). Technical-grade of the male reproductive organs such as hypospadias DDT is a mixture of p,p9-DDT (,85%), o,p9-DDT and cryptorchidism (Toppari et al, 1996). Skakkebaek et (,15%), and o,o9-DDT (trace amounts), with both p,p9- al (2001) presented a hypothesis that poor semen DDT and o,p9-DDT having estrogenic activity. p,p9- quality, testicular cancer, cryptorchidism, and hypospa- Dichlorodiphenyl-dichloroethylene (p,p9-DDE), a persis- dias are all indicative of 1 underlying entity—testicular tent metabolite of p,p9-DDT, is a widespread environ- dysgenesis syndrome (TDS)—with an origin in fetal life.