DDT and DDE: effect on second generation time to pregnancy.

Cohn BA, Cirillo PM, Wolff MS, Schwingl P J, Cohen RD, Sholtz RI, Ferrara A, Christianson RE, van den Berg BJ, Siiteri PK. 2003. DDT and DDE exposure in mothers and time to pregnancy in daughters. Lancet 361:2205-2206.

Reproductive tract anomalies have been seen in daughters of women who took the potent estrogenic chemical diethylstilbestrol during pregnancy to prevent morning sickness. Knowing this, NIEHS grantee Barbara Cohn at the Public Health Institute in Berkeley, California, and colleagues decided to investigate whether in utero exposure to weakly estrogenic chemicals, including the insecticide DDT and its metabolites, might produce similar adverse reproductive effects.

The World Health Organization estimates that during the period of DDT's use approximately 25 million lives were saved, predominantly from malaria and typhus. However, many species of insects developed resistance to DDT, it proved to be highly toxic toward fish, and it was responsible for the near-extinction of several bird species because of its interference with the formation of egg shells. For these reasons and because of its environmental persistence, the use of DDT was banned in the United States in 1972. However, DDT is still used in some parts of the world.

In mammals, DDT and its major metabolite, DDE, persist in the body and are stored in fat tissue. DDT is known to have weak estrogenic activity, and DDE has considerable antiandrogenic activity. They can cross the placenta, potentially interfering with fetal development.

To further investigate possible effects on the human reproductive system, Cohn's team measured DDT and DDE concentrations in maternal serum samples collected during 1960-1963. The samples were collected within 1-3 days of delivery from women enrolled in the Kaiser Permanente health plan who were participating in the Child Health and Development Studies. The researchers then compared these levels to the time until pregnancy (measured by survey) for 289 daughters of these women.

There was a clear association between increased DDT concentrations in maternal blood and a decreased chance of pregnancy in the daughters. For every 10 milligrams per liter of DDT in maternal serum, the probability of pregnancy dropped 32%. However, quite unexpectedly, the chance of pregnancy increased 16% with each increase of 10 milligrams per liter of DDE.

The opposing effects of DDT and DDE may explain why large changes in reproductive performance overall have not been noticed in humans since the introduction of DDT. Although the decreased fertility associated with in utero exposure to DDT remains unexplained, the authors speculate that the "antiandrogenic effects of DDE may mitigate harmful androgenic effects on the ovary during gestation and early life."

This study, the first to link DDT exposure in utero to human reproductive problems some 30 years later, demonstrates the long delay from exposure to noticeable effect. The findings support the establishment of new long-term human studies that can monitor the effects of environmental exposures on reproduction, as well as continued support of existing studies where multigenerational follow-up is in progress.