Where the boys aren't: dioxin and the sex ratio.

The question of how exposure to dioxins might affect only males and why it affects preferentially male embryos in the Seveso data presented by Mocarelli et al. remains intriguing. This enigma can be explained by the ovopathy concept, which addresses the determination of both the sex and the condition of the progeny. Antiandrogenic properties of dioxin alter the sperm-transit time and mating behavior, which provoke delay of fertilization of the oocyte (postovulatory overripeness of the oocyte). Antiestrogenic properties of dioxin during mid-cycle compromise both mucus liquefaction and maturation of the oocyte (preovulatory overripeness ovopathy). A positive dose-response of male-biased pathologic conceptuses is often followed by a negative one due to "vanishing male conceptuses." This dose-response fallacy is present in animal experiments and explains many otherwise unexplained phenomena related to dioxin contamination and other high-risk conceptions.