Parental exposure to dioxin and offspring sex ratios.

I would like to respond to the comments of Jongbloet et al. (1) on the data of Mocarelli et al. (2). Mocarelli et al. (2) reported on the offspring sex ratios (proportions male) following the explosion at Seveso, Italy, that released 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD, dioxin) into the environment. Mocarelli et al. (2) categorized matings into the four possible combinations by sex and exposed versus unexposed. Their analysis yielded one unequivocal result and one equivocal one: a) exposed men mated to unexposed women produced offspring with a a significantly low sex ratio; and b) exposed women mated to unexposed men produced offspring with a nonsignificantly high sex ratio. Jongbloet et al. (1) explained both of these phenomena by their hypothesis of preovulatory and postovulatory overripeness, and they claimed that it is more plausible than my hormonal hypothesis (3). Because I had predicted that exposed men would sire an excess of daughters (3), my hypothesis—at least initially—seemed preferable. However, it now seems that these theories (both theirs and mine) may be premature: paternal exposure to organochlorine compounds has been reported to be followed by significant excesses of daughters (2,4), a nonsignificant excess of sons (5), and a significant excess of sons (6). This disarray may be potentially explained in several ways: • The various organochlorine compounds may actually have different effects on the offspring sex ratio of exposed men. This may not be accurate because opposite effects have been reported in respect of dioxin itself. • The organochlorine compounds may have opposite effects on exposed mothers and exposed fathers, thus suggesting the possibility of confounding. However, both Mocarelli et al. (2) and Karmaus et al. (6) assessed paternal and maternal exposures and yet reached opposite conclusions (admittedly in one case on TCDD and in the other on polychlorinated biphenyls). • It is possible that the different exposures may have been to different congeners and/or contaminants and that these contaminants had causal effects. Logically, Jongbloet’s hypothesis and mine are not mutually exclusive: both may be applicable, either separately or simultaneously. I subscribe to the appeal of Jongbloet et al. (1) for more research on the effects of organochlorine compounds on mammalian offspring sex ratios, and I welcome their predictions. William H. James The Galton Laboratory University College London London, England Fax: 44-207-383-2048