Dioxin and offspring sex ratios: Jongbloet et al.'s response. (Correspondence).

We are very pleased with James' comments on the sex ratio shifts after the dioxin disaster in Seveso (1) and his appreciation of our explanation of these phenomena. He mentions the disarray of results after exposure to organochlorine compounds and concludes that our and his own hormonal hypothesis "are not mutually exclusive" and that "both may be applicable, either separately or simultaneously." We like to stress, however, the added value and the parsimony of the overripeness ovopathy concept.

We agree that both hypotheses are concerned with the hormonal concentrations around the time of conception and that the antiestrogenic effects of the organochlorine compounds affect both paternal and maternal reproductive pathways. The increase of male-biased fetuses and subsequently (after having reached a critical threshold) the decrease due to loss of them, however, can only be understood by a dose-response fallacy. Nonoptimally matured oocytes--preferentially inseminated by Y-bearing spermatocytes and preferential loss of male fetuses--are supposed to be the key for elucidating this dose-response fallacy in mammals, including humans (1,2). This explains a) the mentioned disarray of varying and controversial results (either more sons or more daughters); b) the difficulties in reaching statistically significant results; c) the analogy with other high-risk conception categories in which the maturation of the oocyte is at stake (e.g., in very young and premenopausal mothers, in very short or unintendedly long interpregnancy intervals, in transitional stages between ovulatory and anovulatory seasons, etc.) (1,2); and d) the reduced quality of cumulus expansion, impaired maturation, fertilization, and embryonic development of porcine oocytes (3), besides the wide spectrum of reproductive disorders from menstrual disturbances, subfecundity, spontaneous abortions, stillbirths, and congenital malformations up to neurologic deficits in human progeny (4). This cluster of phenomena is not explained either by the prevailing theories or by James' hormonal hypothesis.

Piet Hein Jongbloet
Nel Roeleveld
Hans M.M. Groenewoud
Department of Epidemiology and
Biostatistics
University Medical Centre
Nijmegen, The Netherlands
E-mail: [e-mail]

REFERENCES AND NOTES

(1.) Jongbloet PH, Roeleveld N, Groenewoud HMM. Where the boys aren't: dioxin and the sex ratio. Environ Health Perspect 110:1-3 (2002).

(2.) Jongbloet PH, Zielhuis GA, Groenewoud HMM, Paskerde Jong PCM. The secular trends in male:female ratio at birth in postwar industrialized countries. Environ Health Perspect 109:749-752 (2001).

(3.) Campagna C, Sirard M-A, Ayotte P, Bailey JL. Impaired maturation, fertilization, and embryonic development of porcine oocytes following exposure to an environmentally relevant organochlorine mixture. Biol Reprod 65:554-560 (2001).

(4.) Ribas-Fito N, Sala M, Kogevinas M, Sunyer J. Polychlorinated biphenyls (PCBs) and neurological development in children: a systematic review. J Epidemiol Community Health 55:537-546 (2001).