Hum. Reprod. Advance Access originally published online on June 28, 2007
Human Reproduction 2007 22(10):2792; doi:10.1093/humrep/dem193
Letters to the Editor |
Maternal lead exposure, secondary sex ratio and dose-exposure fallacy
Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
1 Correspondence address. Tel: +31-024-3619132; Fax: +31-024-3613505; E-mail: p.jongbloet{at}epib.umcn.nl
Jarrell et al. (2006)
conclude that they did not find evidence for an association between maternal and fetal lead exposure and lower secondary sex ratio among newborns in a large sample in Mexico City. The odds ratio for a male child initially increased by quintile of maternal blood lead concentration and then decreased, despite more exposure. To them, this result appears to be in contrast with reduced proportions of male births in several examples of maternal exposures to other environmental chemicals. The authors refer to changes in the sex ratio postulated by us to represent pathology involving the conceptus, and more specifically the variable rate of occult loss of male embryos (Jongbloet et al., 2001, 2002). Although they assert that lead exposure has been associated with overt spontaneous abortion, they feel that their findings do not suggest an association between relatively high levels of environmental lead exposure and a reduction in the proportion of male births.
The increase in the odds ratio of male births up to the third quintile of maternal blood lead concentration, apparent in the Fig. 1 of their article and to a lesser extent in the three figures that follow (Figs 2–4), related to other biomarkers (cord lead concentration, maternal patella and tibia bone lead) seems to us but illustrations of what the over-ripeness ovopathy concept predicts (Jongbloet, 2004): the increase is due to preferential fertilization of non-optimally matured oocytes by Y-bearing sperm in a dose–response fashion, but after having reached a certain plateau, inversion occurs to male-biased loss of fetuses before birth, either occult or overt, as a result of non-optimal embryo development, inherent ill-implantation and fetal arrest. A decrease in the secondary sex ratio does not necessarily imply sex reversal, but still represents a dose–response fallacy, as evident in the decline in the sex ratio over the past half century and among decreasing socio-economic income categories. This interpretation could be substantiated by comparison of the rate of male preponderance among the overt abortuses in the increasing quintiles of lead exposure.
References
Jarrell JF, Weiskopf MG, Weuve J, Téllez-rojo MM, Hu H, Hernàndez-Avila M. Maternal lead exposure and the secondary sex ratio. Hum Reprod (2006) 21:1901–1906.
Jongbloet PH. Over-ripeness ovopathy—a challenging hypothesis for sex ratio modulation. Hum Reprod (2004) 19:769–774. 1036–1038.
Jongbloet PH, Zielhuis GA, Groenwoud HM, Pasker-De Jong PC. The secular trends in male:female ratio at birth in pastwar industrialized countries. Environ Health Perspect (2001) 109:749–752.[Web of Science][Medline]
Jongbloet PH, Roeleveld N, Groenewoud HM. Where the boys aren't: dioxin and the sex ratio. Environ Health Perspect (2002) 110:1–3.[Web of Science][Medline]
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