The Sex Ratio of Offspring of Men Exposed to Metal Fumes

William H James

The Galton Laboratory, University College London, Wolfson House, 4 Stephenson Way, London NW1 2HE, UK

Figa-Talamanca and Petrelli1 report that men exposed to metal fumes have low offspring sex ratios (proportions male) at birth. They divide their workers into four graded categories of exposure (no exposure ... highly exposed) and note that the two extreme offspring sex ratios are highly significantly different from one another. However one is left wondering about an overall assessment of their data in toto. For this purpose I performed a Mann-Whitney test. The resulting z-score (corrected for ties) took the value of 2.57, P = 0.005. So overall, there is a highly significant trend in these data, suggesting that paternal exposure to metal fumes is associated in a dose-related fashion with the production of excess daughters.

The authors mention two alternatives in this context, viz that

  1. exposure alters men's hormone profiles, and that—in accordance with my hypothesis2—these directly affect the sex ratio at conception, and
  2. exposed men somehow cause their wives to have male-biased spontaneous abortions.

In the context of my hypothesis, the authors mention that Bonde et al.3 reported poor semen and low fertility in welders, but no low offspring sex ratio. I should emphasize that ex hypothesi offspring sex ratio is to be regarded as a marker for unusual (pathological) hormone profiles—not as a marker for abnormal levels of individual hormones. Jacobsen et al.4 reported a normal sex ratio in the offspring of men ascertained at a sperm analysis clinic. So if offspring sex ratio is considered as a test, it will sometimes (as in the data of Bonde et al.3) give a false negative result, but it has not (to my knowledge) been reported to give a false positive one. In other words an unusual sex ratio may be presumed indicative of parental hormone imbalance: whereas a normal sex ratio may exist in spite of parental endocrine pathology (e.g. overall high or low hormone levels). The rationale for using offspring sex ratio as a marker for endocrine pathology is that it is useful, rapid and non-invasive; it may reflect the effects of low-level, long-term exposure; and ex hypothesi, it may be a permanent witness to hormone imbalance many years in the past. It is not a substitute for invasive testing (e.g. of sperm or endocrines) but may sometimes suggest that such procedures would be appropriate.

I should like to suggest that the authors follow up their alternatives elaborated above by considering the following questions:

  1. Do the exposed men have—as I would hypothesize—low T/G ratios (where T and G are respectively a man's standardized testosterone and gonadotrophin levels)? If these data are not immediately available, I suggest that hormone assays would now be justified (at least of the founders). An explanation of the founders' unusual offspring sex ratio is now needed. Is it indicative of serious reproductive hazard?
  2. Do the wives of exposed men (particularly founders) report a high incidence of spontaneous abortion? If so, is there a dose-related association between the incidence of abortion and level of exposure?

References

1 Figa-Talamanca T, Petrelli G. Reduction in male births among workers exposed to metal fumes. Int J Epidemiol 2000;29:381.[Free Full Text]

2 James WH. Evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels at the time of conception. J Theor Biol 1996;180:271–86.[ISI][Medline]

3 Bonde JPE, Olsen JH, Hansen KS. Adverse pregnancy outcome and childhood malignancy with reference to paternal welding exposure. Scand J Work Environ Health 1992;18:169–77.[ISI][Medline]

4 Jacobsen R, Bostofte E, Skakkeback NE, Hansen J, Moller H. Offspring sex ratio of subfertile men and men with abnormal sperm characteristics. Hum Reprod (In press), 2000.


 

Authors' Response

Irene Figa-Talamanca

Department of Biology, University of Rome, ‘La Sapienza’, 00185 Rome, Italy

Sir—We thank Dr. James for his useful comments and reinforcing our hypothesis about the potential role of unusual sex ratio as an indicator of environmentally induced hormone imbalance at the population level. Regarding his suggestion for further study, we answer as follows:

  1. our data derive from a study of past reproductive experience and past occupational exposures. We are not in a position to reconstruct hormone profiles of these men. We are exploring the possibility of evaluating such profiles of presently exposed founders, in an attempt to provide an explanation of the unusual sex ratio observed.
  2. The incidence of recognized spontaneous abortion among wives of exposed men was not higher than incidence of the non exposed (13.8% vs. 16%). This could be interpreted as evidence in favour of the hypothesis that the alterned sex ratio might be the result of male hormonal interference rather than increased male-biased spontaneous abortions.





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