J. theor. Biol. (1999) 197, 261–263Article No. jtbi.1998.0884, available online at http://www.idealibrary.com on

0022–5193/99/006261+03 $30.00/0 7 1999 Academic Press

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Further Evidence Relating Offspring Sex Ratios to Parental HormoneLevels Around the Time of Conception

1. Introduction

I have previously suggested that mammalian(including human) sex ratios at birth are partiallycontrolled by the hormone levels of both parentsaround the time of conception (James, 1996).The present note offers further evidence locatedsince submission of that paper.

2. Men Exposed to Borates

Boron has been reported to have adverseeffects on the male reproductive system; theseeffects have included oligospermia, decreasedlibido (Krasovskii et al., 1976) and sterility(Tarasenko et al., 1972). Whorton et al. (1994)cited a number of experimental studiessuggesting that borates cause testicular atrophyin rats, mice and dogs. Lastly the hormonaleffects of boron on rats were reportedly increasedgonadotrophin levels (Lee et al., 1978) anddecreased testosterone levels (Treinen & Chapin,1991). This hormone profile (reduced testoster-one and increased gonadotrophin) has beenhypothesized to cause men to sire an unusuallyhigh proportion of daughters (James, 1996).Whorton et al. (1994) reported that men exposedto borates sired 250 sons and 279 daughters. Theexpected U.S. live birth sex ratio (proportionmale) was 0.512 and x2 =3.3, pQ 0.05, one-way.Thus these data give some support to thehypothesis.

3. People Exposed to Dioxins

Egeland et al. (1994) reported that menexposed to dioxins have significantly highgonadotrophin and low testosterone levels as

contrasted with controls. Noting that thishormone profile has been hypothesized to beassociated with low offspring sex ratios, Ipredicted that men exposed to dioxins would sirean excess of daughters (James, 1995). Thisprediction has since been confirmed. A signifi-cant and substantial diminution in sex ratio wasreported among the births to people who werecontaminated with dioxins by the Seveso disasterin 1976 (Moccarelli et al., 1996).

It would be interesting to know:

(a) the sexes of offspring of parents in whomonly the mother had been exposed, and

(b) the hormonal effects of dioxin on women.

In any case, these data give further support to thehypothesis.

4. The Waist/Hip Ratio

In recent years, the waist/hip (W/H) ratio hasemerged as an important measure in medicalscience. Singh (1993) cited papers suggesting thata high W/H ratio is associated with latemenarche, high hyperandrogenism, high risks fortype II diabetes, gallbladder disease, cancers ofthe ovary, endometrium and breast, hyperten-sion, heart disease and stroke. Many of theseassociations may be presumed to be due to theestablished positive association between W/Hratio and testosterone levels in both men andwomen.

I have hypothesized that parental testosteronelevels around the time of conception areassociated with the sexes of the resultingoffspring, high levels (in either parent) beingassociated with subsequent boys (James, 1996).If that were correct, then W/H ratio (in both men

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and women) should correlate positively with thesex ratio (proportion male) of their offspring.Two studies have confirmed this suggestionin women (Manning et al., 1996; Singh &Zambarano, 1997): although it must beacknowledged that unpublished data of Zaadstrashow no such relationship in 191 Dutch births.

It would be interesting to see whether (as Iwould predict) the W/H ratio of fathers (as well,apparently, as of mothers) correlates with the sexratio of their children.

5. Rheumatic Diseases and HLA Genes

A number of rheumatic diseases [e.g. rheuma-toid arthritis (RA), and such HLA B 27-relateddiseases as Reiter’s syndrome (RS) and ankylos-ing spondylitis (AS)] are thought to be partiallycaused by respectively low and high circulatinglevels of testosterone (T) (James, 1991, 1993). Ithas also been found that HLA genes correlateswith T levels in men (Ollier et al., 1989) andwomen (Gerencer et al., 1982). It seems likelythat there is a causal relationship here such thatthe HLA genes are directly coding for gonadalsize and consequent hormone level and diseaseassociations as predicted by Ivanyi et al. (1972).If this were so, and if my hypothesis were correct,a number of consequences would follow viz:

(1) there would be unusual sex ratios infamilies of probands with these diseases,

(2) the frequencies of the relevant HLA geneswould not be equal in the two sexes, and

(3) since the genes which code for high Tlevels in one sex do not, in general, codefor high T levels in the other sex, onewould expect the strengths of the associ-ations between the genes and the diseasesto differ in the two sexes.

Only the first of these points will be treatedhere. I reviewed data on the sexes of the sibs ofprobands with RA, AS and RS (James, 1991).Probands with RA had an excess of sisters; whilethose with RS and AS had excesses of brothers.Since, these data had been collected for otherpurposes, it was not easy to assess thesignificance of these biased sex ratios. However,confirmation for them has since been publishedby Calin et al. (1993), Ploski et al. (1994) and

Deighton et al. (1993). It seems reasonable tointerpret these studies as providing confirmatorydata for my hypothesis.

I am grateful to Dr B. M. Zaadstra (Leiden,Holland) for responding to a request for data.

W H. JThe Galton Laboratory,

University College London,Wolfson House,

4 Stephenson Way,London NW1 2HE, U.K.

(Received on 9 October 1996, Accepted on 28 July1997)

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