The male disadvantage and the seasonal rhythm of sex ratio at the time of conception: Reply

Angelo Cagnacci

Department of Obstetrics Gynecology and Pediatric Sciences, Gynecology Unit, Policlinico di Modena,via del Pozzo 71, 41100, Modena, Italy. e-mail: cagnacci{at}unimore.it

Dear Sir,

We are sorry that the data and the conclusions of our manuscript (Cagnacci et al., 2003Go) are considered embarrassing by some researchers looking into modulation of sex ratio, but we are pleased to have the opportunity of clarifying some issues raised by Dr Jongbloet in his letter.

Dr Jongbloet states that our conclusions contrast the well-known V shaped probability of delivery male offspring at both the onset and at the end of the fertile window of the menstrual cycle. The parallelism between a seasonal environmental modification favouring reproduction and the modifications occurring within a single menstrual cycle is rather hazardous, since different mediators can be involved. Beside this, the V-shaped probability is perhaps not ‘well known’, since others (Shettles and Rorvik, 1984Go) have reported a probability different from the one described by Dr Jongbloet, and several studies have not found any evidence of a difference in sex ratio for conceptions occurring across the menstrual cycle (Bernstein, 1995Go; Wilcox et al., 1995Go; Gray et al., 1998Go). Dr Jongbloet sustains this hypothesis with a further hypothesis based on a single marginal piece of evidence: i.e. that the reduced volume of Y-bearing sperm makes them more capable of penetrating the unfavourable mucus in conditions characterized by difficult ovulation. This is a purely speculative assertion that unduly simplifies the complexity of the fertility process, which also involves sperm metabolism, sperm energy store, intravaginal and intrauterine sperm survival, sperm capacitation, sperm acrosome reaction, sperm hyperactivation, sperm interaction with cumulus oophorus and zona pellucida, ovum fertilization, embryo division, embryo metabolism, embryo implantation, and embryo survival.

Dr Jongbloet states that his theory is further supported by the clear increase of sex ratio in aged mothers of animals. The object of our study is the human and Dr Jongbloet omits to mention that human data do not show an increase of sex ratio among births from ageing mothers (James, 1996Go). By contrast, and in accordance with our hypothesis, aged women show a reduction of sex ratio in their offspring (Juntunen et al., 1997Go; Orvos et al., 2001Go).

The concept that an optimal progeny is associated with peaks of reproductive performance, and a more disabled progeny with the transitional stages of the ovulatory pattern, is not completely clear. Reproductive breakthrough and breakdown, where non-optimal maturation of the oocyte brings the so-called pre-ovulatory overripeness ovopathy, may apply to seasonal breeders, in which an ovulatory pattern becomes anovulatory and vice versa, but it is unclear how this applies to women. Women continue to ovulate throughout the year, and whether a non-optimal oocyte maturation does occur, this non-optimal maturation should be more represented in the period of minimal fecundity than in the transitional periods. Even if applicable to women, the concept that a more disabled progeny is present in the transitional reproductive periods is not in contrast with our findings, unless males are considered a disabled progeny. Males are more fragile than females, but the parallelism between male sex selection and disabled progeny does not seem appropriate.

In his letter, Dr Jongbloet perhaps generalizes his concept, not making any distinction between time of conception and time of birth. They are not the same, and in the human they are separated from each other by 9 months. This should be taken into consideration when comparing our data with those of the literature. For example Dr Jongbloet maintains that all the data (at birth) indicate a prevalence of males in transitional periods. Although this does not clearly emerge from the literature, it can be expected that, whether our data at conception are correct, a sex ratio biased towards males can become evident 9 months later, i.e. at birth. This time coincides with the transitional reproductive period, corresponding to what Dr Jongbloet calls the breakthrough of the ovulation rate. Accordingly, our data seem in line with the existing literature.

Dr Jongbloet mixes animal and human data. We think that our data cannot be generalized to all species, for three reasons.

(i) Determinants of sex ratio, like determinants of conception, may act as proximate or ultimate factors. In the first case, determination refers to time of conception, in the second case to the time of birth (Bronson and Heidman, 1994Go). Whether a factor acts as ultimate or proximate determinant may vary among species (Bronson and Heidman, 1994Go). Only our group has evaluated sex ratio of viable pregnancies at the time of conception in the human species. The data show a clear seasonal rhythm of sex ratio, which is not so clear when the same data are evaluated at the time of birth. This is consistent with previous data at birth (James, 1996Go; Jongbloet et al., 1996Go; Maconochie and Roman, 1997Go), and seems to suggest that seasons act as a proximate rather than ultimate factor in the determination of human sex ratio.

(ii) Time between conception and birth varies among species, and in some short-lived species conception and birth may occur in the same season. This makes a huge difference when data that are modulated at conception are analysed at birth.

(iii) Interpreting animal data as a whole is rather complex and requires a careful evaluation of many variables that influence sex ratio differently. Among animals, the relative proportion of the two sexes is linked to the mating system, the social organization and the ranking position of each single animal. In some species, sex ratio at birth is biased towards females rather than males (Rothe et al., 1992Go). Social ranking of parents may influence sex ratio (Meikle et al., 1984Go; Gomendio et al., 1990Go), and different social organization and mating systems (polgyny, polyandry, multimale–multifemale or gregarious) (Dixon, 1998Go) may not require an equal number of males and females at time of reproduction (Wong and Ni, 2000Go). Accordingly, we feel that the mechanisms modulating sex ratio in humans cannot be extrapolated to species living with a different social organization and a different mating system.

Dr Jongbloet has reinterpreted our data, imagining a double hump surge in the period of his interest and has adjusted our conclusions. He sees two transitional periods, one in May (breakthrough of ovulation rate) and the other in August (breakdown of ovulation rate) which are separated by only 2 months (June and July) of favourable reproductive conditions. By contrast, in his reading the unfavourable reproductive period lasts 7 months (October–April). This is not the case. The data on conception rate show a sinusoidal rhythm, with a period of 12 months, and two roughly equal periods of high and low fecundity. Accordingly, the two transitional periods should be 6 months apart from each other, and also the two peaks of sex ratio should be 6 months apart from each other. By contrast, a cosinor analysis sex ratio shows a sinusoidal rhythm, in phase with that of conception and characterized by a single peak in October. We appreciate the comments of Dr Jongbloet, but in our opinion, our data simply do not seem to fit his hypothesis.

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