Apolipoprotein E (ApoE) polymorphism is related to differences in potential fertility in women: a case of antagonistic pleiotropy?

The alleles that are detrimental to health, especially in older age, are thought to persist in populations because they also confer some benefits for individuals (through antagonistic pleiotropy). The ApoE4 allele at the ApoE locus, encoding apolipoprotein E (ApoE), significantly increases risk of poor health, and yet it is present in many populations at relatively high frequencies. Why has it not been replaced by natural selection with the health-beneficial ApoE3 allele? ApoE is a major supplier of cholesterol precursor for the production of ovarian oestrogen and progesterone, thus ApoE has been suggested as the potential candidate gene that may cause variation in reproductive performance. Our results support this hypothesis showing that in 117 regularly menstruating women those with genotypes with at least one ApoE4 allele had significantly higher levels of mean luteal progesterone (144.21 pmol l(-1)) than women with genotypes without ApoE4 (120.49 pmol l(-1)), which indicates higher potential fertility. The hormonal profiles were based on daily data for entire menstrual cycles. We suggest that the finding of higher progesterone in women with ApoE4 allele could provide first strong evidence for an evolutionary mechanism of maintaining the ancestral and health-worsening ApoE4 allele in human populations.

Interpopulation, interindividual, intercycle, and intracycle natural variation in progesterone levels: a quantitative assessment and implications for population studies.

Methodological challenges in studying sex steroid hormones in premenopausal women result from the existence of variation at three levels: among women from the same population, among menstrual cycles recorded for women at different times of the year, and among days of the same cycle. We partitioned, for a Polish rural population, the natural, nonpathological, variation in salivary progesterone concentrations (measured during 14 days of the luteal phase) into the intracycle component (which accounts for 65% of the total variation) and the among-cycle component (the remaining 35% of the total variation). Out of the among-cycle variation in salivary progesterone, as much as 46% is expressed as differences among individual women (interindividual component); the remaining 54% of variation is due to differences among cycles of individual women (intercycle, within-women component). Such intercycle variation is probably caused by a seasonality of agricultural workload and is much higher than in nonseasonal, industrial populations. We also used bootstrap analyses to generate heuristic recommendations for choosing sample sizes of the number of subjects, number of cycles per woman, and number of days per cycle. Studies in populations with seasonal lifestyles should rely on measurements of at least three cycles per woman. Given the substantial intracycle amplitude in hormone levels to reliably assess biologically and medically relevant variation in ovarian function, at least 7-8 days/cycle should be measured.

Daughters increase longevity of fathers, but daughters and sons equally reduce longevity of mothers.

Reproduction is energetically and physiologically expensive, and an individual investing resources into producing offspring should suffer costs such as deterioration in health condition and possibly shorter life span. Since the energetic and nutritional demands of pregnancy and breastfeeding render reproductive costs much higher in women than in men, women with a large number of children should show signs of deterioration in condition, while men with large families should not. However, whether reproductive costs reduce longevity in women is still questionable, and in men this issue has not been adequately addressed. In addition, since sons are energetically more expensive to produce than daughters, having sons should have a more pronounced negative impact on maternal longevity than having daughters. Here we document a striking disparity in the impact of children on the life span of mothers and fathers in a Polish rural population. We show for the first time that number of daughters was positively related to a longer life span of their fathers, increasing their longevity on average by 74 weeks per daughter born, while number of sons did not have a significant effect on paternal longevity. In contrast, in women, the number of daughters and number of sons reduced maternal longevity and did so to the same extent, on average by 95 weeks per son or daughter, indicating that for women, the costs of having sons and daughters are similar.