Natural selection and sex differences in morbidity and mortality in early life

Both morbidity and mortality are consistently reported to be higher in males than in females in early life, but no explanation for these findings has been offered. This paper argues that the sex difference in early vulnerability can be attributed to the natural selection of optimal maternal strategies for maximizing lifetime reproductive success, as modelled previously by Trivers and Willard. These authors theorized that males and females offer different returns on parental investment depending on the state of the environment. Natural selection has therefore favoured maternal ability to manipulate offspring sex in response to environmental conditions in early life, as shown in variation in the sex ratio at birth. This argument can be extended to the whole period of parental investment until weaning. Male vulnerability in response to environmental stress in early life is predicted to have been favoured by natural selection. This vulnerability is most evident in the harsh conditions resulting from pre-term birth, but can also be seen in term infants, and manifests as greater morbidity and mortality persisting into early childhood. Malnutrition, interacting with infection after birth, is suggested as the fundamental trigger mechanism. The model suggests that whatever improvements are made in medical care, any environmental stress will always affect males more severely than females in early life.     

A simple model for adaptive variation in the sex ratios of mammalian offspring

We present a simple mathematical model that describes how primary and secondary sex ratios of offspring may vary adaptively in order to maintain equal numbers of the sexes at the age of reproductive maturity. The model postulates that the sex of an offspring depends probabilistically on a weighted linear combination of maternal testosterone and male vulnerability. The model operates at population level, and is based on three physiological phenomena: first that maternal testosterone in follicular fluid is normally distributed, with levels above the mean more likely to be associated with the conception of males; secondly, that males are more vulnerable than females from conception onwards; and thirdly that under conditions of chronic stress, increased secretion of female testosterone coincides with increased male vulnerability. Thus during times of chronic stress, more males are conceived, but their number of live births is moderated by increased male loss. Variations in secondary sex ratios should therefore be related not only to the stressfulness of environmental conditions, but also to the timing of changes in stressfulness.     

Sex differences in the prevalence of human birth defects: a population-based study.

BACKGROUND: Sex differences in the prevalence of several human birth defects have often been reported in the literature, but the extent of sex differences for most birth defects is unknown. To determine the full extent of sex differences in birth defects in a population, we examined population-based data from the Metropolitan Atlanta Congenital Defects Program (MACDP). METHODS: MACDP records were analyzed for 1968 through 1995. We determined the sex-specific prevalence of all major birth defects, using the total number of live births by sex during these years as the denominator. For each specific defect, we calculated a relative risk with regard to sex on the basis of the ratio of prevalence among males to prevalence among females. Male-female relative risks were also determined for total major birth defects and for several broad categories of defects. RESULTS: The overall prevalence of major defects at birth was 3.9% among males and 2.8% among females. All but two of the major categories of birth defects (nervous system defects and endocrine system defects) had a higher prevalence among males. Defects of the sex organs were eight and one-half times more prevalent among males and accounted for about half of the increased risk of birth defects among males relative to females. Urinary tract defects were 62% more prevalent among males, and gastrointestinal tract defects were 55% more prevalent among males. Among specific defect types, twofold or greater differences in prevalence by sex were common. CONCLUSIONS: Our data indicate that sex differences in the prevalence of specific human birth defects are common, and male infants are at greater risk for birth defects than female infants. Several mechanisms have been proposed to account for these differences.     

Maternal Investment of the Virunga Mountain Gorillas

The Trivers & Willard hypothesis (TWH) predicts that females with more resources should bias their maternal investment toward offspring of the sex that is most likely to benefit from those additional resources. This paper examines the sex allocation of 61 female mountain gorillas (Gorilla beringei beringei) of the Virunga volcanoes, Rwanda from 1967 to 2004. Like most highly dimorphic, polygynous mammals, mountain gorillas are expected to show greater variance in reproductive success among males than females, so mothers in good condition should bias their investment toward sons. Using dominance rank as the indicator of maternal condition, the TWH was tentatively supported by our results with interbirth intervals (IBI). Dominant mothers had longer IBI following the birth of sons, relative to the longer IBI that subordinate mothers had with daughters. In contrast, maternal condition did not have a significant effect on birth sex ratios. We also found no significant relationships with other variables that might influence birth sex ratios (e.g., maternal age, parity, or group size), and the overall birth sex ratio was not significantly different from a 50:50 split. Collectively, our results suggest that female mountain gorillas do not control the sex ratio of their offspring at birth, but they may adjust their subsequent maternal investment. This conclusion is consistent with recurring questions about whether any adjustments in birth sex ratios occur in primates.     

The Weaker Sex? The Propensity for Male-Biased Piglet Mortality

For the most part solutions to farm animal welfare issues, such as piglet mortality, are likely to lie within the scientific disciplines of environmental design and genetic selection, however understanding the ecological basis of some of the complex dynamics observed between parent and offspring could make a valuable contribution. One interesting, and often discussed, aspect of mortality is the propensity for it to be sex-biased. This study investigated whether known physiological and behavioural indicators of piglet survival differed between the sexes and whether life history strategies (often reported in wild or feral populations) relating to parental investment were being displayed in a domestic population of pigs. Sex ratio (proportion of males (males/males+females)) at birth was 0.54 and sex allocation (maternal investment measured as piglet birth weight/litter weight) was statistically significantly male-biased at 0.55 (t₃₅ = 2.51 P = 0.017), suggesting that sows invested more in sons than daughters during gestation. Despite this investment in birth weight, a known survival indicator, total pre-weaning male mortality was statistically significantly higher than female mortality (12% vs. 7% respectively z = 2.06 P = 0.040). Males tended to suffer from crushing by the sow more than females and statistically significantly more males died from disease-related causes. Although males were born on average heavier, with higher body mass index and ponderal index, these differences were not sustained. In addition male piglets showed impaired thermoregulation compared to females. These results suggest male-biased mortality exists despite greater initial maternal investment, and therefore reflects the greater susceptibility of this sex to causal mortality factors. Life history strategies are being displayed by a domestic population of pigs with sows in this study displaying a form of parental optimism by allocating greater resources at birth to males and providing an over-supply of this more vulnerable sex in expectation of sex-biased mortality.     

The effect of maternal and fetal corticosteroids on the development of function of the pituitary-adrenocortical system.

The pituitary-adrenocortical system of rat fetuses was stimulated (larger adrenals at birth) by maternal adrenalectomy, or suppressed (smaller adrenals at birth) by implantation of an ACTH secreting pituitary tumor (MtTF4). Offspring were delivered by caesarean section and fostered to untreated females. Offspring of intact females delivered by caesarean section and normally delivered offspring of intact mothers both fostered to untreated lactating females served as controls. Body growth in the first three weeks of life was delayed in offspring of tumor bearing mothers in Control-fostered subjects as compared to the 2 other groups. At 70 days of age female offspring of the tumor implanted and adrenalectomized mothers, as well as the Control-caesarean females, had smaller adrenals than Control-fostered animals of the same sex. The adrenal size of males was not significantly affected. No significant differences were found in resting concentrations of corticosterone in plasma, although offspring of adrenalectomized mothers had high values. Suppressed adrenal response to ether stress was found in offspring of tumor bearing mothers. The supposition is that interference with maternal pituitary-adrenocortical activity during pregnancy has a long lasting effect on fetal hypothalamo-pituitary-adrenocortical system.     

Humans at tropical latitudes produce more females

Skews in the human sex ratio at birth have captivated scientists for over a century. The accepted average human natal sex ratio is slightly male biased, at 106 males per 100 females or 51.5 per cent males. Studies conducted on a localized scale show that sex ratios deviate from this average in response to a staggering number of social, economical and physiological variables. However, these patterns often prove inconsistent when expanded to other human populations, perhaps because the nature of the influences themselves exhibit substantial cultural variation. Here, data collected from 202 countries over a decade show that latitude is a primary factor influencing the ratio of males and females produced at birth; countries at tropical latitudes produced significantly fewer boys (51.1% males) annually than those at temperate and subarctic latitudes (51.3%). This pattern remained strong despite enormous continental variation in lifestyle and socio-economic status, suggesting that latitudinal variables may act as overarching cues on which sex ratio variation in humans is based.     

Red howler monkey birth data II: Interannual,habitat, and sex comparisons

Data presented in this paper are derived from the births and subsequent histories of red howler infants born in two habitats. Overall the sex ratio of infants at birth was about 1:1. Infant survivorship (at 1 yr) was about 80%, and 44% of infant mortality was attributed to infanticide by males. Survivorship curves indicated a dramatic sex difference, with far fewer females than males known to be alive at age 7 yr. However, this sex difference may be inflated because emigrant males are more easily identified than emigrant females, and females may be dispersing beyond the boundaries of the study area at a higher rate. Annual birthrate varied somewhat from year to year and was positively related to rainfall. Annual birthrate tended to be higher in the habitat with lower density and higher growth rate. Consistent with the trends, in annual birthrate, variation in interbirth interval length (TBR after births of surviving infants was related primarily to habitat differences and annual variation in rainfall. Season of birth and maternal age class had no effect on IBI. Infant sex had mostly nonsignificant effects on IBI. A small sample indicated that IBI's were significantly longer after the births of females who eventually became natal breeders than after the births of females who eventually emigrated. This difference might reflect differential parental (maternal) investment of some sort.     

Sex ratio bias in the dung beetle <Emphasis Type="Italic">Onthophagus taurus</Emphasis>: adaptive allocation or sex-specific offspring mortality?

Sex allocation theory predicts that females should adjust the sex of their offspring when the fitness returns of one sex are higher than the other. However, biased sex ratios may also arise if mortality differs between the sexes. Here, we examine whether offspring sex ratio bias in the dung beetle, Onthophagus taurus, represents adaptive sex allocation by females or is due to sex-specific mortality. First, we re-analyze an existing data set to show that females produce an excess of daughters when mating to smaller, less attractive males and near equal sex ratio with large, more attractive males. We show, that this results from females adjusting larval provisions after mating to males of variable attractiveness which in turn influences the likelihood that sons die during development. Second, we conduct a manipulative experiment varying the quantity and quality of larval provisions and show that the mortality of sons increased when larval provisions were reduced. Collectively, our work demonstrates that offspring mortality is contingent on the amount of resources provisioned by females and that sons have greater nutritional demands than daughters during development, leading to higher mortality. Our results therefore demonstrate the importance of considering sex-specific offspring mortality in studies of sex ratio evolution.     

Effects of social stress during early pregnancy on litter size and sex ratio in the golden hamster (Mesocricetus auratus)

Primiparous female hamsters were mated to proven breeders and stressed during early pregnancy. Females were housed singly throughout gestation except for Days 4, 5 and 6 when they were paired for 10-min intervals 3 times each day with another female matched for age, weight and day of pregnancy. Within each of the pairs, one female was consistently dominant to the other. Controls were exposed to a novel area instead of a conspecific. At parturition, all pups were counted, sexed and weighed. There were no significant differences between litter sizes or sex ratios (defined as % male) of control and dominant females. Litter sizes produced by control or dominant dams were significantly larger than those of subordinate dams, and litter sex ratios of dominants were significantly higher than those of subordinates. Subordinate dams produced fewer males than did dominant dams, but there was no difference in the number of females produced. Also, subordinate dams produced smaller pups than control dams. Examination of uterine implantation sites and fetal resorptions indicated that fetal loss occurred between Days 5 and 10 of pregnancy. These results suggest that subordinate dams produce smaller litters via selective resorption or spontaneous abortion of males in utero and that those males they do produce are smaller than those produced by dominant or control dams. We suggest that males are more susceptible in utero to effects of maternal stress in this species, and may require more maternal investment to survive to term.     

The optimal sex ratio for age-structured populations

A new nonlinear age-dependent model for age-structured sexual populations is introduced, based on two assumptions: (1) the birth function depends on the ages of the two parents; and (2) the death functions of the two sexes are composed of two types of additive terms depending on age and sex and on time evolution of population densities, respectively. Formal arguments are given that suggest that time-persistent age profiles may exist and that the intrinsic rate of growth for the two sexes is the same. If the ratio between the number of newborn females and the number of newborn males is equal to the square root of the ratio of the corresponding per capita birth rates, then the intrinsic rate of growth has an optimal value. The optimal sex ratio for the whole population is equal to the reciprocal value of the sex ratio at birth.     

Determinants of the sex ratio at birth: review of recent literature

The fact that more boys are born than girls (104-107 boys for every 100 girls) has been known since 1662. Factors determining the sex ratio at birth rate are of 2 kinds: factors determining the primary sex ratio, i.e., sex ratio at conception, and factors determining the survival of the embryo in utero. Y-bearing and X-bearing sperm may have different motility or different survival time. The age of the ovum at fertilization and the chemical balance of the female genital tract have an effect on sex ratio at conception. High levels of circulating gonadotropins may imply a lower sex ratio at birth as well as a higher rate of dizygotic twinning. Male conception also appears to be higher early and late in the menstrual cycle. The fact that women exposed to higher coital rates conceive earlier in the menstrual cycle may account for the greater number of boys born during wars. Prenatal male mortality is reportedly highest between gestational months 3-5, lower between months 6-8, and higher again st term. Also, immunological interaction between mother and embryo may account for some sex selective spontaneous abortions. 3 sociodemographic determinants of sex ratio at birth are thought to be maternal age, paternal age, and birth order. Higher prenatal male mortality may be correlated with socioeconomic conditions, since higher socioeconomic status lowers prenatal mortality in general. The effects of parental age, birth order, and parity are less clear. Race is also a factor, since the sex ratio at birth for blacks is lower (102-104) than for whites (106). 14 univariate and 19 multivariate studies of effects of maternal age, paternal age, parity, birth order, race, and socioeconomic status on sex ratio at birth, with sample sizes in the millions from various countries have been analyzed. More boys are born to younger parents, and lower order births have a higher proportion of males than do higher order births. In the multivariate analyses, when the effects of paternal and and birth order are controlled for, the effect of maternal age weakens, and the effect of paternal age appears to be stronger. The effect of birth order remains but is very small, and the effect of race persists independent of any effect of other variables. Maternal age, parity, and birth order are positively correlated with proportion of male stillbirths. The results of the multivariate analyses show all of the effects to be very small, but that maternal age has no effect on sex ratio at birth; paternal age and birth order have a negative effect, and the racial effect persists independent of any other effect. The racial effect is clearly biologically determined at conception because blacks have higher levels of circulating gonadotropin and therefore a higher probability of conceiving girls. Parents in higher socioeconomic classes are more likely to have sons, but the effect is largely due to the excess male mortality during most of the gestational period.     

Does fetal sex affect pregnancy outcome?

Background: In maternal fetal medicine, gender differences in outcome are often observed.Objective: This article reviews the fetal sex-dependent differences found in many aspects of pregnancy, from conception through birth.Methods: The MEDLINE, EMBASE, and Current Contents databases were searched, for the years 1985 to 2006, using the following Medical Subject Headings and text words: fetal gender, finale, female, sex ratio at birth, pregnancy outcome, preterm birth, and stillbirth. The search was not limited by language. In addition, the bibliographies of known relevant articles were examined to capture any reports not already identified in the electronic search. All reports that provided information on gender differences in pregnancy outcome were included for review.Results: An extremely high male-to-female ratio was found in fetuses born after very short-duration pregnancy; this level declined around the 20th week and stabilized at term. In the absence of manipulation, both the sex ratio at birth and the population sex ratio have been found to remain consistent. A higher incidence of preterm birth and premature preterm rupture of membranes has been observed in different populations among mothers of male newborns compared with mothers of females. It has been speculated that this higher incidence may be linked to the relatively greater weight at lower gestational age of male newborns versus females. Women carrying male fetuses had higher rates of gestational diabetes mellitus, fetal macrosomia, failure to progress during the first and second stages of labor, cord prolapse, nuchal cord, and true umbilical cord knots. Cesarean sections were also more frequently found among male neonates compared with females.Conclusions: Male sex is an independent risk factor for adverse pregnancy outcome. Evidence suggests that females have an advantage over males, with a better outcome in the perinatal period, particularly after preterm birth.Key words: fetal gender, male, female, sex ratio of birth, perinatal outcome.     

Patterns and mechanisms of sex ratio distortion in the Collaborative Cross mouse mapping population

In species with single-locus, chromosome-based mechanisms of sex determination, the laws of segregation predict an equal ratio of females to males at birth. Here, we show that departures from this Mendelian expectation are commonplace in the 8-way recombinant inbred Collaborative Cross (CC) mouse population. More than one-third of CC strains exhibit significant sex ratio distortion (SRD) at wean, with twice as many male-biased than female-biased strains. We show that these pervasive sex biases persist across multiple breeding environments, are stable over time, and are not mediated by random maternal effects. SRD exhibits a heritable component, but QTL mapping analyses fail to nominate any large effect loci. These findings, combined with the reported absence of sex ratio biases in the CC founder strains, suggest that SRD manifests from multilocus combinations of alleles only uncovered in recombined CC genomes. We explore several potential complex genetic mechanisms for SRD, including allelic interactions leading to sex-biased lethality, genetic sex reversal, chromosome drive mediated by sex-linked selfish elements, and incompatibilities between specific maternal and paternal genotypes. We show that no one mechanism offers a singular explanation for this population-wide SRD. Instead, our data present preliminary evidence for the action of distinct mechanisms of SRD at play in different strains. Taken together, our work exposes the pervasiveness of SRD in the CC population and nominates the CC as a powerful resource for investigating diverse genetic causes of biased sex chromosome transmission.     

Food restricting young hamsters (Mesocricetus auratus) affects sex ratio and growth of subsequent offspring

Trivers and Willard (1973) predicted that stressed adult female mammals may enhance their fitness by skewing offspring sex ratios and maternal investment to favor daughters. The present study investigated whether stressing young hamsters might also influence sex ratio and growth of subsequent offspring. Control females received food ad libitum (A) on Days 1-50 postpartum (AA). Experimental females were food-restricted (R) either on Days 1-25 (RA), Days 26-50 (AR), or Days 1-50 (RR) postpartum. Subjects were mated when 91-95 days old. Litter sizes and survivorship (= % litters within a treatment that contained at least one pup), sex ratio (= % males), and pup weights in the next generation were recorded every fifth day from parturition until Day 25 postpartum. Control litters contained significantly more offspring at birth than did RR litters. Sex ratio was significantly higher at birth for AA litters than for the other treatments. Postpartum sex ratio within each group remained similar to that recorded at birth. RR litters contained significantly fewer pups compared to the other three treatments from Days 5-25. RR female pups weighed significantly more at birth than their counterparts in the other treatments. Weights of males at birth were similar in all treatments. By Day 25, both male and female RR pups weighed significantly less than control, AR, and RA pups. Food restriction early in life may have long-term consequences on sex ratio and pup growth in golden hamsters.     

Litter sex ratios in Richardson’s ground squirrels: long-term data support random sex allocation and homeostasis

When costs of producing male versus female offspring differ, parents may vary allocation of resources between sons and daughters. We tested leading sex-allocation theories using an information-theoretic approach and Bayesian hierarchical models to analyse litter sex ratios (proportion males) at weaning for 1,049 litters over 24 years from a population of Richardson’s ground squirrels (Urocitellus richardsonii), a polygynandrous, annually reproducing mammal in which litter size averages from six to seven offspring and sons are significantly heavier than daughters at birth and weaning. The model representing random Mendelian sex-chromosome assortment fit the data best; a homeostatic model received similar support but other models performed poorly. Embryo resorption was rare, and 5 years of litter data in a second population revealed no differences in litter size or litter sex ratio between birth and weaning, suggesting that litter size and sex ratio are determined in early pregnancy. Sex ratio did not vary with litter size at weaning in any of 29 years, and the observed distribution of sex ratios did not differ significantly from the binomial distribution for any litter size. For 1,580 weaned litters in the two populations, average sex ratio deviated from parity in only 3 of 29 years. Heavier females made a greater reproductive investment than lighter females, weaning larger and heavier litters composed of smaller sons and daughters, but litter sex ratio was positively related to maternal mass in only 2 of 29 years. Such occasional significant patterns emphasize the importance of multi-season studies in distinguishing infrequent events from normal patterns.     

Is There Adaptive Value to Reproductive Termination in Japanese Macaques? A Test of Maternal Investment Hypotheses

Evolutionary biologists often argue that menopause evolved in the human female as the result of selection for a postreproductive phase of life, during which increased maternal investment in existing progeny could lead to enhanced survivorship of descendents. Adaptive theories relating menopause to enhanced maternal investment are known as the mother (first-generation) and grandmother (second-generation-offspring) hypotheses. Although menopause—universal midlife termination of reproduction—has not been documented in primates other than humans, some researchers have argued that postreproductive alloprimates also have a positive impact on the survivorship of first and second generation progeny. We tested the maternal investment hypotheses in Japanese macaques by comparing the survivorship of offspring, final infants, and great-offspring of females that terminated reproduction before death with females that continued to reproduce until death. SURVIVAL analyses revealed no significant difference in the survivorship of descendents of postreproductive and reproductive females, though final infants of postreproductive females were 13% more likely to survive than final infants of females that reproduced until death were. We also explored possible differences between these two groups of females, other than survivorship of progeny. We found no difference in dominance rank, matrilineal affiliation, body weight, infant sex ratio, age at first birth, fecundity rate or lifetime reproductive success. However, postreproductive females are significantly longer-lived than reproductive females and as a result experienced more years of reproduction and produced more infants in total. Apart from final infants, offspring survival is marginally lower in postreproductive females. Since offspring survival is not significantly enhanced in postreproductive females, the greater number of infants produced did not translate into greater lifetime reproductive success. Our findings fail to support the maternal investment hypotheses and instead suggest that reproductive termination in this population of Japanese macaques is most closely associated with enhanced longevity and its repercussions.     

Sex differences in mortality of Japanese macaques: Twenty-one years of data from the Arashiyama West population

Theorists argue that mortality in male mammals should be higher than that of females, and many studies of primates followed across the life course have found this to be the case. This study examines mortality patterns in the rapidly expanding Arashiyama West (Texas) population of Japanese macaques (Macaca fuscata) and finds that males have a significantly lower median survival age (12.2 years) in comparison to females (20.5 years). Males and females are born in equal proportions, but by adulthood there are 2–5 females to every male. Males are at higher risk of falling victim to infectious diseases and human-related causes of death, and they are more likely to “disappear” from the population, which is inferred to result largely from emigration. There are no significant sex differences in the risks of dying from predation, non-infectious illnesses, neonatal defect, or social stress. Males become more susceptible to mortality than females once they reach sexual maturity, and they remain at greater risk than females until their old age. There is no evidence that one sex or the other is at greater risk of dying as infants, or as juveniles. Comparing males of different age classes, adolescent and adult males are more likely to die and to disappear than are juvenile males. These findings support the “high-risk, high-gain” hypothesis that males are mainly lost to the population because of their risk-taking behaviors after sexual maturity, rather than the “fragile male” hypothesis that males are more vulnerable to mortality during the period of growth and development. Am J Phys Anthropol 102:161–175, 1997 © 1997 Wiley-Liss, Inc.     

Host parasitoid interactions affecting reproduction and oviposition byBrachymeria intermedia [Hym.: Chalcididae]

A maximum number of 6 parasitoid progeny are produced byBrachymeria intermedia (Nees) females, in a 24 h period, even when more than 6 hosts are available. The number of progeny produced by ovipositing females kept at a high temperature or high light intensity is greater than that of females kept at low temperatures or low light intensity. Host size and age of female parasitoids affect the sex ratio or progeny. Parasitism of small pupal hosts results in the production of a greater proportion of male progeny. Increasing maternal age appears to increase the proportion of males.     

Equal investment in male and female offspring in southern elephant seals

Sex ratio theory predictions concerning differential parental investment in offspring by sex were tested on southern elephant seals, Mirounga leonina , breeding at Península Valdés, Argentina. Females invested equally in sons and daughters, as reflected by the similar mass at birth (mean ± 1 S.D.) of 14 males (44.1 ± 6.5 kg) and 14 females (43.4 ± 3.8 kg), and similar mass at weaning of 52 males (131.5 ± 22.4 kg) and 38 females (131.4 ± 18.3 kg). There were also no sex differences in the rate of mass gain during nursing (males = 4.0 ± 0.9 kg/day; females = 3.9 ± 0.8 kg/day), rate of mass loss during the first month of post-weaning fast (males = 0.85 ± 0.19 kg/day; females = 0.92 ± 0.15 kg/day), mean age at weaning (males = 22.3 ± 1.6 days; females = 22.7 ± 1.7 days), and female nursing behaviour. Mother's size accounted for most of the variation in mass of pups at weaning. Mothers ranked as small, medium and large, weaned pups with a mean mass of 102, 130 and 145 kg, respectively. The sex ratio of weanlings did not differ from unity. These data are consistent with Fisher's (1930) sex ratio theory.