Does multiple paternity influence offspring disease resistance?

It has been suggested that polyandry allows females to increase offspring genetic diversity and reduce the prevalence and susceptibility of their offspring to infectious diseases. We tested this hypothesis in wild‐derived house mice (Mus musculus) by experimentally infecting the offspring from 15 single‐ and 15 multiple‐sired litters with two different strains of a mouse pathogen (Salmonella Typhimurium) and compared their ability to control infection. We found a high variation in individual infection resistance (measured with pathogen loads) and significant differences among families, suggesting genetic effects on Salmonella resistance, but we found no difference in prevalence or infection resistance between single‐ vs. multiple‐sired litters. We found a significant sex difference in infection resistance, but surprisingly, males were more resistant to infection than females. Also, infection resistance was correlated with weight loss during infection, although only for females, indicating that susceptibility to infection had more harmful health consequences for females than for males. To our knowledge, our findings provide the first evidence for sex‐dependent resistance to Salmonella infection in house mice. Our results do not support the hypothesis that multiple‐sired litters are more likely to survive infection than single‐sired litters; however, as we explain, additional studies are required before ruling out this hypothesis.     

Change in offspring sex ratio over a very short season in Lincoln's Sparrows: the potential role of bill development

ABSTRACT The sex ratios of offspring are targets of natural selection that can affect parental energy expenditure and fitness, adult sex ratios, and population dynamics. Parents may manipulate offspring sex ratios based on sex differences in their offsprings' potential for reproductive success. In Lincoln's Sparrows (Melospiza lincolnii), male bill shape is associated with the quality of songs, and song quality predicts female preferences in a reproductive context. Males and females that hatch later relative to brood mates or later in the breeding season tend to develop bill shapes that are, for males, associated with low‐quality song. Because females do not sing and do not experience this selection pressure, we predicted that the sex of offspring produced late relative to their brood mates or relative to the season should be biased toward females. Using a molecular technique to sex nestlings, we found no effects of hatching order or any interaction between date of clutch initiation (season) and hatching order on offspring sex. However, we found a seasonal decline in the proportion of male offspring, from approximately 0.8 at the beginning to 0.4 at the end of a clutch initiation season only 19 d in duration. To our knowledge, this is the shortest period over which the offspring sex ratio has been shown to change in a bird population. Moreover, these findings are consistent with the hypothesis that sex differences in the potential attractiveness of offspring ultimately influence offspring sex ratios.     

Male-biased parasitism by common helminths is not explained by sex differences in body size or spleen mass of breeding cormorants Phalacrocorax auritus

In vertebrates, males are often more parasitised than conspecific females. This bias in parasitism might result from sex differences in parasite exposure and/or susceptibility to infection. Such information is important for testing hypotheses about allocation of resources to life histories of males and females and for testing hypotheses about factors thought to influence parasite fitness and parasite dynamics. We tested whether double-crested cormorants Phalacrocorax auritus exhibit male-biased parasitism by gut helminths. The prevalence of nematode Contracaecum spp. and trematode Drepanocaphalus spathans infections was ∼90% and 39%, respectively. Cestode, primarily Paradilepis caballeroi and acanthocephalan Andracantha gravida infections were less common (<10%). Male and female cormorants did not differ in prevalence of infection by any helminth species. However, males had twice the abundance and intensity of Contracaecum spp. infections and twice the intensity of D. spathans infections than found in females. For common parasites showing male-biased parasitism, degree of parasitism was also unrelated to body size or mass in either sex. Males and females did not differ in spleen mass and spleen mass was unrelated to abundance of common parasites. Furthermore, abundance of trematodes and nematodes was not correlated. At present, male biases in parasitism by nematodes and trematodes in cormorants are independent patterns that remain unexplained, but are most likely attributable to sex differences in exposure and/or immunological differences not yet assessed.     

The evolution of sex-specific immune defences

Why do males and females often differ in their ability to cope with infection? Beyond physiological mechanisms, it has recently been proposed that life-history theory could explain immune differences from an adaptive point of view in relation to sex-specific reproductive strategies. However, a point often overlooked is that the benefits of immunity, and possibly the costs, depend not only on the host genotype but also on the presence and the phenotype of pathogens. To address this issue we developed an adaptive dynamic model that includes host–pathogen population dynamics and host sexual reproduction. Our model predicts that, although different reproductive strategies, following Bateman''s principle, are not enough to select for different levels of immunity, males and females respond differently to further changes in the characteristics of either sex. For example, if males are more exposed to infection than females (e.g. for behavioural reasons), it is possible to see them evolve lower immunocompetence than females. This and other counterintuitive results highlight the importance of ecological feedbacks in the evolution of immune defences. While this study focuses on sex-specific natural selection, it could easily be extended to include sexual selection and thus help to understand the interplay between the two processes.     

Sex‐specific aging in animals: Perspective and future directions

Sex differences in aging occur in many animal species, and they include sex differences in lifespan, in the onset and progression of age‐associated decline, and in physiological and molecular markers of aging. Sex differences in aging vary greatly across the animal kingdom. For example, there are species with longer‐lived females, species where males live longer, and species lacking sex differences in lifespan. The underlying causes of sex differences in aging remain mostly unknown. Currently, we do not understand the molecular drivers of sex differences in aging, or whether they are related to the accepted hallmarks or pillars of aging or linked to other well‐characterized processes. In particular, understanding the role of sex‐determination mechanisms and sex differences in aging is relatively understudied. Here, we take a comparative, interdisciplinary approach to explore various hypotheses about how sex differences in aging arise. We discuss genomic, morphological, and environmental differences between the sexes and how these relate to sex differences in aging. Finally, we present some suggestions for future research in this area and provide recommendations for promising experimental designs.     

Sex-specific immunization for sexually transmitted infections such as human papillomavirus: insights from mathematical models

Background

Sex-specific differences regarding the transmissibility and the course of infection are the rule rather than the exception in the epidemiology of sexually transmitted infections (STIs). Human papillomavirus (HPV) provides an example: disease outcomes differ between men and women, as does the potential for transmission to the opposite sex. HPV vaccination of preadolescent girls was recently introduced in many countries, and inclusion of boys in the vaccination programs is being discussed. Here, we address the question of whether vaccinating females only, males only, or both sexes is the most effective strategy to reduce the population prevalence of an STI like HPV.

Methods and Findings

We use a range of two-sex transmission models with varying detail to identify general criteria for allocating a prophylactic vaccine between both sexes. The most effective reduction in the population prevalence of infection is always achieved by single-sex vaccination; vaccinating the sex with the highest prevaccine prevalence is the preferred strategy in most circumstances. Exceptions arise only when the higher prevaccine prevalence is due to a substantially lower rate of natural immunity, or when natural immunity is lifelong, and a prolonged duration of infectiousness coincides with increased transmissibility. Predictions from simple models were confirmed in simulations based on an elaborate HPV transmission model. Our analysis suggests that relatively inefficient genital transmission from males to females might render male vaccination more effective in reducing overall infection levels. However, most existing HPV vaccination programs have achieved sufficient coverage to continue with female-only vaccination.

Conclusions

Increasing vaccine uptake among preadolescent girls is more effective in reducing HPV infection than including boys in existing vaccination programs. As a rule, directing prophylactic immunization at the sex with the highest prevaccine prevalence results in the largest reduction of the population prevalence. Please see later in the article for the Editors'' Summary     

Indices to Measure Risk of HIV Acquisition in Rakai,Uganda

Introduction

Targeting most-at-risk individuals with HIV preventive interventions is cost-effective. We developed gender-specific indices to measure risk of HIV among sexually active individuals in Rakai, Uganda.

Methods

We used multivariable Cox proportional hazards models to estimate time-to-HIV infection associated with candidate predictors. Reduced models were determined using backward selection procedures with Akaike''s information criterion (AIC) as the stopping rule. Model discrimination was determined using Harrell''s concordance index (c index). Model calibration was determined graphically. Nomograms were used to present the final prediction models.

Results

We used samples of 7,497 women and 5,783 men. 342 new infections occurred among females (incidence 1.11/100 person years,) and 225 among the males (incidence 1.00/100 person years). The final model for men included age, education, circumcision status, number of sexual partners, genital ulcer disease symptoms, alcohol use before sex, partner in high risk employment, community type, being unaware of a partner''s HIV status and community HIV prevalence. The Model''s optimism-corrected c index was 69.1 percent (95% CI = 0.66, 0.73). The final women''s model included age, marital status, education, number of sex partners, new sex partner, alcohol consumption by self or partner before sex, concurrent sexual partners, being employed in a high-risk occupation, having genital ulcer disease symptoms, community HIV prevalence, and perceiving oneself or partner to be exposed to HIV. The models optimism-corrected c index was 0.67 (95% CI = 0.64, 0.70). Both models were well calibrated.

Conclusion

These indices were discriminative and well calibrated. This provides proof-of-concept that population-based HIV risk indices can be developed. Further research to validate these indices for other populations is needed.     

Prevalence and intensity of avian malaria in a quail hybrid zone

Hybrid zones have been described as natural laboratories by researchers who study speciation and the various mechanisms that may affect gene flow. The evolutionary consequences of hybridization depend not only on reproductive compatibility between sympatric species, but also on factors like vulnerability to each other''s predators and parasites. We examined infection patterns of the blood parasite Haemoproteus lophortyx, a causative agent of avian malaria, at a site in the contact zone between California quail (Callipepla californica) and Gambel''s quail (C. gambelii). Controlling for the potential influence of sex and year, we tested whether species identity predicted infection status and intensity. We found that infection prevalence was lower in California and hybrid quail compared with Gambel''s quail. However, infected California and hybrid quail had higher infection intensities than Gambel''s quail. California and hybrid quail exhibited no significant differences in prevalence or intensity of infection. These findings suggest that infection by H. lophortyx has the potential to influence species barrier dynamics in this system; however, more work is necessary to determine the exact evolutionary consequences of this blood parasite on hybridization.     

Host sexual dimorphism and parasite adaptation

In species with separate sexes, parasite prevalence and disease expression is often different between males and females. This effect has mainly been attributed to sex differences in host traits, such as immune response. Here, we make the case for how properties of the parasites themselves can also matter. Specifically, we suggest that differences between host sexes in many different traits, such as morphology and hormone levels, can impose selection on parasites. This selection can eventually lead to parasite adaptations specific to the host sex more commonly encountered, or to differential expression of parasite traits depending on which host sex they find themselves in. Parasites adapted to the sex of the host in this way can contribute to differences between males and females in disease prevalence and expression. Considering those possibilities can help shed light on host-parasite interactions, and impact epidemiological and medical science.     

High incidence of the maternally inherited bacterium Cardinium in spiders

Inherited bacteria are now recognized as important players in arthropod evolution and ecology. Here, we test spiders, a group recently identified as possessing inherited bacteria commonly, for the presence of two reproductive parasites, Cardinium hertigii (Bacteroidetes group) and Wolbachia (α-proteobacteria), estimating incidence, prevalence, any sex bias in infection, and infection diversity, for a panel of field-collected specimens. We identify spiders as a hotspot for Cardinium . Present in 22% of the sampled species, incidence was significantly higher than that previously recorded in insects. Where present, Cardinium infection occurred at medium prevalence without evidence of sex bias in prevalence that would indicate sex-ratio distortion activity. Wolbachia was present in 37% of species, but revealed a gradation from being rare to very common. In one case, Wolbachia was found significantly more commonly in females than males, indicating it may act as a sex-ratio distorter in some species. Breeding work conducted on two species confirmed that Wolbachia and Cardinium were transmitted maternally, which represents the first proof of inheritance of these symbionts in spiders. Overall, this study demonstrates that the majority of spider species are infected with inherited bacteria, and their role in host biology clearly requires determination.     

Both sexes suffer increased parasitism and reduced energy storage as costs of reproduction in the brown anole,Anolis sagrei

Sexual selection theory proposes that males suffer reduced immune function and increased parasitism as costs of expressing sexual signals. Life‐history theory proposes that females suffer the same costs because of inherent trade‐offs between reproduction and self‐maintenance. Mechanistically, each theory invokes an energetic trade‐off, although few experiments have directly compared these costs of reproduction between the sexes as a result of fundamental sex differences in the nature of reproductive investment and a tendency for each theory to focus on a single sex. To test whether males and females experience comparable costs of reproduction in terms of energetics, immune function, and parasitism, we used gonadectomy to eliminate most aspects of reproductive investment in wild brown anole lizards (Anolis sagrei) of both sexes. We compared these nonreproductive males and females with intact, reproductive controls with respect to stored energy (fat bodies), immune function (swelling response to phytohemagglutinin), and the prevalence and intensity of infection by four types of parasite (gastric nematodes, intestinal nematodes, faecal coccidia, and ectoparasitic mites). Gonadectomized anoles experienced dramatic increases in fat storage that were accompanied by decreases in the prevalence of intestinal nematodes and in the intensity of coccidia infection. These costs of reproduction were comparable between males and females, although neither sex exhibited the predicted increase in immune function after gonadectomy. Our results suggest that, despite fundamental sex differences in the nature of reproductive investment, both male and female anoles experience similar costs of reproduction with respect to energy storage and some aspects of parasitism.     

Apparently-Different Clearance Rates from Cohort Studies of Mycoplasma genitalium Are Consistent after Accounting for Incidence of Infection,Recurrent Infection,and Study Design

Mycoplasma genitalium is a potentially major cause of urethritis, cervicitis, pelvic inflammatory disease, infertility, and increased HIV risk. A better understanding of its natural history is crucial to informing control policy. Two extensive cohort studies (students in London, UK; Ugandan sex workers) suggest very different clearance rates; we aimed to understand the reasons and obtain improved estimates by making maximal use of the data from the studies. As M. genitalium is a sexually-transmitted infectious disease, we developed a model for time-to-event analysis that incorporates the processes of (re)infection and clearance, and fitted to data from the two cohort studies to estimate incidence and clearance rates under different scenarios of sexual partnership dynamics and study design (including sample handling and associated test sensitivity). In the London students, the estimated clearance rate is 0.80p.a. (mean duration 15 months), with incidence 1.31%-3.93%p.a. Without adjusting for study design, corresponding estimates from the Ugandan data are 3.44p.a. (mean duration 3.5 months) and 58%p.a. Apparent differences in clearance rates are probably mostly due to lower testing sensitivity in the Uganda study due to differences in sample handling, with ''true'' clearance rates being similar, and adjusted incidence in Uganda being 28%p.a. Some differences are perhaps due to the sex workers having more-frequent antibiotic treatment, whilst reinfection within ongoing sexual partnerships might have caused some of the apparently-persistent infection in the London students. More information on partnership dynamics would inform more accurate estimates of natural-history parameters. Detailed studies in men are also required.     

Sex differences in disease avoidance behavior vary across modes of pathogen exposure

Sex differences in disease susceptibility are widespread, and these disparities are often compounded in cases where sexual dimorphism increases exposure risk to parasites for one sex more than the other. Studies rarely link sex differences in disease susceptibility to sex differences in infection avoidance behavior. Yet, understanding the intersection of hosts’ susceptibility to infection and infection avoidance behavior is essential to predicting infection risk variation. Here, we use the fruit fly Drosophila melanogaster and a generalist entomopathogenic fungus, Metarhizium robertsii, which can be transmitted directly, indirectly, and post-mortem as a model host–pathogen system. We test whether the relationship between susceptibility to infection and pathogen avoidance behavior covaries with host sex. We first measured differences in resistance between male and female flies after three different types of exposure—direct, sexual, and environmental—to infectious fungal conidiospores. Then, we tested whether male and female flies differed in the likelihood of mating with infected partners and their avoidance of food patches with increased infection risk. Females were more susceptible to infection under all three exposure techniques. When confronted with an infectious partner, females mated sooner than males. However, when given a choice between an exposed partner and an unexposed partner, females take longer to begin copulating compared with males, though neither sex was more likely to choose the unexposed partner than expected by chance. Neither male nor females flies avoided food patches containing infectious conidiospores, though only females show an aversion to food sites containing an infectious fly corpse. These experiments suggest that sex differences in disease susceptibility may be counteracted via differential pathogen avoidance behavior, though the strength of avoidance behavior appears to vary across different contexts of infection risk.     

Hand osteoarthritis in the Abkhazian population

The aim of the study was to evaluate the prevalence and pattern of radiographic hand osteoarthritis (OA) in an Abkhazian community-based sample and its association with age, sex, body mass index (BMI) and place of residence.The study sample was comprised of 542 males with a mean age of 43.9, sd 15.6 years and 463 females with a mean age of 44.9, sd 13.9 years. OA was evaluated for 14 joints of the left hand according to the Kellgren and Lawrence grading scheme. Statistical analyses included prevalence estimation, multiple regression analysis and χ² tests.In the entire Abkhazian sample the average prevalence of hand OA was 33.6% for males and 35.4% for females. After age 65, the prevalence of hand OA was 87.5% for males and 83.3% for females. No sex differences were found in the prevalence or number of affected hand joints. Statistically significant association was found between the number of affected joints and BMI, but not between the prevalence of hand OA and BMI. Different prevalences of radiographic hand OA were found in individuals from different villages, after adjustment for age, sex and BMI.Additional studies are needed to explore the possible reasons for such differences.     

Sexually dimorphic neuron addition to an avian song-control region is not accounted for by sex differences in cell death

Only male zebra finches sing, and several brain regions implicated in song behavior exhibit marked sex differences in neuron number. In one region, the high vocal center (HVC), this dimorphism develops because the incorporation of new neurons is greater in males than in females during the first several weeks after hatching. Although estrogen (E₂) exposure stimulates neuron addition in females, it is not known where (E₂) acts, or to what extent sexual differentiation influences the production, specification, or survival of HVC neurons. In the present study we first reassessed sex and (E₂)-induced differences in cell degeneration within the HVC using the TUNEL technique to identify cells undergoing DNA fragmentation indicative of apoptosis. HVC neuron number, as well as the density and number of TUNEL-labeled and pyknotic cells within the HVC were measured in normal 20- and 30-day-old males and females, and in 30-day-old females implanted with E₂ on posthatch day 18. Although HVC neuron number was greater in males than in females, and was masculinized in E₂ females, no group differences were evident in the absolute number of dying cells. These results indicate that sex differences in cell survival within the HVC do not entirely account for sexually dimorphic neuron addition to this region. Rather, sexual differentiation acts on some HVC neurons before they complete their migration and/or early differentiation. Although the migratory route of HVC neurons is not known, a large number of E₂ receptor-containing cells (ER cells) reside just ventromedial to the HVC and adjacent to the proliferative ventricular zone. Next, we investigated whether these ER cells contribute to early-arising sex differences in HVC neuron addition. By combining [³H] thymidine autoradiography with immunocytochemistry for ERs, we first established that ER-expressing cells are not generated during posthatch sexually dimorphic HVC neuron addition, and thus are not young HVC neurons that transiently express ERs during their migration. Furthermore, in 25-day-old birds we found no sex difference in the density of pyknotic cells among this group of ER cells, suggesting that these cells do not promote the differential survival of HVC neuronal precursors migrating through this region. Rather, ER cells or other cell populations may establish sex differences in HVC neuron number by creating dimorphisms in cellular specification. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 61–71, 1997     

Intestinal parasites of sympatric Pan troglodytes and Papio Spp. at two sites: Gombe (Tanzania) and Mt. Assirik (Senegal)

Experimental and clinical parasitology need natural baselines or “controls”. We present normative data intestinal parasite loads in two genera of African primates. Wild Pan troglodytes and Papio spp. were studied at two sites: Gombe in Tanzania (P. anubis) and Mt. Assirik in Senegal (P. papio). Presence or absence of parasites, especially nematodes, was recorded from fecal specimens. Gombe's primates were more often infected than were Mt. Assirik's. At Gombe, but not at Mt. Assirik, chimpanzees seemed to have a higher incidence of infection than baboons. Comparison of three baboon troops yielded apparent differences in prevalence of infection. No differences in infection were found between the wet and dry seasons in Mt. Assirik's chimpanzees.     

Mating Competition,Promiscuity, and Life History Traits as Predictors of Sexually Transmitted Disease Risk in Primates

Competition among males influences the distribution of copulations and should therefore influence the spread of sexually transmitted diseases (STDs). We developed a model to investigate STDs in the mating and social systems found in primates, and we tested predictions using comparative methods. In the model, groups were distributed on a square lattice in which males or females disperse and males undergo characteristic dominance trajectories at maturity (challenge vs. queuing). We investigated the impact of mating rate, mating skew, migration rate of males or females, and group size on disease spread and prevalence. The model generated several predictions: 1) STD prevalence is higher in females than males; 2) STD risk increases with copulation rate; 3) high skew is negatively associated with STD risk; 4) STD risk is higher for all individuals when females disperse and 5) when mortality rates are lower; and 6) reproductive skew and later age of male dominance (queuing) produce more strongly female-biased STD prevalence. In comparative tests, we quantified STD risk as prevalence and richness of sexually transmitted organisms at the host species level. We found positive associations between host longevity and higher STD richness, and only (nonsignificant) weak trends for females to have higher STD prevalence. Mating skew showed a weakly positive association with STD richness, contrary to predictions of our model but consistent with predictions from a previous model. In some tests, we also found that female dispersal resulted in greater STD infection risk. Collectively, these results demonstrate that mating competition and demography influence patterns of STD infection, with mortality rates having the strongest effects in comparative tests.     

Sex differences in the response to influenza virus infection: modulation by stress

Influenza virus infection is a significant public health problem; however factors affecting the incidence and severity of disease have not been fully elucidated. The present study sought to examine the role of sex and stress in mediating susceptibility to an influenza viral infection in mice. Male and female mice underwent repeated cycles of restraint (RST) stress, followed by an influenza A/PR8 virus infection. Following these manipulations, levels of circulating corticosterone, lung proinflammatory cytokine gene expression and sickness behavior were examined. The data indicate sex differences in several aspects of the response to the A/PR8 virus infection. The kinetics of lung interleukin-1β mRNA expression were faster in infected males compared to females, while circulating corticosterone levels were elevated in infected females, but not in males. Anorexia and reduced saccharin consumption began earlier and symptoms were more pronounced in infected males than in females. In addition, RST modulated the response to the A/PR8 virus infection. Proinflammatory cytokine gene expression in response to infection was enhanced and sickness behavior was modulated by RST in both males and females. These data suggest that males mount more vigorous immune and behavioral responses to influenza viral infection compared to females, and stress exacerbates the response in both males and females. In conclusion, complex interactions between biological and behavioral factors are involved in mediating individual differences in health and disease. Additional studies may help uncover some of the factors contributing to the individual differences in susceptibility to influenza infection.     

Gender and genetic background effects on brain metal levels in APP transgenic and normal mice: implications for Alzheimer beta-amyloid pathology

The incidence of Alzheimer's disease (AD) is greater in women than men at any age, as is the development of amyloid pathology in several transgenic mouse models of AD. Due to the involvement of metals in AD pathogenesis, variations between the sexes in metal metabolism may contribute to the sex difference in AD risk. In this study, we investigated sex differences in brain metal levels across the lifespan in mice of two different background strains, as well as in mice overexpressing the human amyloid precursor protein (APP) and amyloid-beta protein (Abeta). We demonstrate consistently lower Cu and higher Mn levels in females compared with males at any age studied. The sex differences in Cu and Mn levels are independent of APP/Abeta expression. AD brain exhibits decreased Cu and increased Mn levels, as do transgenic mice overexpressing APP or Abeta. The age-dependent elevations of Cu, Fe and Co levels were found to be significantly greater in mice of B6/SJL background compared with B6/DBA. If depleting Cu and/or rising Mn levels contribute to AD pathogenesis, natural sex differences in these brain metal levels may contribute to the increased propensity of females to develop AD.