Optimal immune specificity at the intersection of host life history and parasite epidemiology

Hosts diverge widely in how, and how well, they defend themselves against infection and immunopathology. Why are hosts so heterogeneous? Both epidemiology and life history are commonly hypothesized to influence host immune strategy, but the relationship between immune strategy and each factor has commonly been investigated in isolation. Here, we show that interactions between life history and epidemiology are crucial for determining optimal immune specificity and sensitivity. We propose a demographically-structured population dynamics model, in which we explore sensitivity and specificity of immune responses when epidemiological risks vary with age. We find that variation in life history traits associated with both reproduction and longevity alters optimal immune strategies–but the magnitude and sometimes even direction of these effects depends on how epidemiological risks vary across life. An especially compelling example that explains previously-puzzling empirical observations is that depending on whether infection risk declines or rises at reproductive maturity, later reproductive maturity can select for either greater or lower immune specificity, potentially illustrating why studies of lifespan and immune variation across taxa have been inconclusive. Thus, the sign of selection on the life history-immune specificity relationship can be reversed in different epidemiological contexts. Drawing on published life history data from a variety of chordate taxa, we generate testable predictions for this facet of the optimal immune strategy. Our results shed light on the causes of the heterogeneity found in immune defenses both within and among species and the ultimate variability of the relationship between life history and immune specificity.

Reproductive Suicide: Similar Mechanisms of Aging in C. elegans and Pacific Salmon

In some species of salmon, reproductive maturity triggers the development of massive pathology resulting from reproductive effort, leading to rapid post-reproductive death. Such reproductive death, which occurs in many semelparous organisms (with a single bout of reproduction), can be prevented by blocking reproductive maturation, and this can increase lifespan dramatically. Reproductive death is often viewed as distinct from senescence in iteroparous organisms (with multiple bouts of reproduction) such as humans. Here we review the evidence that reproductive death occurs in C. elegans and discuss what this means for its use as a model organism to study aging. Inhibiting insulin/IGF-1 signaling and germline removal suppresses reproductive death and greatly extends lifespan in C. elegans, but can also extend lifespan to a small extent in iteroparous organisms. We argue that mechanisms of senescence operative in reproductive death exist in a less catastrophic form in iteroparous organisms, particularly those that involve costly resource reallocation, and exhibit endocrine-regulated plasticity. Thus, mechanisms of senescence in semelparous organisms (including plants) and iteroparous ones form an etiological continuum. Therefore understanding mechanisms of reproductive death in C. elegans can teach us about some mechanisms of senescence that are operative in iteroparous organisms.

Early and late fawn mortality in a remnant population of Arabian gazelles (Gazella arabica)

The Arabian gazelle (Gazella arabica) population in Israel has experienced a turbulent conservation history and repeatedly faced local extinction. Low fawn survival was considered the main cause for the constant decline. In our study, we analyzed instantaneous fawn mortality rates, using a binomial coding at three different developmental stages, i.e., mortality rates to 3 months after parturition (weaning age), to 5 months after parturition (male fawns leave their mothers), and to the age of reproductive maturity, i.e., recruitment (12 months). We used a dataset obtained from 20 individually discernible mothers and their fawns (49 females and 48 males) born between June 2006 and September 2019. To explore causes for the fawn mortality rates, parental- (age of the mother at parturition) and offspring-related attributes (offspring sex), year of birth, together with one weather variable (mean monthly maximum temperature) were included as independent variables into three independent mixed effects cox regression models. Out of 97 fawns, 92 survived to weaning age, 73 to the age of 5 months and only 7 to the age of reproductive maturity. Temperature had significant effects on instantaneous fawn mortality rates, suggesting that low temperatures were detrimental to the survival of fawns after weaning (4–5 months) and male dispersal age (6–12 months). Male offspring encountered a higher instantaneous mortality rate than female offspring at the age of 6–12 months. Moreover, fawns from less experienced mother (young age at parturition) experienced higher mortality. Our results were in line with previous studies on fawn mortality observed in other desert dwelling ungulates.

Peripubertal Anti-Mullerian Hormone Levels Are Associated With Hyperandrogenemia During Adolescence: The Avon Longitudinal Study of Parents and Children

Polycystic ovary syndrome (PCOS) is among the most common endocrine disorders in women and is associated with negative reproductive and metabolic outcomes including subfertility, pregnancy complications, metabolic syndrome, and type 2 diabetes. The diagnosis of PCOS cannot be made until reproductive maturity, when the diagnostic criteria of hyperandrogenemia and oligomenorrhea develop. However, studies have described early metabolic and reproductive characteristics of the disorder in girls at increased risk, suggesting the pathogenesis starts much earlier. Indeed, studies in animal models suggest that exposure to excessive androgen or anti-Mullerian hormone (AMH) levels during critical developmental periods can program the offspring to develop the metabolic and reproductive features of PCOS during reproductive maturity. We investigated early maternal or peripubertal factors associated with hyperandrogenemia during adolescence using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a United Kingdom birth cohort which has been ongoing since 1991. We performed linear regression to test for an association of testosterone levels at 15 years with peripubertal reproductive and metabolic phenotypes and with maternal measures of insulin sensitivity. Peripubertal phenotypes included AMH levels at 7, 9, and 11 years, and androstenedione, DHEAS, SHBG, IGF-1, fasting insulin, QUICKI, post-glucose insulin, leptin and adiponectin at age 8 years. Maternal phenotypes included fasting insulin levels and QUICKI at a post-partum visit. Unadjusted and adjusted analyses including the covariates pubertal stage, ethnicity, maternal and daughter BMI were performed. Testosterone levels at age 15 years were significantly positively associated with AMH levels at ages 7(N=299), 9(N=295), and 11(N=300) years in both the adjusted and unadjusted models (Age 7 unadjusted P<0.0001, adjusted P=0.01; Age 9 unadjusted P<0.0001, adjusted P=0.003; Age 11 unadjusted P<0.0001, adjusted P=0.02). Testosterone at age 15 years was also associated with DHEAS at age 8 years using the unadjusted (P<0.0001) but not the adjusted model. There was no significant association between any of the other peripubertal metabolic and reproductive phenotypes or the maternal metabolic phenotypes of fasting insulin and QUICKI with testosterone level at age 15 years. We have found a persistent and significant positive association of AMH levels at pre- or peri-pubertal ages with testosterone levels during adolescence, a developmental stage at which a clinical diagnosis of PCOS can be made. It remains unclear if this early elevation in AMH contributes to the pathogenesis of hyperandrogenemia or is an early marker of PCOS. Nonetheless, these findings suggest there are early differences in the reproductive phenotype in girls with hyperandrogenemia, even before the onset of puberty.

Attainment and Maintenance of Pubertal Cyclicity May Predict Reproductive Longevity in Beef Heifers†

We hypothesized the manner that heifers achieve puberty may indicate their future reproductive longevity. Heifers with discontinued or delayed cyclicity during puberty attainment may have irregular reproductive cycles, anovulation, and infertility in their first breeding season contributing to a shorter reproductive lifespan. Therefore, plasma progesterone (P4) was measured from weaning to breeding on 611 heifers born 2012–2017 and four pubertal classifications were identified: 1) Early; P4 ≥ 1 ng/ml < March 12 with continued cyclicity, 2) Typical; P4 ≥ 1 ng/ml ≥ March 12 with continued cyclicity, 3) Start-Stop; P4 ≥ 1 ng/ml but discontinued cyclicity, and 4) Non-Cycling; no P4 ≥ 1 ng/ml. Historical herd records indicated that 25% of heifers achieved puberty prior to March 12th in the 10 years prior to the study. Start-Stop and Non-Cycling yearling heifers were lighter indicating reduced growth and reproductive maturity traits compared to Early/Typical heifers. In addition, Non-Cycling/Start-Stop heifers were less responsive to prostaglandin F2 alpha (PGF2α) to initiate estrous behavior and ovulation to be artificially inseminated. Non-Cycling heifers had fewer reproductive tract score-5 and reduced numbers of calves born in the first 21-days-of-calving during their first breeding season. Within the Start-Stop classification, 50% of heifers reinitiated cyclicity with growth traits and reproductive parameters that were similar to heifers in the Early/Typical classification while those that remained non-cyclic were more similar to heifers in the Non-Cycling group. Thus, heifers with discontinued cyclicity or no cyclicity during puberty attainment had delayed reproductive maturity resulting in subfertility and potentially a shorter reproductive lifespan.

Semelparity and Reproductive Death in Caenorhabditis elegans

In some species of salmon, reproductive maturity triggers the development of massive pathology resulting from reproductive effort, leading to rapid post-reproductive death. Such reproductive death, which occurs in many semelparous organisms (with a single bout of reproduction), can be prevented by blocking reproductive maturation, and this can increase lifespan dramatically. Reproductive death is often viewed as distinct from senescence in iteroparous organisms (with multiple bouts of reproduction) such as humans. Here we review the evidence that reproductive death occurs in C. elegans and discuss what this means for its use as a model organism to study aging. Inhibiting insulin/IGF-1 signaling and germline removal suppresses reproductive death and greatly extends lifespan in C. elegans, but can also extend lifespan to a small extent in iteroparous organisms. We argue that mechanisms of senescence operative in reproductive death exist in a less catastrophic form in iteroparous organisms, particularly those involving costly resource reallocation, and exhibiting endocrine-regulated plasticity. Thus, mechanisms of senescence in semelparous organisms (including plants) and iteroparous ones form an etiological continuum. Therefore understanding mechanisms of reproductive death in C. elegans can teach us about some mechanisms of senescence that are operative in iteroparous organisms.

Using a Multi-Century Post-Fire Chronosequence to Develop Criteria to Distinguish Prior and Bowman’s (2020) Post-Fire Obligate Coloniser and Fire-Intolerant Flora

Prior and Bowman added a new dimension to existing frameworks of post-fire responses of woody plants, by including the trait of colonisation ability (C) for those taxa which neither resprout (Rf−) nor produce seedlings (Sf−) after fire. Specifically, they recognised distinctions between: (i) post-fire obligate colonisers, being species that neither resprout nor produce seedlings from persistent seed banks post-fire but are able to colonise burnt areas through dispersal from unburnt populations, and (ii) fire-intolerant, which are unable to recover after fire by either resprouting, seeding or colonisation. We use data on temporal and spatial patterns of colonisation of Rf−Sf− mistletoes from a chronosequence study with an exceptionally long span of times since fire as a practical example of the delineation of post-fire obligate coloniser and fire-intolerant species. We propose that when a population of a species is burnt, if the species is unable to regularly colonise and reach reproductive maturity in burnt areas spatially distant from fire edges within plausible and regularly-occurring maximum fire-return intervals for the now-burnt community type, it would be classified as fire-intolerant. In our examples, Lysiana meets the criteria for fire-intolerant in obligate-seeder eucalypt woodland, while Amyema is classed as a post-fire obligate coloniser.

Age and size effects on first cone production among white spruce trees

The onset of lifetime reproduction is central to processes of plant adaptation and population changes. The relative contributions of size and age to the onset of reproduction are important to predicting that key event in individuals. To estimate respective size and age effects on first reproduction in a conifer, I observed white spruce (Picea glauca (Moench) Voss) trees in forest stands in Alaska, United States, over ranges of cumulative growth rates. Age was estimated by counting annular growth rings, size was indicated by tree height, and reproductive status was indicated by seed cones. Multiple logistic regression showed the relative contributions of tree height and age, adjusted for each other, to statistical predictions of reproductive maturity. Trees selected for having little competition for light first produced cones at heights between 1 and 5 m with little additional effect of age. Tree height contributed approximately 50% to regression predictions of reproductive maturity. In contrast, tree age contributed ≤1.5% and bore little relation to reproductive maturity other than as a component of growth rate. This is among the first reports to partial the effect sizes of tree size and age on the commencement of lifetime reproduction in a conifer.

Zinc concentrations in teeth of female walruses reflect the onset of reproductive maturity

Age at maturity is an important parameter in many demographic models and, for some species, can be difficult to obtain using traditional methods. Incremental growth structures act as biological archives, recording information throughout an organism’s life and possibly allowing for the reconstruction of life history events. Concentrations of zinc (Zn) in animal tissues are known to be linked to life history, physiology and reproduction and may be retained in incremental growth structures. This study reconstructed lifetime Zn concentrations in teeth (n = 93) of female Pacific walruses (Odobenus rosmarus divergens) collected from 1932–2016. Zn displayed a characteristic pattern of accumulation, with a change point marking the beginning of a lifelong, linear increase in Zn concentrations. We hypothesized that this change point marks the onset of reproductive maturity. The age at which the change point occurred (agecp) was estimated by counting tooth cementum growth layers. These estimates closely matched literature values of timing of first ovulation in female walruses. Total number of ovulations (estimated from ovary corpora counts from paired tooth/ovary specimens) was closely related to reproductive lifespan (total lifespan – agecp; R2 = 0.70). Further, agecp tracked changes in Pacific walrus population size as a proportion of carrying capacity, decreasing when the population was depleted by commercial hunting and peaking when carrying capacity was exceeded. This novel approach will aid walrus management, and is likely applicable to other species, offering a potentially powerful tool for research, management and conservation of wildlife populations.