Markedly Elevated Antibody Responses in Wild versus Captive Spotted Hyenas Show that Environmental and Ecological Factors Are Important Modulators of Immunity

<div><p>Evolutionary processes have shaped the vertebrate immune system over time, but proximal mechanisms control the onset, duration, and intensity of immune responses. Based on testing of the hygiene hypothesis, it is now well known that microbial exposure is important for proper development and regulation of the immune system. However, few studies have examined the differences between wild animals in their natural environments, in which they are typically exposed to a wide array of potential pathogens, and their conspecifics living in captivity. Wild spotted hyenas (<i>Crocuta crocuta</i>) are regularly exposed to myriad pathogens, but there is little evidence of disease-induced mortality in wild hyena populations, suggesting that immune defenses are robust in this species. Here we assessed differences in immune defenses between wild spotted hyenas that inhabit their natural savanna environment and captive hyenas that inhabit a captive environment where pathogen control programs are implemented. Importantly, the captive population of spotted hyenas was derived directly from the wild population and has been in captivity for less than four generations. Our results show that wild hyenas have significantly higher serum antibody concentrations, including total IgG and IgM, natural antibodies, and autoantibodies than do captive hyenas; there was no difference in the bacterial killing capacity of sera collected from captive and wild hyenas. The striking differences in serum antibody concentrations observed here suggest that complementing traditional immunology studies, with comparative studies of wild animals in their natural environment may help to uncover links between environment and immune function, and facilitate progress towards answering immunological questions associated with the hygiene hypothesis.</p></div

Spotted hyaenas and the sexual spectrum: reproductive endocrinology and development.

The spotted hyaena (Crocuta crocuta) is a unique species, even amongst the Hyaenidae. Extreme clitoral development in female spotted hyaenas challenges aspects of the accepted framework of sexual differentiation and reproductive function. They lack a vulva and instead urinate, copulate and give birth through a single, long urogenital canal that traverses a clitoris superficially resembling a penis. Recent and historical evidence is reviewed to describe our changing understanding of the biology of this species. Expanding upon observations from hyaenas in nature, much has been learned from studies utilising the captive colony at the University of California, Berkeley. The steroid environment of pregnancy is shaped by placental androgen and oestrogen secretion and a late gestational increase in sex hormone binding globulin, the regulated expression and steroid-binding characteristics of which are unique within the Hyaenidae. While initial external genital development is largely free of androgenic influence, the increase in testosterone concentrations in late gestation influences foetal development. Specifically, anti-androgen (AA) treatment of pregnant females reduced the developmental influence of androgens on their foetuses, resulting in reduced androstenedione concentrations in young females and easier birth through a 'feminised' clitoris, but precluded intromission and mating by 'feminised' male offspring, and altered social interactions. Insight into the costs and benefits of androgen exposure on spotted hyaena reproductive development, endocrinology and behaviour emphasises the delicate balance that sustains reproductive success, forces a re-evaluation of how we define masculine vs feminine sexual characteristics, and motivates reflection about the representative value of model species

Relative concentrations of total IgG and IgM.

<p>Total IgG (A) and total IgM (B) are significantly higher in wild hyenas (n = 14) than in captive hyenas (n = 15). Females are indicated by open circles and males by filled circles. ***<i>p</i> < 0.001.</p

Bacterial killing capacity (BKC) of serum.

<p>BKC is similar in captive (n = 15) and wild (n = 14) hyenas. Females are indicated by open circles and males by filled circles.</p

Spotted hyaenas and the sexual spectrum: reproductive endocrinology and development.

The spotted hyaena (Crocuta crocuta) is a unique species, even amongst the Hyaenidae. Extreme clitoral development in female spotted hyaenas challenges aspects of the accepted framework of sexual differentiation and reproductive function. They lack a vulva and instead urinate, copulate and give birth through a single, long urogenital canal that traverses a clitoris superficially resembling a penis. Recent and historical evidence is reviewed to describe our changing understanding of the biology of this species. Expanding upon observations from hyaenas in nature, much has been learned from studies utilising the captive colony at the University of California, Berkeley. The steroid environment of pregnancy is shaped by placental androgen and oestrogen secretion and a late gestational increase in sex hormone binding globulin, the regulated expression and steroid-binding characteristics of which are unique within the Hyaenidae. While initial external genital development is largely free of androgenic influence, the increase in testosterone concentrations in late gestation influences foetal development. Specifically, anti-androgen (AA) treatment of pregnant females reduced the developmental influence of androgens on their foetuses, resulting in reduced androstenedione concentrations in young females and easier birth through a 'feminised' clitoris, but precluded intromission and mating by 'feminised' male offspring, and altered social interactions. Insight into the costs and benefits of androgen exposure on spotted hyaena reproductive development, endocrinology and behaviour emphasises the delicate balance that sustains reproductive success, forces a re-evaluation of how we define masculine vs feminine sexual characteristics, and motivates reflection about the representative value of model species

Immune defense component model modified from Schmid-Hempel and Ebert [28].

<p>Patterns shown here are hypothesized based on existing literature and the locations within the plot were adjusted based on the results of this study. Bacterial killing capacity (BKC) is the least specific defense and also falls at the constitutive end of the x-axis. Specific IgG falls near the induced end of the x-axis, and is the most specific defense represented here. Anti-nuclear antibodies (ANAs) are specific to nuclear proteins and nucleic acids and can be induced following ligation of endosomal pattern recognition receptors. Natural IgG and IgM are non-specific and can be produced independent of CD4 T cell help. The dashed lines represent primary exposure (left) and secondary (right) exposure.</p

Relative concentrations of anti-KLH natural antibodies.

<p>Anti-KLH natural IgG (A) is significantly higher in wild hyenas (n = 14) than in captive hyenas (n = 11), but there is no difference in anti-KLH natural IgM (B) between wild (n = 14) captive (n = 11) hyenas. Females are indicated by open circles and males by filled circles. *** <i>p</i> < 0.001.</p