Elevated glucocorticoids during the ovarian follicular phase predict conception in wild female chacma baboons.

Mating related behavior during ovarian cycling can be energetically demanding and constitute a significant stressor, requiring physiological responses to mediate investment in reproduction. To better understand the proximate mechanisms underlying these responses, we examine hormonal and behavioral variation across the ovarian cycle during conceptive and nonconceptive cycles in wild female chacma baboons (Papio ursinus). We quantified immunoreactive fecal estradiol, progesterone, and cortisol metabolites for 21 adult females, and calculated activity budgets and rates of received aggression from over 5000 15-min behavioral samples. We found conception to be associated with higher concentrations of both estradiol and cortisol during the follicular phase, but no difference in progesterone between conceptive and nonconceptive cycles for either the follicular or luteal phase. While females spent less time feeding during the follicular compared to the luteal phase, we found no difference in time spent feeding, moving, or copulating between conceptive and nonconceptive cycles of the same phase. Rates of received aggression also were similar across the ovarian cycle, with no difference between conceptive and nonconceptive cycles. Finally, we found positive associations between cortisol and estradiol, indicating that glucocorticoids (GCs) do not suppress hypothalamic-pituitary-gonadal (HPG) activity and reproductive function in this context. Overall, our results suggest that elevated GCs may play an adaptive role in mobilizing energy during sexually receptive periods of ovarian cycling.

Osteogenic Competence and Potency of the Bone Induction Principle: Inductive Substrates That Initiate "Bone: Formation by Autoinduction".

ABSTRACT: The de novo induction of bone has always been a fascinating phenomenon, keeping skeletal reconstructionists and cellular developmental biologists continuously engaged to finally provide a molecular and cellular approach to the induction of bone formation. A significant advancement was made by the purification and cloning of the human recombinant bone morphogenetic proteins, members of the transforming growth factor-ß supergene family. Human bone morphogenetic proteins are powerful inducers of bone in animal models including nonhuman primates. Translation in clinical contexts has however, proven to be surprisingly difficult. This review also describes the significant induction of bone formation by the human transforming growth factor-ß3 when implanted in heterotopic intramuscular sites of the Chacma baboon Papio ursinus. Large mandibular defects implanted with 250 mg human transforming growth factor-ß3 in human patients showed significant osteoinduction; however, the induction of bone was comparatively less than the induction of bone in P ursinus once again highlighting the conundrum of human osteoinduction: is the bone induction principle failing clinical translation?

Simultaneous investigation of urinary and faecal glucocorticoid metabolite concentrations reveals short- versus long-term drivers of HPA-axis activity in a wild primate (Papio ursinus).

Glucocorticoids (GCs), a class of steroid hormones released through activation of the hypothalamic-pituitary-adrenal (HPA) axis, perform many vital functions essential for survival, including orchestrating an organism's response to stressors by modulating physiological and behavioural responses. Assessing changes and variation in GC metabolites from faecal or urine samples allows for the non-invasive monitoring of HPA-axis activity across vertebrates. The time lag of hormone excretion differs between these sample matrices, which has implications for their suitability for studying effects of different temporal nature on HPA-axis activity. However, simultaneous comparisons of predictors of faecal and urinary GC metabolites (fGCs and uGCs, respectively) are lacking. To address this gap, we employ frequent non-invasive sampling to investigate correlates of fGCs and uGCs in wild chacma baboons (Papio ursinus) (n = 17), including long-term (dominance rank, season, female reproductive state) and short-term (time of day, daily weather conditions) factors. Correlated with increasing day length, fGCs gradually decreased from winter to summer. No seasonal effect on uGCs was found but 'rain days' were associated with increased uGCs. Pregnant females had significantly higher fGCs compared to cycling and lactating females, whereas uGCs were not statistically different across reproductive states. A circadian effect was observed in uGCs but not in fGCs. Dominance rank did not affect either fGCs or uGCs. Our study highlights the difference in inherent fluctuation between uGCs and fGCs and its potential consequences for HPA-axis activity monitoring. While uGCs offer the opportunity to study short-term effects, they undergo more pronounced fluctuations, reducing their ability to capture long-term effects. Given the increasing use of urine for biological monitoring, knowledge of this potential limitation is crucial. Where possible, uGCs and fGCs should be monitored in tandem to obtain a comprehensive understanding of short- and long-term drivers of HPA-axis activity.

Energetics at the urban edge: Environmental and individual predictors of urinary C-peptide levels in wild chacma baboons (Papio ursinus).

As human-modified landscapes encroach into natural habitats, wildlife face a reduction in natural food sources but also gain access to calorie-rich, human-derived foods. However, research into the energetics of wildlife living within and adjacent to urban and rural landscapes is lacking. C-peptide - a proxy for insulin production and a diagnostic tool for assessing pancreatic function in humans and domestic animals - can be quantified non-invasively from urine (uCP) and may provide a way to investigate the energetic correlates of living in human-altered landscapes. UCP is increasingly used in studies of primate energetics, and here we examine predictors of variation in uCP levels in n = 17 wild chacma baboons (Papio ursinus) living at the urban edge on the Cape Peninsula, South Africa. We find that uCP was positively associated with food provisioning and negatively with night fasting. UCP levels were comparable between winter and summer but significantly lower during spring, possibly driven by consumption of energy-rich seeds during summer and more human-derived foods during winter. UCP was elevated in pregnant females and similar for lactating and cycling females. We find no effect of dominance rank on uCP. Samples collected with synthetic Salivettes had significantly lower uCP levels than directly pipetted samples. Overall, our results indicate that uCP is a reliable, non-invasive measure of energy balance and intake in baboons, and suggest potential energetic benefits of living at the urban edge. More broadly, studies of uCP may offer unique insight into the environmental control of hormone-behaviour relationships in species crossing natural and urban environments.

Social behavior and patterns of testosterone and glucocorticoid levels differ between male chacma and Guinea baboons.

In multi-male, multi-female groups of mammals, males usually compete aggressively over access to females. However, species vary in the intensity of male contest competition, which has been linked to differences in testosterone and glucocorticoid profiles. Chacma (Papio ursinus) and Guinea (P. papio) baboons constitute an intriguing model to examine variation in male competition and male endocrine correlates, because of the differences in their social systems. Chacma baboons live in stable female-bonded groups with linear male dominance hierarchies and a high male mating skew, whereas Guinea baboons live in male-bonded, multi-level societies. We recorded male behavior and assayed testosterone (fT) and glucocorticoid metabolite (fGC) levels from fecal samples in one population of each species. Male chacma baboons were more frequently involved in agonistic interactions, and dominance relationships were more consistent than in Guinea baboons, where we could not detect linear hierarchies. Notably, male chacma baboons were also more aggressive towards females, indicating an overall higher aggressiveness in this species. In contrast, male Guinea baboons showed higher levels of affiliative interactions and spatial tolerance. High-ranking and consorting male chacma baboons showed elevated fGC levels and also tended to show elevated fT levels, but there was no effect of consortship in Guinea baboons. Agonism was not related to hormone levels in either species. Thus, predictors of fT and fGC levels in Guinea baboons seem to differ from chacma baboons. Our results support the view that different social systems create differential selection pressures for male aggression, reflected by different hormone profiles.

Soil consumed by chacma baboons is low in bioavailable iron and high in clay.

Despite widespread consumption of soil among animals, the role of geophagy in health maintenance remains an enigma. It has been hypothesized that animals consume soil for supplementation of minerals and protection against toxins. Most studies determine only the total elemental composition of soil, which may not reflect the amount of minerals available to the consumer. Our aim was to test these hypotheses by evaluating the bioavailability of iron in soil consumed by chacma baboons, using a technique that simulates digestion and adsorption. Our results indicate that, despite variation in absolute iron concentration of soil samples, actual iron bioavailability was low while clay content was quite high. This suggests that iron supplementation is unlikely to be the primary motivation for geophagy in this population, and that detoxification is a plausible explanation. This study demonstrates that more research on bioavailability and clay composition is needed to determine the role geophagy plays in health maintenance.

Induction of bone formation by transforming growth factor-beta2 in the non-human primate Papio ursinus and its modulation by skeletal muscle responding stem cells.

OBJECTIVES: Four adult non-human primates Papio ursinus were used to study induction of bone formation by recombinant human transforming growth factor-beta(2) (hTGF-beta(2)) together with muscle-derived stem cells. MATERIALS AND METHODS: The hTGF-beta(2) was implanted in rectus abdominis muscles and in calvarial defects with and without addition of morcellized fragments of striated muscle, harvested from the rectus abdominis or temporalis muscles. Expression of osteogenic markers including osteogenic protein-1, bone morphogenetic protein-3 and type IV collagen mRNAs from generated specimens was examined by Northern blot analysis. RESULTS: Heterotopic intramuscular implantation of 5 and 25 microg hTGF-beta(2) combined with 100 mg of insoluble collagenous bone matrix yielded large corticalized mineralized ossicles by day 30 with remodelling and induction of haematopoietic marrow by day 90. Addition of morcellized rectus abdominis muscle to calvarial implants enhanced induction of bone formation significantly by day 90. CONCLUSIONS: In Papio ursinus, in marked contrast to rodents and lagomorphs, hTGF-beta(2) induced large corticalized and vascularized ossicles by day 30 after implantation into the rectus abdominis muscle. This striated muscle contains responding stem cells that enhance the bone induction cascade of hTGF-beta(2). Induction of bone formation by hTGF-beta(2) in the non-human primate Papio ursinus may occur as a result of expression of bone morphogenetic proteins on heterotopic implantation of hTGF-beta(2); the bone induction cascade initiated by mammalian TGF-beta proteins in Papio ursinus needs to be re-evaluated for novel molecular therapeutics for induction of bone formation in clinical contexts.

Copeptin, a stable peptide of the arginine vasopressin precursor, is elevated in hemorrhagic and septic shock.

Arginine vasopressin (AVP) levels are increased in hemorrhagic and septic shock. Measurement of AVP levels has limitations due to its short half-life and cumbersome detection method. Copeptin is a more stable peptide derived from the same precursor molecule. We evaluated the plasma copeptin concentration in two independent studies: first, in an experimental baboon model of hemorrhagic shock, and second, in a prospective observational study of 101 consecutive critically ill patients at a university hospital. Copeptin was measured with a newly developed sandwich immunoassay using two polyclonal antibodies to the C-terminal region (amino acid sequence 132-164) of pre-pro-AVP. Copeptin concentrations in hemorrhagic shock increased markedly from median (range) of 7.5 [2.7-13) to 269 pM (241-456 pM). After reperfusion, copeptin levels dropped within hours to a plateau of 27 pM (15-78 pM). In the critically ill patient cohort, copeptin values increased significantly with the severity of the disease and were in patients without sepsis [27.6 pM [2.3-297 pM]), in sepsis [50.0 pM [8.5-268 pM]), in severe sepsis [73.6 pM [15.3-317 pM]), and in septic shock [171.5 pM (35.1-504 pM] compared with 4.1 pM (1.0-13.8 pM) in healthy controls (P for all vs. controls <0.001). On admission, circulating copeptin levels were higher in nonsurvivors (171.5 pM, 46.5-504.0 pM) as compared with survivors (86.8 pM, 8.5-386.0 pM; P = 0.01). Copeptin levels correlated with basal cortisol levels (r = 0.42; P < 0.001) and osmolality (r = 0.42; P < 0.001). In a logistic regression model including other covariates besides copeptin (e.g., determinants of fluid status) on survival, serum copeptin levels were the only independent significant predictor of outcome (P = 0.03). Copeptin concentrations are elevated in hemorrhagic and septic shock. Copeptin was higher on admission in nonsurvivors as compared with survivors, suggesting copeptin as a prognostic marker in sepsis. The availability of a reliable assay for the measurement of AVP release can also prove useful for the assessment of fluid and osmosis status in various diseases.

Bone induction by recombinant human osteogenic protein-1 (hOP-1, BMP-7) in the primate Papio ursinus with expression of mRNA of gene products of the TGF-beta superfamily.

Predictable bone induction in clinical contexts requires information on the expression and cross regulation of gene products of the transforming growth factor-beta (TGF-beta) superfamily elicited by single applications of each recombinant human bone morphogenetic/osteogenic proteins (BMPs/OPs). Using the calvarium and the rectus abdominis muscle of adult baboons Papio ursinus as a model for tissue induction and morphogenesis, this study investigated the induction of bone morphogenesis by gamma-irradiated hOP-1 delivered by gamma-irradiated bovine insoluble collagenous bone matrix, the hOP-1 osteogenic device, for bone induction in heterotopic and orthotopic sites of the primate Papio ursinus and the expression patterns of OP-1, collagen type IV, BMP-3 and TGFbeta1mRNAs elicited by increasing single applications of doses of the hOP-1 osteogenic devices (0.1, 0.5 and 2.5 mg hOP-1/g of matrix) applied heterotopically in the rectus abdominis muscle and orthotopically in 48 calvarial defects of 12 adult baboons. Histology and histomorphometry on serial undecalcified sections prepared from the specimens harvested on day 15, 30 and 90 showed that all the doses of the hOP-1 osteogenic device induced bone formation culminating in complete calvarial regeneration by day 90. Type IV collagen mRNA expression, a marker of angiogenesis, was strongly expressed in both heterotopic and orthotopic tissues. High levels of expression of OP-1 mRNA demonstrated autoinduction of OP-1 mRNAs. Expression levels of BMP-3 mRNA varied from tissues induced in heterotopic vs. orthotopic sites with high expression in rapidly forming heterotopic ossicles together with high expression of type IV collagen mRNA. The temporal and spatial expressions of TGF-beta1 mRNAindicate a specific temporal transcriptional window during which expression of TGF-beta1 is mandatory for successful and optimal osteogenesis. The induction of bone by hOP-1 in Papio ursinus develops as a mosaic structure with distinct spatial and temporal patterns of gene expression of members of the TGF-beta superfamily that singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis.