Effects of social housing of sexually mature male cynomolgus monkeys during general and reproductive toxicity evaluation

Niehoff, Marc; Bergmann, Martin; Weinbauer, Gerhard F.

doi:10.1016/j.reprotox.2009.09.007

Cited by 21 publications

(15 citation statements)

References 26 publications

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“…It has been proposed that developmental history contributes to individual differences in reproductive behavior, and that stress exposures in adolescence may be a factor in sexual sluggishness (McCormick and Green, 2013). However, in rodents, a state of dominance causes an increase in testis weights (Niehoff et al, 2010). Given that testosterone modulates the expression of BDNF protein and its receptor (Fargo et al, 2009), and that testis mass is an indicator of testosterone level (Lee et al, 2001), we speculate that testosterone might have contributed to the higher serum BDNF levels observed in the EC animals.…”

Section: Discussionmentioning

confidence: 99%

Post‐weaning environmental enrichment improves BDNF response of adult male rats

Mosaferi

Babri

Mohaddes

et al. 2015

Intl J of Devlp Neuroscience

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The environment could have long lasting effects on the individual phenotype through developmental plasticity. Early environmental enrichment exerts profound biological effects, most of which are quite beneficial ones. To explore the enduring effects of rearing condition quality on BDNF(1) responses, we reared male Wistar rats from weaning to young-adulthood in three different environmental conditions: 1. Enriched 2. Standard, and 3. Isolated. Then, at the age of 16 weeks, 10 rats from each group were randomly chosen and allocated to six common mix cages. They were kept together for 14 weeks. At the end of the experiment, each rat received ten inescapable foot-shocks. Twelve hours later, the BDNF contents of the amygdala and CA1 sub-region of the dorsal hippocampus were measured. The serum BDNF levels, hematocrit values as well as brain and testis weights were also measured. Results showed that the environmental enrichment led to stronger dorsal hippocampal BDNF response and higher serum BDNF levels, while rats from standard laboratory condition showed higher amygdala BDNF response. Also, enriched animals showed higher brain weight compared to isolation reared rats as well as higher testis weight and hematocrit value compared to animals reared in standard laboratory condition. Rats showed less body weights in isolated condition. In conclusion, the BDNF profile of enriched animals might represent the neurobiological correlate of resilience phenotype under a stressful situation.

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Section: Discussionmentioning

confidence: 99%

Post‐weaning environmental enrichment improves BDNF response of adult male rats

Mosaferi

Babri

Mohaddes

et al. 2015

Intl J of Devlp Neuroscience

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“…Apart from the daily animal care and use aspects, changing from individual to social housing raises significant implications for general and special toxicity studies using mature animals and having reproductive toxicity evaluation endpoints. Group formation markedly, albeit transiently, altered body weights and testicular size in male cynomolgus monkeys (Niehoff et al, 2009) and transiently prolonged or inhibited menstrual cycles in female animals (Weinbauer et al, 2008a). All inhibitory effects reverted within about 26 weeks.…”

Section: Current and Future Trends In Nhp Dartmentioning

confidence: 95%

Developmental and reproductive toxicology studies in nonhuman primates

Chellman¹,

Bussiere

Makori

et al. 2009

Birth Defects Research Pt B

Self Cite

136

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Developmental and reproductive toxicology testing in nonhuman primates (NHPs) has become more common due to the increasing number of biopharmaceuticals in drug development, since NHPs are frequently the only species to express pharmacologic responses similar to humans. NHPs may also be used to help resolve issues associated with small-molecule reproductive toxicology in traditional species (rodents and rabbits). Adequate designs in NHP are presented for developmental toxicity (embryo-fetal development, pre-postnatal development, enhanced pre-postnatal development), reproductive toxicity (male and female), and juvenile toxicity studies. Optional parameters that may be included in these studies are discussed, as are new study designs that consolidate multiple aspects of the reproductive assessment and thereby conserve the limited supply of sexually mature NHPs available for testing. The details described will assist scientists in pharmaceutical, regulatory, and contract research organizations who are involved in conducting these unique studies to optimize their design based on case-by-case considerations.

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“…However, initial establishment of social hierarchy in recently introduced groups of monkeys is stressful and can result in dramatic changes in reproductive parameters. Niehoff, Bergmann, and Weinbauer (2010) reported a 45% decrease in testis volume of subordinate male cynomolgus monkeys following introduction into a social grouping. Most of the decrease occurred during the first 3 months of social housing.…”

Section: Social/hierarchical Stress In Nonhuman Primatesmentioning

confidence: 99%

Interpreting Stress Responses during Routine Toxicity Studies

et al. 2013

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Stress often occurs during toxicity studies. The perception of sensory stimuli as stressful primarily results in catecholamine release and activation of the hypothalamic-pituitary-adrenal (HPA) axis to increase serum glucocorticoid concentrations. Downstream effects of these neuroendocrine signals may include decreased total body weights or body weight gain; food consumption and activity; altered organ weights (e.g., thymus, spleen, adrenal); lymphocyte depletion in thymus and spleen; altered circulating leukocyte counts (e.g., increased neutrophils with decreased lymphocytes and eosinophils); and altered reproductive functions. Typically, only some of these findings occur in a given study. Stress responses should be interpreted as secondary (indirect) rather than primary (direct) test article-related findings. Determining whether effects are the result of stress requires a weight-of-evidence approach. The evaluation and interpretation of routinely collected data (standard in-life, clinical pathology, and anatomic pathology endpoints) are appropriate and generally sufficient to assess whether or not changes are secondary to stress. The impact of possible stress-induced effects on data interpretation can partially be mitigated by toxicity study designs that use appropriate control groups (e.g., cohorts treated with vehicle and subjected to the same procedures as those dosed with test article), housing that minimizes isolation and offers environmental enrichment, and experimental procedures that minimize stress and sampling and analytical bias.This article is a comprehensive overview of the biological aspects of the stress response, beginning with a Summary (Section 1) and an Introduction (Section 2) that describes the historical and conventional methods used to characterize acute and chronic stress responses. These sections are followed by reviews of the primary systems and parameters that regulate and/or are influenced by stress, with an emphasis on parameters evaluated in toxicity studies:

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Effects of social housing of sexually mature male cynomolgus monkeys during general and reproductive toxicity evaluation

Cited by 21 publications

References 26 publications

Post‐weaning environmental enrichment improves BDNF response of adult male rats

Post‐weaning environmental enrichment improves BDNF response of adult male rats

Developmental and reproductive toxicology studies in nonhuman primates

Interpreting Stress Responses during Routine Toxicity Studies

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