Transgenerational transmission of a stress-coping phenotype programmed by early-life stress in the Japanese quail

This study was funded by a BBSRC David Phillips Research Fellowship to K.A. Spencer (BB/L002264/1).An interesting aspect of developmental programming is the existence of transgenerational effects that influence offspring characteristics and performance later in life. These transgenerational effects have been hypothesized to allow individuals to cope better with predictable environmental fluctuations and thus facilitate adaptation to changing environments. Here, we test for the first time how early-life stress drives developmental programming and transgenerational effects of maternal exposure to early-life stress on several phenotypic traits in their offspring in a functionally relevant context using a fully factorial design. We manipulated pre- and/or post-natal stress in both Japanese quail mothers and offspring and examined the consequences for several stress-related traits in the offspring generation. We show that pre-natal stress experienced by the mother did not simply affect offspring phenotype but resulted in the inheritance of the same stress-coping traits in the offspring across all phenotypic levels that we investigated, shaping neuroendocrine, physiological and behavioural traits. This may serve mothers to better prepare their offspring to cope with later environments where the same stressors are experienced.Publisher PDFPeer reviewe

Early-life adversity programs long-term cytokine and microglia expression within the HPA axis in female Japanese quail

This work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC grant no. BB/L002264/1 to K.A.S., C.Z. and S.D.H.), a David Phillips Research Fellowship (K.A.S.) and an EASTBIO BBSRC Doctoral Training Programme studentship (grant no. BB/J01446X/1 to D.J.W., supervisors K.A.S., S.D.H.). Data are available from Mendeley (Walker, 2019): http://dx.doi.org/10.17632/ 6r7d2pg2zk.1Stress exposure during prenatal and postnatal development can have persistent and often dysfunctional effects on several physiological systems, including immune function, affecting the ability to combat infection. The neuroimmune response is inextricably linked to the action of the hypothalamic–pituitary–adrenal (HPA) axis. Cytokines released from neuroimmune cells, including microglia, activate the HPA axis, while glucocorticoids in turn regulate cytokine release from microglia. Because of the close links between these two physiological systems, coupled with potential for persistent changes to HPA axis activity following developmental stress, components of the neuroimmune system could be targets for developmental programming. However, little is known of any programming effects of developmental stress on neuroimmune function. We investigated whether developmental stress exposure via elevated prenatal corticosterone (CORT) or postnatal unpredictable food availability had long-term effects on pro- (IL-1β) and anti-inflammatory (IL-10) cytokine and microglia-dependent gene (CSF1R) expression within HPA axis tissues in a precocial bird, the Japanese quail (Coturnix japonica). Following postnatal stress, we observed increased IL-1β expression in the pituitary gland, reduced IL-10 expression in the amygdala and hypothalamus, and reduced CSF1R expression within the hypothalamus and pituitary gland. Postnatal stress disrupted the ratio of IL-1β:IL-10 expression within the hippocampus and hypothalamus. Prenatal stress only increased IL-1β expression in the pituitary gland. We found no evidence for interactive or cumulative effects across life stages on basal cytokine and glia expression in adulthood. We show that postnatal stress may have a larger impact than elevated prenatal CORT on basal immunity in HPA-axis-specific brain regions, with changes in cytokine homeostasis and microglia abundance. These results provide evidence for postnatal programming of a pro-inflammatory neuroimmune phenotype at the expense of reduced microglia, which could have implications for central nervous system health and subsequent neuroimmune responses.Publisher PDFPeer reviewe

Chronological age, biological age, and individual variation in the stress response in the European starling : a follow-up study

This research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) under grants BB/J016446/1 and BB/J016292/1; a doctoral training studentship to Annie Gott; and a David Phillips fellowship to Karen Spencer. The project has also received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. AdG 666669 (COMSTAR)).The strength of the avian stress response declines with age. A recently published study of European starlings (Sturnus vulgaris) found that a marker of biological age predicted the strength of the stress response even in individuals of the same chronological age. Specifically, birds that had experienced greater developmental telomere attrition (DTA) showed a lower peak corticosterone (CORT) response to an acute stressor, and more rapid recovery of CORT levels towards baseline. Here, we performed a follow-up study using the same capture-handling-restraint stressor in a separate cohort of starlings that had been subjected to a developmental manipulation of food availability and begging effort. We measured the CORT response at two different age points (4 and 18 months). Our data suggest a decline in the strength of the CORT response with chronological age: peak CORT was lower at the second age point, and there was relatively more reduction in CORT between 15 and 30 min. Individual consistency between the two age points was low, but there were modest familial effects on baseline and peak CORT. The manipulation of begging effort affected the stress response (specifically, the reduction in CORT between 15 and 30 min) in an age-dependent manner. However, we did not replicate the associations with DTA observed in the earlier study. We meta-analysed the data from the present and the earlier study combined, and found some support for the conclusions of the earlier paper.Publisher PDFPeer reviewe

Pre-natal exposure to glucocorticoids causes changes in developmental circadian gene expression (dataset)

Excel spreadsheet of qPCR result