Changes in endocrine and neurochemical profiles in neonatal pigs prenatally exposed to increased maternal cortisol

Abstract

Early life environmental factors are able to influence prenatal development and may cause structural and functional effects on hypothalamic-pituitary-adrenal (HPA) axis and neurotransmitter systems in the offspring. These effects seem to be species specific and may depend on the period of gestation when the factors are effective. Elevated maternal cortisol levels are assumed to play a crucial role as a programming factor during prenatal development. Thus, the present study was performed in order to examine the effects of increased maternal cortisol levels during mid-and late gestation on central and peripheral alterations of the HPA axis and brain neurotransmitter profiles in piglets. Endogenous cortisol release was induced by i.m. administration of ACTH to sows every second day either during mid-(day 49 until 75) or late gestation (day 85 until 107). Controls received injections of saline. ACTH treatment of sows during mid-and late gestation had no effects on the gestation length, the number of total born and the frequency of stillborn piglets. However, ACTH treatment during late gestation caused an increase of birth weight (P!0$04) and affected the organ:body weight ratios (brain and adrenal) in the offspring. There was an impact of increased maternal cortisol on the HPA axis and on central neurotransmitter systems in the offspring. ACTH treatment during mid gestation caused a significant decrease of plasma corticosteroid-binding globulin (CBG; P!0$03) and an increase of the noradrenergic activity in the locus coeruleus (LC) region (P!0$02). Elevated maternal cortisol during late gestation also produced a significant decrease of plasma CBG (P!0$05), but significantly increased the plasma noradrenaline (NA) concentration (P!0$02) and decreased the serotonergic activity in the LC at both postnatal day 1 (P!0$016) and day 28 (P!0$003). Furthermore, there were sex-specific effects of ACTH treatment on plasma CBG, NA and brain monoamine turnover, with more pronounced changes in male offspring. In conclusion, elevated maternal cortisol levels during mid-and late gestation in pigs affect growth, HPA axis and brain neurotransmitter systems in the offspring in a sex-specific manner. The observed alterations in endocrine and neurotransmitter systems are dependent on the gestational period. Late gestation appears to be a more sensitive phase for cortisol-induced programming in pigs. Moreover, the present data show that there are marked developmental differences between laboratory animals and domestic pigs, and highlight the importance of speciesspecific studies on prenatal influences.

Growth and reproductive development of male piglets are more vulnerable to midgestation maternal stress than that of female piglets12

“…When the data from male and female piglets were combined for analysis, sow treatment had no effect on any litter or piglet characteristic. This is in accordance with previous research results showing that during midgestation neither the authentic stressors of rough handling (Lay et al, 2008) and mixing (Jarvis et al, 2006;Rutherford et al, 2009), nor the artificial stressors ACTH (Haussmann et al, 2000;Schneider et al, 2004;Brussow et al, 2005;Kanitz et al, 2006;Otten et al, 2007) and HCA (Kranendonk et al, 2006) affected gestation length (Haussmann et al, 2000;Jarvis et al, 2006;Kanitz et al, 2006;Kranendonk et al, 2006;Otten et al, 2007;Lay et al, 2008), litter size (Haussmann et al, 2000;Schneider et al, 2004;Brussow et al, 2005;Kanitz et al, 2006;Kranendonk et al, 2006;Otten et al, 2007;Lay et al, 2008;Rutherford et al, 2009), or number of stillborn pigs (Haussmann et al, 2000;Jarvis et al, 2006;Kranendonk et al, 2006;Otten et al, 2007;Lay et al, 2008).…”

The cortisol response to ACTH in pigs, heritability and influence of corticosteroid-binding globulin

“…Cooper et al, 2009) but their biological mechanisms have not been thoroughly investigated. It is worth noting, however, that several authors have shown that the HPA axis activity was shaped by prenatal influences in a sex-specific manner (Kanitz et al, 2006;Kranendonck et al, 2008;Collier et al, 2011;Óvilo et al, 2014).…”

Maternal backfat depth in gestating sows has a greater influence on offspring growth and carcass lean yield than maternal feed allocation during gestation

“…The latter is in accordance with findings by Kranendonk et al (2006), who found that piglets born from cortisol-treated sows had a lower peak cortisol response compared with piglets born from noncortisol-treated sows. In addition, piglets born from sows exposed to elevated cortisol concentrations during pregnancy had altered brain neurotransmitter profiles, such as an increased noradrenergic activity in the locus coeruleus region of the hypothalamus, and tended to have reduced glucocorticoid receptor binding (Kanitz et al, 2006).…”