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.