EFFECTS OF SHORT-TERM DEXAMETHASONE TREATMENT DURING PREGNANCY ON THEDEVELOPMENT OF THE IMMUNE-SYSTEM AND THE HYPOTHALAMOPITUITARY-ADRENALAXIS IN THE RAT
Jm. Bakker et al., EFFECTS OF SHORT-TERM DEXAMETHASONE TREATMENT DURING PREGNANCY ON THEDEVELOPMENT OF THE IMMUNE-SYSTEM AND THE HYPOTHALAMOPITUITARY-ADRENALAXIS IN THE RAT, Journal of neuroimmunology, 63(2), 1995, pp. 183-191
The effects of glucocorticoid (GC) treatment on the mature immune and
neuroendocrine system are known to be reversible. However, prenatal GC
exposure may have irreversible consequences on the development of the
newborn. In this study, possible long-lasting effects of short-term p
renatal GC treatment were examined on the developing thymus, spleen an
d hypothalamo-pituitary adrenal axis (HPA axis). Female rats were give
n dexamethasone (DEX, 400 mu g, i.p.) on day 17 and 19 of pregnancy an
d offspring was studied at several time intervals (1-20 days) after bi
rth, for examination of thymus, spleen, hypothalamus and blood plasma.
Examination of thymus and spleen revealed that prenatal exposure to D
EX resulted in decreased T cell numbers in thymus and spleen on day 1
after birth. Thymus regeneration after DEX exposure both during pregna
ncy and in adult life was completed after 24 days. However, the kineti
cs of regeneration of the thymi after prenatal DEX exposure were diffe
rent from that seen after DEX in adult life. Whereas DEX treatment dur
ing pregnancy resulted in an increased ratio of CD4(+)/CD8(-) thymocyt
es over CD4(-)/CD8(+) thymocytes compared to control groups on day 7 a
nd day 20 after birth (time X treatment interaction; P < 0.05), DEX tr
eatment in adult life did not change this ratio. T cell numbers in the
spleen were significantly decreased at all neonatal ages studied. Reg
arding the hypothalamus, prenatal exposure to DEX altered the pattern
of neonatal changes in peptide expression in corticotropin-releasing h
ormone neurons, with a selective reduction in CRH storage in the media
n eminence (7 and 9 days after birth) and an increase in AVP storage (
9 and 20 days after birth). The ratio of AVP over CRH was significantl
y increased at all developmental ages studied. No effects were seen on
basal ACTH and corticosterone levels in plasma. In conclusion, the ki
netics of thymus regeneration after DEX exposure during pregnancy were
different from that seen after DEX exposure in adult life. Prenatal D
EX exposure also seemed to delay the migration of T cells into the spl
een. Furthermore, prenatal DEX treatment exerted major effects on hypo
thalamic CRH neurons that maintained for at least 20 days after birth,
which points towards an enhanced stress responsiveness of the HPA axi
s in later life.