Stress and pituitary-adrenocortical manipulation during late pregnancy: effects upon offspring development in mice

Abstract

This thesis describes the effects of crowding during the final third of pregnancy upon development of the offspring in mice, and examines the role of the pituitary-adrenocortical axis as the physiological mechanism of mediation.
In an attempt to confine the effects of. the various experimental manipulations to the prenatal period, and eliminate postnatal variables affecting development, all litters were fostered at birth to control mice. Offspring in litters from crowded mice showed increased perinatal mortality rates and reduced birth weight. Later in development, female offspring from crowded mice show retarded onset of puberty, which is not due to delayed postnatal body weight gain, and in adulthood these animals show disruption of the oestrous cycle typified by shortening of the pro-oestrus stage. Adult male offspring from crowded mice show impaired copulation and reductions in aggression compared with offspring from control mice.
Testosterone propionate therapy in adulthood improved copulation in these animals, but the aggressive responses of fighting male offspring from crowded mice were still deficient compared with those of control offspring even after testosterone propionate treatment. The causes of the syndrome evident in offspring from crowded mice is discussed, and hypoprolactinaemia has been postulated as a general underlying cause of pathology.
Crowding did not severely reduce maternal food intake or shorten the length of pregnancy, but was found to increase plasma corticosterone concentrations during pregnancy. The hypothesis that the effects of crowding during pregnancy upon offspring development are mediated by the maternal pituitary-adrenocortical system was tested. Hormones known to be secreted from this system (e.g. ACTH, corticosterone, progesterone and androstenedione) were administered singly to pregnant mice in an attempt to reproduce the effects of crowding durinci pregnancy upon offspring development. Evidence that the maternal adrenal is required for producing the effects of crowding was inconclusive.