Long-term gender-specific effects of manipulation during pregnancy immune and endocrine responsiveness in rat offspring

Exposure to synthetic glucocorticoids (GCs) or other stimuli around birth may affect neuroendocrine and immune responsiveness in the offspring. Experiments were conducted to investigate whether maternal manipulation with saline or with GCs alters the corticosterone (CORT) response to a mild stressor in the offspring, and whether maternal manipulation results in long- term altered in vivo humoral and cellular immune responsiveness in the offspring. Pregnant rats were given dexamethasone (DEX, 1.2 mg/kg body weight, i.p.) or saline (SAL) at day 17 and 19 of gestation. A third group of pregnant rats was left undisturbed (UNTR-group). After maternal DEX treatment, no altered CORT response was seen to a novel environment at 20 days of age, as compared to both the SAL-treated group and the UNTR-group. However, saline administration to pregnant rats caused an increased CORT response in female offspring, but not male offspring, as compared to the UNTR-group (P≤0.01). Furthermore, no effects of maternal DEX exposure were seen on IgG2a production after immunization with a conjugated pneumococcal polysaccharide (PPS-14-CRM₁₉₇) at 6 weeks of age. However maternal SAL treatment enhanced anti-PPS-14 IgG2a antibody levels in female offspring, but not in male offspring, as compared to the UNTR-group (P≤0.05). Cellular immune responses were measured by an oxazolone-induced contact hypersensitivity response (CHS-response), at 8 weeks of age. Maternal SAL treatment increased the CHS response in adult male rats, but not in female rats, as compared to both the UNTR-group and the DEX-group (P≤0.005). These data suggest that manipulations during late pregnancy not only affect endocrine responsiveness, but also influence immune responsiveness in the rat offspring. Furthermore, these effects may be long-term and gender-specific.