Prenatal Lipopolysaccharide Reduces Social Behavior in Male Offspring

Objective: This study investigated the relationship between maternal sickness behavior during pregnancy and offspring development and behavior. Methods: Pregnant Wistar rats were administered with lipopolysaccharide (LPS, 100 mu g/kg, i.p.) on gestation day (GD) 9.5. Dams` sickness behavior was analyzed, and at birth, offspring number and weight were evaluated. Male offspring was evaluated through physical development, play behavior, adult social interaction, plus maze studies and morphological analysis of the brain. Results: Results, with respect to the control group, showed that: (1) LPS decreased general activity, food intake, and weight gain in dams, but no pyrexia was observed following treatment; (2) LPS reduced litter size, but no alterations in physical development were observed; (3) LPS reduced play behavior parameters in baby rats; (4) LPS decreased adult social interaction; (5) no alterations were observed between groups on plus maze studies; (6) no differences were observed between groups on morphological analyses of the brain. Conclusion: These data reveal that LPS administered on GD 9.5 impaired male offspring`s social behavior in infancy and adulthood. These results may be related to an alteration in motivational states or/and increased anxiety. Copyright (C) 2010 S. Karger AG, Basel

Prenatal Lipopolysaccharide Exposure Affects Maternal Behavior and Male Offspring Sexual Behavior in Adulthood

Objective: This study investigates the effects of prenatal lipopolysaccharide (LPS) exposure on the maternal behavior of pregnant rats and the physical development and sexual behavior of their male offspring in adulthood. Methods: For two experiments, pregnant rats were injected with LPS (250 mu g/kg, i.p.) on gestation day (GD) 21. In the first experiment, the maternal behavior (postnatal day, PND, 6) and the dam`s open-field general activity (PND7) were evaluated. In the second experiment, the maternal pre- and postnatal parameters, the pup`s development, the offspring`s sexual behavior in adulthood, and the pup`s organ weights were assessed. Results: Compared to the control group, the LPS-treated dams presented reduced maternal behavior, decreased general activity, a smaller body weight difference between GD21 and PND1, a greater number of perinatal deaths, and smaller litters. For the male pups, LPS treatment resulted in a decreased body weight on PND2, whereas the anogenital distance and the day of testis descent were not modified. The male sexual behavior was impaired by prenatal LPS. Particularly the number of ejaculating animals was reduced. The testis weight was also lower in the prenatally LPS-treated rats than in the control rats. Conclusion: We propose that prenatal LPS exposure on GD21 acts as an imprinting factor that interferes with the programming of brain sexual determination in offspring. Copyright (C) 2009 S. Karger AG, Basel

Prenatal LPS exposure reduces olfactory perception in neonatal and adult rats

Prenatal lipopolysaccharide (LPS) exposure causes reproductive, behavioral and neurochemical defects in both dams and pups. The present study evaluated male rats prenatally treated with LPS for behavioral and neurological effects related to the olfactory system, which is the main sensorial path in rodents. Pregnant Wistar rats received 100 mu g/kg of LPS intraperitoneally (i.p.) on gestational day (GD) 9.5, and maternal behavior was evaluated. Pups were evaluated for (1) maternal odor preference, (2) aversion to cat odor, (3) monoamine levels and turnover in the olfactory bulb (OB) and (4) protein expression (via immunoblotting) within the OB dopaminergic system and glial cells. Results showed that prenatal LPS exposure impaired maternal preference and cat odor aversion and decreased dopamine (DA) levels in the OB. This dopaminergic impairment may have been due to defects in another brain area given that protein expression of the first enzyme in the DA biosynthetic pathway was unchanged in the OB. Moreover, there was no change in the protein expression of the DA receptors. The fact that the number of astrocytes and microglia was not increased suggests that prenatal LPS did not induce neuroinflammation in the OB. Furthermore, given that maternal care was not impaired, abnormalities in the offspring were not the result of reduced maternal care. (C) 2011 Elsevier Inc. All rights reserved.

Single early prenatal lipopolysaccharide exposure prevents subsequent airway inflammation response in an experimental model of asthma

Aims: There has been emerging interest in the prenatal determinants of respiratory disease. In utero factors have been reported to play a role in airway development, inflammation, and remodeling. Specifically, prenatal exposure to endotoxins might regulate tolerance to allergens later in life. The present study investigated whether prenatal lipopolysaccharide (LPS) administration alters subsequent offspring allergen-induced inflammatory response in adult rats. Main methods: Pregnant Wistar rats were treated with LPS (100 mu g/kg, i.p.) on gestation day 9.5 and their ovariectomized female offspring were sensitized and challenged with OVA later in adulthood. The bronchoalveolar lavage (BAL) fluid, peripheral blood, bone marrow leukocytes and passive cutaneous anaphylaxis were evaluated in these 75-day-old pups. Key findings: OVA sensitized pups of NaCl treated rats showed an increase of leucocytes in BAL after OVA challenge. This increase was attenuated, when mothers were exposed to a single LPS injection early in pregnancy. Thus, LPS prenatal treatment resulted in (1) lower increased total and differential (macrophages, neutrophils, eosinophils and lymphocytes) BAL cellularity count; (2) increased number of total, mononuclear and polymorphonuclear cells in the peripheral blood; and (3) no differences in bone marrow cellularity or passive cutaneous anaphylaxis. Significance: In conclusion, female pups treated prenatally with LPS presented an attenuated response to experimentally-induced asthma. We observed reduced immune cell migration from peripheral blood to the lungs, with no effect on the production of bone marrow cells or antibodies. It was suggested that inflammatory events such as exposure to LPS in early fetal life can attenuate allergic inflammation in the lung, which is a common symptom in asthma. (C) 2011 Elsevier Inc. All rights reserved.