Maternal urinary tract infection alters water maze performance in the offspring Kim Cronise*, Sandra J. Kelly Department of Psychology, University of South Carolina, Columbia, SC 29208, USA Received 15 May 2000; received in revised form 24 January 2001; accepted 8 March 2001 Abstract The effects of maternal urinary tract infection (UTI) or endotoxin exposure on fetal outcome in rats were investigated. Prior to conception, dams of the UTI group were water-deprived and anesthetized. The urinary tract was then catheterized and injected with 0.2 of 1 Â 10 9 Escherichia coli. The endotoxin group was injected with 0.03 mg/kg lipopolysaccharide on the fourth day of gestation and then every third day thereafter. The control groups were treated in the same manner, with the exception that the infection control was not catheterized or injected with E. coli, and the endotoxin control was not exposed to lipopolysaccharide. A nontreated control group was weighed daily. Beginning on postnatal day (PD) 19, offspring were tested daily in a water maze spatial navigation task. The retention latencies (Sessions 7 – 10) revealed deficits in the infection and endotoxin groups. In the rat model, these findings suggest that exposure during gestation to a maternal immune challenge may result in adverse fetal outcome. D 2001 Elsevier Science Inc. All rights reserved. Keywords: Maternal urinary tract infection; Fetal development; Spatial learning; Endotoxin 1. Introduction Changes in endocrine and urinary tract systems during pregnancy increase the risk for developing urinary tract infections (UTIs) significantly [14]. Statistics have dem- onstrated that 2% to 10% of all pregnant women will develop asymptomatic bacteriuria [5]. If left untreated, approximately 30% of these bacteriurics can develop acute pyelonephritis [29]. There is evidence from animal and human data that suggest that these UTIs during pregnancy may be teratogenic to the fetus [5 – 9,14,15,17,19,22,24]. Effects such as prematurity, low birth weight, small for gestational age, and stillbirths after acute cases of UTI have been observed [6,8,15,16,19,24]. Importantly, the evidence also suggests an association between maternal UTIs and insult to the developing fetal brain. Specifically, researchers propose that human infants born to women with UTIs during pregnancy demonstrate poor motor performance at 8 months of age and lowered IQ up to age 7 [16,25]. Although the human correlational data suggest maternal UTIs are related to adverse fetal outcomes, these data are difficult to interpret because of other possible contributing factors [5–9,14,15,17,19,22,24]. Some factors that tend to covary with UTI include maternal age and parity, socio- economic status, quality of pre- and postnatal care, diet, drug use, and smoking [2]. Data from human and/or animal research reveal that each of these factors, individually, are capable of influencing fetal outcome. Abel and Hannigan [1], discuss these factors in terms of permissive influences or conditions that set the stage for a biological milieu, which is then provocative for adverse fetal outcome. It is plausible that a maternal UTI may also be a permissive factor that influen- ces fetal outcome via creating a provocative milieu. There are a number of provocative factors by which a UTI could affect the development of the fetus. First, it may be possible that the very presence of an infecting organism is sufficient to elicit fetal damage due to various metabolic by-products, coloni- zation, or other bacterial activity [7,22]. An example would be a direct effect of bacterial endotoxins. Prenatal exposure to endotoxins in animals has been demonstrated to cause anomalies such as hydroencephaly, leukoencephaly, and abnormal hypothalamic – pituitary axes [10,11,21,23]. How- ever, the behavioral significance of the anomalies has yet to be demonstrated. A second possible provocative factor has 0892-0362/01/$ – see front matter D 2001 Elsevier Science Inc. All rights reserved. PII:S0892-0362(01)00142-8 * Corresponding author. Tel.: +1-803-777-9563; fax: +1-803-777- 9558. E-mail address: cronisek@students.cla.sc.edu (K. Cronise). Neurotoxicology and Teratology 23 (2001) 373– 379