Maternal–Fetal Transfer of Domoic Acid in Rats at Two Gestational Time Points

Abstract

Background and objectivesPrenatal exposure to asymptomatic doses of domoic acid (DA) causes learning and memory deficits later in life; therefore, we sought to measure distribution of DA in maternal plasma and brain, prenatal brain, and amniotic fluid 1 hr after exposure, a time frame that normally encompasses acute seizure behavior.MethodsPregnant rats were given a single intravenous dose of DA (0.6 or 1.6 mg/kg body weight) at either gestational day (GD) 13 or GD20, which correspond to the beginning of rat embryo neurogenesis and the last day of gestation, respectively. Using a direct ELISA, dose-dependent levels of DA were detected in each sample matrix tested.ResultsAn average of 6.6 and 14 ng DA/g brain tissue was found in GD13 and GD20 prenatal rats, respectively. Brain concentrations of DA in the GD13 prenates were identical to amniotic fluid levels, consistent with no restriction for DA to enter the GD13 prenatal brain. At GD20 the prenatal brain contained half the concentration of DA in the amniotic fluid, and was approximately half that found in the brain of the dams. After 1 hr, fetal brain and amniotic fluid contained between 1 and 5% of DA found in the maternal circulation. The amniotic fluid levels of DA in this study were also within the same range measured in stranded California sea lions that showed reproductive failure.ConclusionsDA crosses the placenta, enters brain tissue of prenates, and accumulates in the amniotic fluid. Amniotic fluid appears to be a useful fluid to monitor DA exposure.

Exposure of the North Atlantic right whale Eubalaena glacialis to the marine algal biotoxin, domoic acid

“…These animals experienced much higher toxin levels than those estimated herein for E. glacialis. However, DA is actually cleared rapidly in adults but not cleared effectively from the fetal unit (Maucher & Ramsdell 2007), and the fetus is thus considered to be more susceptible to DA poisoning on the basis of exposure during pregnancy. In fact, fetal poisoning was proposed by Ramsdell & Zabka (2008) to have a more prominent effect later in life, manifest as a greater likelihood of developing neurological disease.…”

Intrauterine environment-genome interaction and Children's development (2): Brain structure impairment and behavioral disturbance induced in male mice offspring by a single intraperitoneal administration of domoic acid (DA) to their dams

“…Prenatal exposure of xenobiotic chemicals that interfere with the glutamate recep--ture of the brain which should lead to anomaly of higher brain function that is different from acute neurotoxicity known for such chemicals to induce in adults (Bondy and Campbell, 2005). A marine biotoxin domoic acid (DA) which is structurally related to glutamate, and activates -pionic acid (AMPA) and kinate subtypes of glutamate receptors (Pulido, 2008) is known to cause acute symp-1990), and DA induced acute neurotoxicity in animal Intrauterine environment-genome interaction and Children's development (2): Brain structure impairment and behavioral disturbance induced in male mice offspring by a single intraperitoneal administration of domoic acid (DA) to their dams model (Chandrasekaran et al is also known to cross the placenta, and enters prenatal brain tissue in rats (Maucher and Ramsdell, 2007). Therefore, prenatal exposure of DA may disrupt the neural activities by excessive stimulation of glutamate recep--a transient transplacental DA exposure in utero induced alteration of the neurobehavioral parameters and correin their adulthood.…”

Angler exposure to domoic acid via consumption of contaminated fishes

“…In contrast, experiments with rats have demonstrated that low DA doses can precondition the brain and induce tolerance against higher DA doses in young, but not aged, rats (Kerr et al 2002, Hesp et al 2004. In humans, the most susceptible individuals to low DA doses may include pregnant and nursing women, since experiments with rats showed that (1) low DA doses may be transferred through milk and placenta, and accumulated in the amniotic fluid of pregnant rats and the brain of prenatal rats (Maucher & Ramsdell 2005, 2007; and (2) DA can reach the brain without restriction, causing neurological and behavior effects later in the life for prenatal rats (Dakshinamurti et al 1993, Levin et al 2005, Maucher & Ramsdell 2007. In humans, the elderly (> 65 yr) are most susceptible, since DA is cleared from the plasma through the kidneys (Suzuki & Hierlihy 1993), and old individuals are thought to have reduced ability to eliminate DA through the renal system (Xi et al 1997, Pulido 2008.…”