Exposure to Perfluorooctane Sulfonate during Pregnancy in Rat and Mouse. I: Maternal and Prenatal Evaluations

Abstract

The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. PFOS is an environmentally persistent compound used as a surfactant and occurs as a degradation product of both perfluorooctane sulfonyl fluoride and substituted perfluorooctane sulfonamido components found in many commercial and consumer applications. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestational day (GD) 2 to GD 20; CD-1 mice were similarly treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 17. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). Maternal weight gain, food and water consumption, and serum chemistry were monitored. Rats were euthanized on GD 21 and mice on GD 18. PFOS levels in maternal serum and in maternal and fetal livers were determined. Maternal weight gains in both species were suppressed by PFOS in a dose-dependent manner, likely attributed to reduced food and water intake. Serum PFOS levels increased with dosage, and liver levels were approximately fourfold higher than serum. Serum thyroxine (T4) and triiodothyronine (T3) in the PFOS-treated rat dams were significantly reduced as early as one week after chemical exposure, although no feedback response of thyroid-stimulating hormone (TSH) was observed. A similar pattern of reduction in T4 was also seen in the pregnant mice. Maternal serum triglycerides were significantly reduced, particularly in the high-dose groups, although cholesterol levels were not affected. In the mouse dams, PFOS produced a marked enlargement of the liver at 10 mg/kg and higher dosages. In the rat fetuses, PFOS was detected in the liver but at levels nearly half of those in the maternal counterparts, regardless of administered doses. In both rodent species, PFOS did not alter the numbers of implantations or live fetuses at term, although small deficits in fetal weight were noted in the rat. A host of birth defects, including cleft palate, anasarca, ventricular septal defect, and enlargement of the right atrium, were seen in both rats and mice, primarily in the 10 and 20 mg/kg dosage groups, respectively. Our results demonstrate both maternal and developmental toxicity of PFOS in the rat and mouse.

Developmental toxicity and alteration of gene expression in zebrafish embryos exposed to PFOS

“…Possible explanations for the elevation of hhex and pax8 expressions may be related to the promotion of the growth of the thyroid primordium to compensate for changes in egg TH levels. Lau et al (2003) and Thibodeaux et al (2003) reported reductions in total and/or free serum thyroid hormones (T3 and/or T4) in PFOS-treated rats and mice. Little information is available of the effects of toxicants on thyroid genes or hormones during fish embryo development.…”

Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine‐related genes in vitro and in vivo

“…Exposure to PFOS caused a reduction in serum T4 and T3 in rats and mice [18], and a decrease in serum T3 and estradiol levels in monkeys [27]. However, the mechanism of thyroid disruption still needs to be explored.…”

“…Plasma androgens and estrogens were also altered in PFOS-treated fathead minnows [17]. Serum thyroxine (T4) and triiodothyronine (T3) were reduced by PFCs in animal studies [18,19]. A recent study on the general adult population in the United States has suggested that higher concentrations of serum PFOS are associated with thyroid disease [20].…”

Hyperthyroidism impairs pancreatic beta cell adaptations to late pregnancy and maternal liporegulation in the rat

“…This dose and period of T 3 treatment were selected on the basis of previous studies that demonstrated T 3 -induced changes in metabolic function and gene expression, together with cardiac hypertrophy (results not shown). Although not measured in this series of experiments, the dosage and period of treatment typically generate serum T 3 concentrations of 15-20 nmol/l [29] compared with normal T 3 concentrations of about 1.5 nmol/l [20,30,31]. We elected to administer this treatment specifically during late pregnancy to avoid the potential effect of hyperthyroidism in modulating the expansion of beta cell mass that typically occurs during mid-pregnancy in response to the development of maternal insulin resistance, and because adiposetissue lipid metabolism is geared towards lipolysis rather than lipogenesis during late pregnancy.…”