Prenatal Exposure to Perfluorooctanoate and Risk of Overweight at 20 Years of Age: A Prospective Cohort Study

Abstract

Background: Perfluoroalkyl acids are persistent compounds used in various industrial -applications. Of these compounds, perfluorooctanoate (PFOA) is currently detected in humans worldwide. A recent study on low-dose developmental exposure to PFOA in mice reported increased weight and elevated biomarkers of adiposity in postpubertal female offspring.Objective: We examined whether the findings of increased weight in postpubertal female mice could be replicated in humans.Methods: A prospective cohort of 665 Danish pregnant women was recruited in 1988–1989 with offspring follow-up at 20 years. PFOA was measured in serum from gestational week 30. Offspring body mass index (BMI) and waist circumference were recorded at follow-up (n = 665), and biomarkers of adiposity were quantified in a subset (n = 422) of participants.Results: After adjusting for covariates, including maternal pre-pregnancy BMI, smoking, education, and birth weight, in utero exposure to PFOA was positively associated with anthropometry at 20 years in female but not male offspring. Adjusted relative risks comparing the highest with lowest quartile (median: 5.8 vs. 2.3 ng/mL) of maternal PFOA concentration were 3.1 [95% confidence interval (CI): 1.4, 6.9] for overweight or obese (BMI ≥ 25 kg/m2) and 3.0 (95% CI: 1.3, 6.8) for waist circumference > 88 cm among female offspring. This corresponded to estimated increases of 1.6 kg/m2 (95% CI: 0.6, 2.6) and 4.3 cm (95% CI: 1.4, 7.3) in average BMI and waist circumference, respectively. In addition, maternal PFOA concentrations were positively associated with serum insulin and leptin levels and inversely associated with adiponectin levels in female offspring. Similar associations were observed for males, although point estimates were less precise because of fewer observations. Maternal perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (PFOSA), and perfluorononanoate (PFNA) concentrations were not independently associated with offspring anthropometry at 20 years.Conclusions: Our findings on the effects of low-dose developmental exposures to PFOA are in line with experimental results suggesting obesogenic effects in female offspring at 20 years of age.

In utero exposure to perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) did not increase body weight or intestinal tumorigenesis in multiple intestinal neoplasia (Min/+) mice

“…Exposure of CD-1 mice on GD1-17 to 0.01, 0.1 and 3.0 mg/kg PFOA significantly increased body weight, and 0.01 and 0.1 mg/kg affected serum insulin and leptin levels in female offspring (Hines et al, 2009). Associations between maternal PFOA, but not PFOS, serum concentration and overweight/obesity and waist circumference in their daughters, and with serum insulin and leptin levels, were also reported in a prospective cohort study (Halldorsson et al, 2012). Thus both animal and human data indicate that PFOA may be obesogenic.…”

Chemical and non-chemical stressors affecting childhood obesity: a systematic scoping review

“…While this mix of chemical and non-chemical stressors is more indicative of real-world exposures, these studies examined chemical exposure only in utero or from cord blood-not continuously through the follow-up years. 158,[177][178][179] Finding cumulative, multiplicative, and possibly antagonistic effects among the myriad stressors is daunting, but it is important whether we want to explore the argument that multiple stressors are at play in childhood obesity. It is important for researchers to obtain accurate and complete measurements to fill the data gaps so that we can better understand the onset of obesity and potential opportunities to evaluate interventions relevant to childspecific environments.…”

Perfluorooctanoic acid binds to peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation in 3T3-L1 adipocytes

“…8) Moreover, recent studies have indicated that PFOA influences the risk of obesity, as an obesogen, in mice and humans. 9,10) Obesogens are defined functionally as chemicals that promote obesity by increasing the number of fat cells or the storage of fat into existing fat cells. 11) Tributyltin chloride and tetrabromobisphenol A (a halogenated analog of bisphenol A) are representative obesogens that act as agonistic ligands of peroxisome proliferatoractivated receptor γ (PPAR γ), which is a transcription factor that plays a central role in adipocyte differentiation, lipid biosynthesis, and lipid storage.…”

“…11) Tributyltin chloride and tetrabromobisphenol A (a halogenated analog of bisphenol A) are representative obesogens that act as agonistic ligands of peroxisome proliferatoractivated receptor γ (PPAR γ), which is a transcription factor that plays a central role in adipocyte differentiation, lipid biosynthesis, and lipid storage. 12,13) Although PFOA has been reported to exhibit obesogenic properties such as an increased risk for obesity and body weight (BW) gain, 9,10) these mechanisms remain unclear, as there have been relatively few studies on the effects of PFOA on adipocytes and PPAR γ.…”

“…A previous study revealed that prenatal exposure to PFOA increases the risk of obesity after reaching adult age in mice as well as humans. 9,10) Thus, exposure to PFOA during the developmental period could increase the risk of weight gain, possibly by promoting adipocyte differentiation through the activation of PPAR γ. However, PFOA is also a ligand for PPAR α, and the affinity of PFOA for PPAR α is greater than Notes: (A) Lipid droplets after Oil red O staining, (B) GPDH activity, and (C) TG content at day 8.…”