Perinatal Exposure to Perfluorooctane Sulfonate Affects Glucose Metabolism in Adult Offspring

Abstract

Perfluoroalkyl acids (PFAAs) are globally present in the environment and are widely distributed in human populations and wildlife. The chemicals are ubiquitous in human body fluids and have a long serum elimination half-life. The notorious member of PFAAs, perfluorooctane sulfonate (PFOS) is prioritized as a global concerning chemical at the Stockholm Convention in 2009, due to its harmful effects in mammals and aquatic organisms. PFOS is known to affect lipid metabolism in adults and was found to be able to cross human placenta. However the effects of in utero exposure to the susceptibility of metabolic disorders in offspring have not yet been elucidated. In this study, pregnant CD-1 mice (F0) were fed with 0, 0.3 or 3 mg PFOS/kg body weight/day in corn oil by oral gavage daily throughout gestational and lactation periods. We investigated the immediate effects of perinatal exposure to PFOS on glucose metabolism in both maternal and offspring after weaning (PND 21). To determine if the perinatal exposure predisposes the risk for metabolic disorder to the offspring, weaned animals without further PFOS exposure, were fed with either standard or high-fat diet until PND 63. Fasting glucose and insulin levels were measured while HOMA-IR index and glucose AUCs were reported. Our data illustrated the first time the effects of the environmental equivalent dose of PFOS exposure on the disturbance of glucose metabolism in F1 pups and F1 adults at PND 21 and 63, respectively. Although the biological effects of PFOS on the elevated levels of fasting serum glucose and insulin levels were observed in both pups and adults of F1, the phenotypes of insulin resistance and glucose intolerance were only evident in the F1 adults. The effects were exacerbated under HFD, highlighting the synergistic action at postnatal growth on the development of metabolic disorders.

Serum perfluorinated chemicals, glucose homeostasis and the risk of diabetes in working-aged Taiwanese adults

“…In our study, PFOS was significantly associated with a steeper upward post load glucose trajectory and prevalent diabetes. This finding is supported by two animal studies showing developmental PFOS exposure may link to impaired glucose metabolism in adulthood (Lv et al, 2013;Wan et al, 2014). Moreover, the observed potential protective effect of PFOA in our study is consistent with a recent animal study, which demonstrated that PFOA may induce insulin hypersensitivity in mice (Yan et al, 2015).…”

“…Experimental studies has shown the obesity-related metabolic effects of PFASs including endocrine disrupting capacity and differential activation of nuclear receptors especially peroxisome proliferator-activated receptors (PPARs) (White et al, 2011). Recent animal studies also support the potential diabetogenic effect of PFASs (Lv et al, 2013;Wan et al, 2014;Wang et al, 2014). Epidemiologic studies investigating the association between PFASs and diabetes are scarce and the results are not consistent.…”

Embryonic exposures to perfluorooctanesulfonic acid (PFOS) disrupt pancreatic organogenesis in the zebrafish, Danio rerio

“…Detection in both cord blood and amniotic fluid samples demonstrates that PFOS can also cross the placental barrier, indicating an exposure risk to the developing fetus (Inoue et al, 2004; Toft et al, 2016). Numerous studies have associated PFOS exposures with markers for metabolic syndrome and diabetes, such as elevated insulin and cholesterol, insulin resistance, and altered beta cell function (Lin et al, 2009; Lv et al, 2013; Nelson et al, 2010; Wan et al, 2014). However, the pathological consequences of PFOS exposure for the fetal pancreas, as well as the underlying mechanism of PFOS-induced metabolic dysfunction, remain unknown.…”

Longitudinal Associations of Exposure to Perfluoroalkylated Substances in Childhood and Adolescence and Indicators of Adiposity and Glucose Metabolism 6 and 12 Years Later: The European Youth Heart Study

“…Animal studies have suggested that intrauterine and perinatal exposure to PFOS may contribute to impaired glucose tolerance and abnormal lipid homeostasis in adulthood (10,11). In humans, prenatal exposure to PFASs has been considered a catalyst of later weight gain in longitudinal studies (12)(13)(14).…”