Association of perfluoroalkyl substances exposure in utero with reproductive hormone levels in cord blood in the Hokkaido Study on Environment and Children's Health

Itoh, Shinji; Araki, Atsuko; Mitsui, Takahiko; Miyashita, Chihiro; Goudarzi, Houman; Sasaki, Seiko; Cho, Kazutoshi; Nakazawa, Hiroyuki; Iwasaki, Yusuke; Shinohara, Nobuo; Nonomura, Katsuya; Kishi, Reiko

doi:10.1016/j.envint.2016.05.011

Cited by 96 publications

(54 citation statements)

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“…In addition, we reported that prenatal exposure to PFOS was inversely associated with progesterone levels in cord blood of male and female infants in the same cohort. In contrast, prenatal PFOA levels were positively associated with cord blood progesterone levels in male and female infants (Itoh et al 2016). Therefore, this may partly explain the negative association of PFOS but not PFOA with glucocorticoids in the present study.…”

Section: Discussionmentioning

confidence: 89%

“…Previously, our group has reported a negative association between prenatal PFOS and progesterone hormone levels of cord blood samples in male and female infants. In addition, PFOS was negatively associated with testosterone/estradiol in male infants, whereas prenatal PFOA exposure was positively associated with progesterone levels in cord blood samples of both sexes (Itoh et al 2016). However, the effects of PFCs on glucocorticoid hormones and androgenic hormones (the main substrates of testosterone and estrogen) are not well understood in humans.…”

Section: Introductionmentioning

confidence: 99%

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The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study

Goudarzi

Araki

Itoh

et al. 2017

Environ Health Perspect

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Background:Perfluorinated chemicals (PFCs) disrupt cholesterol homeostasis. All steroid hormones are derived from cholesterol, and steroid hormones such as glucocorticoids and androgenic hormones mediate several vital physiologic functions. However, the in utero effects of PFCs exposure on the homeostasis of these steroid hormones are not well understood in humans.Objectives:We examined the relationship between prenatal exposure to perfluorooctane sulfonate (PFOS)/perfluorooctanoate (PFOA) and cord blood levels of glucocorticoid and androgenic hormones.Methods:We conducted a hospital-based birth cohort study between July 2002 and October 2005 in Sapporo, Japan (n = 514). In total, 185 mother–infant pairs were included in the present study. Prenatal PFOS and PFOA levels in maternal serum samples were measured using liquid chromatography–tandem mass spectrometry (LC-MS-MS). Cord blood levels of glucocorticoid (cortisol and cortisone) and androgenic hormones [dehydroepiandrosterone (DHEA) and androstenedione] were also measured in the same way.Results:We found a dose–response relationship of prenatal PFOS, but not PFOA, exposure with glucocorticoid levels after adjusting for potential confounders. Cortisol and cortisone concentrations were –23.98-ng/mL (95% CI: –0.47.12, –11.99; p for trend = 0.006) and –63.21-ng/mL (95% CI: –132.56, –26.72; p for trend < 0.001) lower, respectively, in infants with prenatal PFOS exposure in the fourth quartile compared with those in the first quartile. The highest quartile of prenatal PFOS exposure was positively associated with a 1.33-ng/mL higher DHEA level compared with the lowest quartile (95% CI: 0.17, 1.82; p for trend = 0.017), whereas PFOA showed a negative association with DHEA levels (quartile 4 vs. quartile 1: –1.23 ng/mL, 95% CI: –1.72, –0.25; p for trend = 0.004). We observed no significant association between PFCs and androstenedione levels.Conclusions:Our results indicate that prenatal exposure to PFCs is significantly associated with glucocorticoid and DHEA levels in cord blood.Citation:Goudarzi H, Araki A, Itoh S, Sasaki S, Miyashita C, Mitsui T, Nakazawa H, Nonomura K, Kishi R. 2017. The association of prenatal exposure to perfluorinated chemicals with glucocorticoid and androgenic hormones in cord blood samples: the Hokkaido Study. Environ Health Perspect 125:111–118; http://dx.doi.org/10.1289/EHP142

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study

Goudarzi

Araki

Itoh

et al. 2017

Environ Health Perspect

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“…Regarding metabolic effects, strong inverse associations between maternal PFOS with triglycerides, essential fatty acids and omega 3 and 6 fatty acids during pregnancy have been described [33]. Studies also found that prenatal exposure to PFASs is associated with glucocorticoids (cortisol and cortisone) and reproductive hormone (DHEA, progesterone, estradiol and testosterone) levels [97•, 98], suggesting that PFASs may reprogram the endocrine system and shift steroidogenesis. Mechanisms potentially involved in the neurobehavioral effects of PFASs exposures include influences on calcium homeostasis, protein kinase C, synaptic plasticity, cellular differentiation or via the thyroid hormone system [17, 24, 99].…”

Section: Discussionmentioning

confidence: 99%

Developmental Exposures to Perfluoroalkyl Substances (PFASs): An Update of Associated Health Outcomes

Liew

Goudarzi

Oulhote

2018

Curr Envir Health Rpt

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182

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PFASs are persistent organic pollutants that have been widely produced and used in a range of commercial products since the 1950s. Human exposures to PFASs are nearly ubiquitous globally, but studies that addressed potential health effects of PFASs have only begun to accumulate in recent years. Animal studies suggest adverse effects resulting from developmental encompasses prenatal exposures to PFASs. In humans, the developing fetus is exposed to PFASs via active or passive placenta transfer, while newborns might be exposed via breastfeeding or PFAS in the home environment. Overall, epidemiological findings are consistent and suggest possible associations with fetal and postnatal growth and immune function, while the findings on neurodevelopmental endpoints to date are rather inconclusive. Methodological challenges and future directions for PFASs-focused research are discussed.

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“…However, epidemiologic evidence does not support a causal association between PFOS exposure and cancer risk in humans 5 . Nonetheless, in utero exposure to PFOS adversely affect the fetal synthesis and secretion of reproductive hormones (e.g., testosterone, estradiol, and inhibin B) in humans 6 . Since the half-life of PFOS and its related compound PFOA (perfluorooctanoic acid) is relatively long, at 5.4-yr and 3.8-yr, respectively 7, 8 , even low-dose exposure to PFOS and its related compounds can accumulate in the body over an extended period of time.…”

Section: Introductionmentioning

confidence: 99%

Perfluorooctanesulfonate (PFOS)-induced Sertoli cell injury through a disruption of F-actin and microtubule organization is mediated by Akt1/2

Gao

Chen

Xiao

et al. 2017

Sci Rep

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PFOS (perfluorooctanesulfonate, or perfluorooctane sulfonic acid) is an anthropogenic fluorosurfactant widely used in consumer products. While its use in Europe, Canada and the U.S. has been banned due to its human toxicity, it continues to be used in China and other developing countries as a global pollutant. Herein, using an in vitro model of Sertoli cell blood-testis barrier (BTB), PFOS was found to induce Sertoli cell injury by perturbing actin cytoskeleton through changes in the spatial expression of actin regulatory proteins. Specifically, PFOS caused mis-localization of Arp3 (actin-related protein 3, a branched actin polymerization protein) and palladin (an actin bundling protein). These disruptive changes thus led to a dis-organization of F-actin across Sertoli cell cytosol, causing truncation of actin microfilament, thereby failing to support the Sertoli cell morphology and adhesion protein complexes (e.g., occludin-ZO-1, CAR-ZO-1, and N-cadherin-ß-catenin), through a down-regulation of p-Akt1-S473 and p-Akt2-S474. The use of SC79, an Akt1/2 activator, was found to block the PFOS-induced Sertoli cell injury by rescuing the PFOS-induced F-actin dis-organization. These findings thus illustrate PFOS exerts its disruptive effects on Sertoli cell function downstream through Akt1/2. As such, PFOS-induced male reproductive dysfunction can possibly be managed through an intervention on Akt1/2 expression.

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Association of perfluoroalkyl substances exposure in utero with reproductive hormone levels in cord blood in the Hokkaido Study on Environment and Children's Health

Abstract: These results suggest that the fetal synthesis and secretion of reproductive hormones may be affected by in utero exposure to measurable levels of PFOS and PFOA.

Cited by 96 publications

References 54 publications

The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study

The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study

Developmental Exposures to Perfluoroalkyl Substances (PFASs): An Update of Associated Health Outcomes

Perfluorooctanesulfonate (PFOS)-induced Sertoli cell injury through a disruption of F-actin and microtubule organization is mediated by Akt1/2

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