Sex Steroid Hormone Levels and Reproductive Development of Eight-Year-Old Children following In Utero and Environmental Exposure to Phthalates

Su, Pen Hua; Chen, Jia Yuh; Lin, Ching Yi; Chen, Hsiao Yen; Liao, Pao Chi; Ying, Tsung Ho; Wang, Shu Li

doi:10.1371/journal.pone.0102788

Cited by 25 publications

(31 citation statements)

References 26 publications

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“…Much less is known about phthalates in relation to estradiol and progesterone activity in humans. A study of Taiwanese girls found that serum MEHP and MBzP levels were positively associated with serum progesterone (Su et al, 2014). In a study of pregnant women in Puerto Rico, MEP concentrations were inversely associated with progesterone across pregnancy (Johns et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Toxicoanthropology: Phthalate exposure in relation to market access in a remote forager-horticulturalist population

Sobolewski

Weiss

Martin

et al. 2017

International Journal of Hygiene and Environmental Health

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Phthalates are a class of plasticizing chemicals produced in high volume and widely found in consumer products. Evidence suggests that phthalates may have non-monotonic effects on reproductive hormone activity. With exposure to phthalates virtually ubiquitous among industrialized populations, identifying unexposed and/or minimally exposed human populations is essential for understanding the effects of low level exposures. Our primary objective was to quantify urinary phthalate metabolite concentrations in the Tsimane’, a remote population of Bolivian forager-horticulturalists. Our secondary objectives were to determine if phthalate metabolite concentrations vary in relation to access to market goods; and to explore relationships between phthalate and reproductive hormone metabolite concentrations. Given that phthalate exposure is of particular concern during fetal development, we focused on reproductive age women in the current analyses. Phthalate metabolites were assayed in urine samples from 59 naturally cycling, reproductive age Tsimane’ women. Market access was assessed as: (1) distance from residence to the largest nearby town (San Borja, Bolivia) and (2) Spanish fluency. Urinary reproductive hormone metabolite concentrations were quantified using enzyme immunoassays. We fit linear models to examine: (1) predictors of phthalate exposure; and (2) relationships between urinary phthalate and reproductive hormone metabolite concentrations. Eight phthalate metabolites were detectable in at least 75% of samples. Median concentrations were up to an order of magnitude lower than industrialized populations. Proximity to San Borja and Spanish fluency were strong predictors of exposure. In exploratory analyses, the sum of the di-2-ethylhexyl phthalate metabolites (ΣDEHP) and Mono-isobutyl phthalate (MiBP) were significantly associated with altered concentrations of urinary reproductive hormone metabolites. Remote, subsistence populations, like the Tsimane’, offer a unique window into the health effects of endocrine active compounds because: (1) exposures are low and likely to be first generation; (2) a natural fertility lifestyle allows for exploration of reproductive effects; and (3) ever-increasing globalization will result in increasing exposure in the next decade.

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Section: Discussionmentioning

confidence: 99%

Toxicoanthropology: Phthalate exposure in relation to market access in a remote forager-horticulturalist population

Sobolewski

Weiss

Martin

et al. 2017

International Journal of Hygiene and Environmental Health

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“…Conversely, in utero exposure to MEP and MBzP was associated with increased testosterone levels in girls at ages 8–13 years from the Mexico City birth cohort ( 176 ). Urinary levels of MEHP and MBzP in 8-year-old girls from Taiwan were also positively associated with increased serum progesterone levels and urinary levels of MBzP and MBP were positively associated with increased serum FSH levels ( 177 ).…”

Section: Effects Of Phthalates On Steroidogenesismentioning

confidence: 99%

The Effects of Phthalates on the Ovary

2015

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Phthalates are commonly used as plasticizers in the manufacturing of flexible polyvinyl chloride products. Large production volumes of phthalates and their widespread use in common consumer, medical, building, and personal care products lead to ubiquitous human exposure via oral ingestion, inhalation, and dermal contact. Recently, several phthalates have been classified as reproductive toxicants and endocrine-disrupting chemicals based on their ability to interfere with normal reproductive function and hormone signaling. Therefore, exposure to phthalates represents a public health concern. Currently, the effects of phthalates on male reproduction are better understood than the effects on female reproduction. This is of concern because women are often exposed to higher levels of phthalates than men through their extensive use of personal care and cosmetic products. In the female, a primary regulator of reproductive and endocrine function is the ovary. Specifically, the ovary is responsible for folliculogenesis, the proper maturation of gametes for fertilization, and steroidogenesis, and the synthesis of necessary sex steroid hormones. Any defect in the regulation of these processes can cause complications for reproductive and non-reproductive health. For instance, phthalate-induced defects in folliculogenesis and steroidogenesis can cause infertility, premature ovarian failure, and non-reproductive disorders. Presently, there is a paucity of knowledge on the effects of phthalates on normal ovarian function; however, recent work has established the ovary as a target of phthalate toxicity. This review summarizes what is currently known about the effects of phthalates on the ovary and the mechanisms by which phthalates exert ovarian toxicity, with a particular focus on the effects on folliculogenesis and steroidogenesis. Further, this review outlines future directions, including the necessity of examining the effects of phthalates at doses that mimic human exposure.

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“…Phthalate diester is reported to have anti-androgenic and weak estrogenic effects. 8 , 9 , 10 , 11 , 12 , 13 Small children may be particularly prone to exposure because of frequent hand-to-mouth activity and increased phthalate exposure dose per kilogram of body weight due to small body size. Swan and colleagues found that boys born to mothers with increased urinary levels of phthalate metabolites had reduced anogenital distance.…”

Section: Introductionmentioning

confidence: 99%

“… 16 , 17 A previous study of older children showed that di-n-butyl phthalate (DnBP) is negatively associated with adrenal androgen levels in boys. 16 For girls, increased urinary phthalate levels are associated with delayed pubarche 9 , 13 , 18 ; however, evidence on the effects of phthalates on thelarche is less conclusive. 19 , 20 , 21…”

Section: Introductionmentioning

confidence: 99%

Prenatal and childhood exposure to phthalate diesters and sex steroid hormones in 2-, 5-, 8-, and 11-year-old children: A pilot study of the Taiwan Maternal and Infant Cohort Study

Wen¹,

Sie²,

Su³

et al. 2017

Journal of Epidemiology

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BackgroundPhthalate diesters are commonly used and have been well established as environmental endocrine disruptors. However, few studies have examined their effects on sex steroid hormones in children. We followed children over time to examine the association between pre- and post-natal phthalate exposure and sex steroid hormone levels at 2, 5, 8, and 11 years of age.MethodsWe recruited 430 pregnant women from central Taiwan from 2000 to 2001 and assessed their children at birth, 2, 5, 8, and 11 years of age. We studies children with at least one measurement for both phthalate and hormone levels during each any of the follow-up time point (n = 193). Estradiol, free testosterone, testosterone, and progesterone were measured from venous blood. Three monoesters of di-2-ethylhexyl phthalate (DEHP), mono-benzyl phthalate, mono-n-butyl phthalate, mono-ethyl phthalate, and mono-methyl phthalate were measured in maternal urine collected during the 3rd trimester and child urine collected at each follow-up point. The sum of mono-2-ethylhexyl phthalate (∑MEHP) was calculated by summing the concentrations of the three DEHP monoesters. Generalized estimating equation regression analysis with repeated measures was used to estimate associations between phthalate metabolites and hormone levels.ResultsAfter adjustment for potential confounders, maternal ∑MEHP level was associated with decreased levels of progesterone in girls (β = −0.309 p = 0.001). The child ∑MEHP concentration was associated with decreased levels of progesterone for girls (β = −0.194, p = 0.003) and with decreased levels of free testosterone for boys (β = −0.124, p = 0.004).ConclusionsEarly-life DEHP exposure may alter sex steroid hormones of children over time, which may pose potential reproductive health risks.

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Sex Steroid Hormone Levels and Reproductive Development of Eight-Year-Old Children following In Utero and Environmental Exposure to Phthalates

Cited by 25 publications

References 26 publications

Toxicoanthropology: Phthalate exposure in relation to market access in a remote forager-horticulturalist population

Toxicoanthropology: Phthalate exposure in relation to market access in a remote forager-horticulturalist population

The Effects of Phthalates on the Ovary

Prenatal and childhood exposure to phthalate diesters and sex steroid hormones in 2-, 5-, 8-, and 11-year-old children: A pilot study of the Taiwan Maternal and Infant Cohort Study

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