Association between paraben exposure and menstrual cycle in female university students in Japan

Nishihama, Yukiko; Yoshinaga, Jun; Iida, Ayaka; Konishi, Shoko; Imai, Hideki; Yoneyama, Miyuki; Nakajima, Daisuke; Shiraishi, Hiroaki

doi:10.1016/j.reprotox.2016.05.010

Cited by 91 publications

(41 citation statements)

References 22 publications

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“…In humans, increased levels of propylparaben (87.8 – 727 μg/L) were associated with a trend of lower antral follicle counts (estimated mean percent change in antral follicle count −16.3, 95% CI: −30.8, 1.3; p=0.07) (Smith et al 2013). A study of Japanese university students showed that higher urinary estrogen-equivalent total paraben and butyl paraben concentrations were associated with shortened menstrual cycles (total paraben AOR: 0.73, 95% CI: 0.56, 0.96; p=0.027; and butyl paraben AOR: 0.83, 95% CI: 0.70, 0.99; p=0.037) (Nishihama et al 2016). Further, subcutaneous exposure of multiple parabens (6 – 210 mg/kg) increased uterine weight in ovariectomized mice (Lemini et al 2003) and implants containing isobutylparaben (approximately 4.36 mg/L/day) increased dam uterine weights in rats (Kawaguchi et al 2009).…”

Section: Parabensmentioning

confidence: 99%

Exposure to endocrine disruptors during adulthood: consequences for female fertility

Rattan

Zhou

Chiang

et al. 2017

Journal of Endocrinology

258

150

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Endocrine disrupting chemicals are ubiquitous chemicals that exhibit endocrine disrupting properties in both humans and animals. Female reproduction is an important process, which is regulated by hormones and is susceptible to the effects of exposure to endocrine disrupting chemicals. Disruptions in female reproductive functions by endocrine disrupting chemicals may result in subfertility, infertility, improper hormone production, estrous and menstrual cycle abnormalities, anovulation, and early reproductive senescence. This review summarizes the effects of a variety of synthetic endocrine disrupting chemicals during adult life. The chemicals covered in this review are pesticides (organochlorines, organophosphates, carbamates, pyrethroids, and triazines), heavy metals (arsenic, lead, and mercury), diethylstilbesterol, plasticizer alternatives (di-(2-ethylhexyl) phthalate and bisphenol A alternatives), 2,3,7,8-tetrachlorodibenzo-p-dioxin, nonylphenol, polychlorinated biphenyls, triclosan, and parabens. This review focuses on the hypothalamus, pituitary, ovary, and uterus because together they regulate normal female fertility and the onset of reproductive senescence. The literature shows that several endocrine disrupting chemicals have endocrine disrupting abilities in females during adult life, causing fertility abnormalities in both humans and animals.

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Section: Parabensmentioning

confidence: 99%

Exposure to endocrine disruptors during adulthood: consequences for female fertility

Rattan

Zhou

Chiang

et al. 2017

Journal of Endocrinology

258

150

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“…Four studies to date (Table 3), two utilizing women from a fertility clinic [41, 42], one including women from a prospective TTP study [43], and the other among Japanese students [44], have investigated the association between female exposure to parabens and markers of fecundity. Smith and colleagues found a borderline association between increasing tertiles of PP and diminished AFC among 192 women in the EARTH Study, but no relation with ovarian volume and day 3 FSH levels [42].…”

Section: Parabensmentioning

confidence: 99%

“…Nevertheless, the authors’ observed an almost 40% reduction in couple fecundity when female partners had a urinary MP and EP concentration in the highest quartile as compared to the lowest quartile. Nishihama and coauthors found associations between urinary concentrations of BP and the sum of all the measured parabens (BP, PP, MP and EP) and shorter menstrual cycle lengths among 128 Japanese students [44]; however, PP, MP and EP did not have independent effects on menstrual cycle length.…”

Section: Parabensmentioning

confidence: 99%

Female exposure to endocrine disrupting chemicals and fecundity: a review

Mínguez-Alarcón¹,

Gaskins

2017

Current Opinion in Obstetrics &Amp; Gynecology

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Purpose of review Endocrine disrupting chemicals (EDCs) have been known for their ability to interfere with aspects of hormone action resulting in adverse health consequences among animals and humans, however, the effects of EDCs on human fecundity have shown inconsistent findings. This review summarizes the most recent epidemiologic literature from humans on the potential effects of female exposure to non-persistent EDCs, specifically bisphenol A (BPA), phthalates, parabens and triclosan, on fecundity, measured by markers of reproductive hormones, markers of ovulation or ovarian reserve, in vitro fertilization outcomes, and time-to-pregnancy. Recent findings While the epidemiologic literature on this topic is growing, the evidence supporting an association between female urinary concentrations of BPA, phthalates, parabens, and triclosan and fecundity remains unclear. The heterogeneous results could be due to methodological differences in recruitment populations (fertile vs. subfertile), study designs (prospective vs. retrospective), assessment of exposure (including differences in the number and timing of urine samples and differences in the analytical methods used to assess the urinary concentrations), residual confounding due to diet or other lifestyle factors, and co-exposures to other chemicals. Summary At present there is limited evidence to conclude that female exposure to non-persistent EDCs affect fecundity in humans. Further studies focusing on exposure to mixtures of EDCs is needed.

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“…Furthermore, parabens represent one category of suspected EDCs that have been investigated for their potential action on ERα and related hormone signaling pathways [28, 47]. Although paraben compounds are generally considered weak agonists of ERα, they are still being investigated to determine whether current exposures may lead to adverse impacts on human health [24, 27, 95]. For example, an epidemiological study reported a possible association between increased BuP exposure and markers of sperm DNA damage in men [96].…”

Section: Discussionmentioning

confidence: 99%

“…For example, an epidemiological study reported a possible association between increased BuP exposure and markers of sperm DNA damage in men [96]. Another study showed a possible dose-response relationship between higher paraben exposure and shorter self-reported menstrual cycle length among female Japanese university students [95]. In addition, the detection of parabens in numerous human tissues [27, 97–103] and their associations with possible endocrine disruption in humans further demonstrate the toxicological relevance of these compounds as test ligands in our study.…”

Section: Discussionmentioning

confidence: 99%

Homology models of mouse and rat estrogen receptor-α ligand-binding domain created by in silico mutagenesis of a human template: Molecular docking with 17β-estradiol, diethylstilbestrol, and paraben analogs

Gonzalez

Rae

Colacino

et al. 2019

Computational Toxicology

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Crystal structures exist for human, but not rodent, estrogen receptor-α ligand-binding domain (ERα-LBD). Consequently, rodent studies involving binding of compounds to ERα-LBD are limited in their molecular-level interpretation and extrapolation to humans. Because the sequences of rodent and human ERα-LBDs are > 95% identical, we expected their 3D structures and ligand binding to be highly similar. To test this hypothesis, we used the human ERα-LBD structure (PDB 3UUD) as a template to produce rat and mouse homology models. Employing the rodent models and human structure, we generated docking poses of 23 Group A ligands (17ß-estradiol, diethylstilbestrol, and 21 paraben analogs) in AutoDock Vina for interspecies comparisons. Ligand RMSDs (Å) (median, 95% CI) were 0.49 (0.21–1.82) (human-mouse) and 1.19 (0.22–1.82) (human-rat), well below the 2.0–2.5 Å range for equivalent docking poses. Numbers of interspecies ligand-receptor residue contacts were highly similar, with Sorensen Sc (%) = 96.8 (90.0–100) (human-mouse) and 97.7 (89.5–100) (human-rat). Likewise, numbers of interspecies ligand-receptor residue contacts were highly correlated: Pearson r = 0.913 (human-mouse) and 0.925 (human-rat). Numbers of interspecies ligand-receptor atom contacts were even more tightly correlated: r = 0.979 (human-mouse) and 0.986 (human-rat). Pyramid plots of numbers of ligand-receptor atom contacts by residue exhibited high interspecies symmetry and had Spearman rs = 0.977 (human-mouse) and 0.966 (human-rat). Group B ligands included 15 ring-substituted parabens recently shown experimentally to exhibit decreased binding to human ERα and to exert increased antimicrobial activity. Ligand efficiencies calculated from docking ligands into human ERα-LBD were well correlated with those derived from published experimental data (Pearson partial rp = 0.894 and 0.918; Groups A and B, respectively). Overall, the results indicate that our constructed rodent ERα-LBDs interact with ligands in like manner to the human receptor, thus providing a high level of confidence in extrapolations of rodent to human ligand-receptor interactions.

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Association between paraben exposure and menstrual cycle in female university students in Japan

Cited by 91 publications

References 22 publications

Exposure to endocrine disruptors during adulthood: consequences for female fertility

Exposure to endocrine disruptors during adulthood: consequences for female fertility

Female exposure to endocrine disrupting chemicals and fecundity: a review

Homology models of mouse and rat estrogen receptor-α ligand-binding domain created by in silico mutagenesis of a human template: Molecular docking with 17β-estradiol, diethylstilbestrol, and paraben analogs

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