Endocrine Disrupting Chemicals and Behavior

Special issue of Hormones and Behavior, Volume 101, Pages 1-148, May 2018

The peer-reviewed journal Hormones and Behavior, Volume 101, Pages 1-148 (May 2018), raises concern about how many of the 90,000+ chemicals in use today may disrupt our most basic endocrine systems with significant consequences for neurodevelopment, neurophysiology, healthy brain aging, and behavior.

Several articles address bisphenol A :

About PDBEs, triclosan, and other replacement chemicals :

Other studies included in this special issue address behavioral effects of voluntary taken pharmaceuticals, including birth control pills, and pain medications.

About DES and the BRAIN :

All species are exposed to EDCs and at risk for adverse neurodevelopmental outcomes

Behavioral and molecular analyses of olfaction-mediated avoidance responses of Rana (Lithobates) catesbeiana tadpoles: Sensitivity to thyroid hormones, estrogen, and treated municipal wastewater effluent

2018 Study Highlights

  • Olfaction is critical in tadpoles for predator avoidance and food location.
  • Thyroid hormones (THs) change olfactory tissues dramatically during metamorphosis.
  • T3 & municipal wastewater effluent, but not T4 or E2, disrupt avoidance behavior.
  • Thra and thibz mRNAs are significantly higher in T3 versus T4 olfactory epithelium.
  • Further bioindicator candidates are needed to link to adverse behavior outcomes.

Abstract

Olfaction is critical for survival, facilitating predator avoidance and food location. The nature of the olfactory system changes during amphibian metamorphosis as the aquatic herbivorous tadpole transitions to a terrestrial, carnivorous frog. Metamorphosis is principally dependent on the action of thyroid hormones (THs), l-thyroxine (T4) and 3,5,3′-triiodothyronine (T3), yet little is known about their influence on olfaction during this phase of postembryonic development.

We exposed Taylor Kollros stage I-XIII Rana (Lithobates) catesbeiana tadpoles to physiological concentrations of T4, T3, or 17-beta-estradiol (E2) for 48 h and evaluated a predator cue avoidance response.

The avoidance response in T3-exposed tadpoles was abolished while T4- or E2-exposed tadpoles were unaffected compared to control tadpoles. qPCR analyses on classic TH-response gene transcripts (thra, thrb, and thibz) in the olfactory epithelium demonstrated that, while both THs produced molecular responses, T3 elicited greater responses than T4. Municipal wastewater feed stock was spiked with a defined pharmaceutical and personal care product (PPCP) cocktail and treated with an anaerobic membrane bioreactor (AnMBR). Despite substantially reduced PPCP levels, exposure to this effluent abolished avoidance behavior relative to AnMBR effluent whose feed stock was spiked with vehicle. Thibz transcript levels increased upon exposure to either effluent indicating TH mimic activity.

The present work is the first to demonstrate differential TH responsiveness of the frog tadpole olfactory system with both behavioral and molecular alterations. A systems-based analysis is warranted to further elucidate the mechanism of action on the olfactory epithelium and identify further molecular bioindicators linked to behavioral response disruption.

Fetal Origin of Adult Disease

Abstract from “Environmental Exposures and Adverse Pregnancy Outcomes: A Review of the Science”

During the last two decades, chronic disease has replaced infectious disease as the major focus of public health concern. The top 4 leading causes of death in the United States are chronic diseases. There remains much unknown about the etiology of many chronic conditions, which in most cases is probably multifactorial. Studies from the 1990s found that effects on the fetal environment, such as through poor or inadequate nutrition, can result in an increased risk of adult onset of chronic conditions, such as coronary heart disease. This has been called the fetal origins hypothesis (also known as the Barker theory), which proposes that external influences on the fetal environment can increase the risk of later disease in adulthood.

Diethylstilbestrol (DES)—a synthetic estrogen given to US women between 1938 and 1971 to prevent pregnancy complications illustrates the fetal origins of later in life disease. In utero DES exposure left mature female offspring at increased risk of clear cell adenocarcinoma of the vagina and cervix, breast cancer, structural reproductive tract anomalies, an increased infertility rate, and poor pregnancy outcomes, while male offspring have an increased incidence of genital abnormalities and a possibly increased risk of prostate and testicular cancer. These observed human effects have been confirmed in numerous animal models, which have also predicted changes later found in DES-exposed humans, such as increased incidence of uterine fibroids, oviductal malformations, and second generational effects such as increased menstrual irregularities and possibly ovarian cancer in DES granddaughters and increased hypospadias in DES grandsons.

Diethylstilbestrol shows the adverse effects of fetal exposures to synthetic chemicals may not be apparent at birth or even for many years afterward, and that continued monitoring of this cohort of exposed children and grandchildren is necessary to inform potential effects of prenatal exposures to other contaminants.

Reference. Image credit Hush Naidoo.

DES DiEthylStilbestrol Resources

Less plastic use help decrease harmful chemicals in the body

The ReThink Plastic Pilot Study Community Report, 2018

A new pilot study has shown that women who reduce their exposure to plastic see a decrease in estrogen-mimicking chemicals in their bodies within a month.

The chemicals used in the manufacture of many plastics are known to mimic estrogen activity. There is strong scientific evidence linking these “environmental estrogens” to breast cancer. The ReThink Plastic study was designed to reduce exposure to these chemicals using simple, practical behavior change and to build a coalition of plastic use reduction by spreading the study messages. This approach could result in broad benefits by effectively reducing exposure to harmful chemicals in plastic and thus protecting against breast cancer and protecting the environment against plastic pollution.

Specifically, the objectives of the study were to:

  1. Inform participants about the harmful effects of chemicals that are in plastic
  2. Teach participants simple ways to reduce the use of plastic in order to reduce the potential for harmful health effects
  3. Ask participants to spread the message to other friends and family
  4. Evaluate the effectiveness of the study:
    • Examine changes in “plastic use” behavior before and after the study
    • Examine changes in estrogenic activity before and after the study in a small sub-study of post-menopausal women.

Reference.

Staying with the Trouble : Making Kin in the Chthulucene

Donna J. Haraway’s poetic guide to finding connection in a time of crisis, 2016

Description

In the midst of spiraling ecological devastation, multispecies feminist theorist Donna J. Haraway offers provocative new ways to reconfigure our relations to the earth and all its inhabitants. She eschews referring to our current epoch as the Anthropocene, preferring to conceptualize it as what she calls the Chthulucene, as it more aptly and fully describes our epoch as one in which the human and nonhuman are inextricably linked in tentacular practices. The Chthulucene, Haraway explains, requires sym-poiesis, or making-with, rather than auto-poiesis, or self-making. Learning to stay with the trouble of living and dying together on a damaged earth will prove more conducive to the kind of thinking that would provide the means to building more livable futures. Theoretically and methodologically driven by the signifier SF—string figures, science fact, science fiction, speculative feminism, speculative fabulation, so far—Staying with the Trouble further cements Haraway’s reputation as one of the most daring and original thinkers of our time.

Awash in Urine,” chapter 5, begins with personal and intimate relations, luxuriating in the consequences of following estrogens that connect an aging woman and her elder dog, specifically, me and my companion and research associate Cayenne. Before the threads of the string figure have been tracked far, remembering their cyborg littermates, woman and dog find themselves in histories of veterinary research, Big Pharma, horse farming for estrogen, zoos, DES feminist activism, interrelated animal rights and women’s health actions, and much more. Intensely inhabiting specific bodies and places as the means to cultivate the capacity to respond to worldly urgencies with each other is the core theme.

More Information

  • Introduction and customer reviews on amazon and goodreads.
  • Donna Haraway lectures at the San Francisco Art Institute, April 25, 2017.
  • Chapter 5 Awash in Urine DES and Premarin in Multispecies Response-ability is lightly revised from Women’s Studies Quarterly 40, nos. 3/4 (spring/summer 2012): 301 – 16.
DES DiEthylStilbestrol Resources

Sex Hormones and Related Compounds, Including Hormonal Contraceptives

ResearchGate, Side Effects of Drugs Annual, July 2017

Abstract

This is a review of publications from January 2016 to December 2016 on sex hormones and related compounds. This chapter covers estrogens (diethylstilbestrol, estradiol and derivatives), progestins (drospirenone, levonorgestrel, medroxyprogesterone, ulipristal), hormone replacement therapy (combination estrogen and progestin, estrogen only, tibolone, oral preparations and topical preparations), hormonal contraceptives (oral, non-oral, combination and progestin only), in vitro fertilization agents, triptorelin (gonadotropin-releasing hormone agonist), anastrozole (aromatase inhibitor) testosterone, anabolic steroids and androgen deprivation therapy.

Request the full-text on ResearchGate.

DES DiEthylStilbestrol Resources

The key role of androgen in male sex maintenance

Blockage of androgen and administration of estrogen induce transdifferentiation of testis into ovary

2017 Study Abstract

Induction of sex reversal of XY fish has been restricted to the sex undifferentiated period.

In the present study, differentiated XY tilapia were treated with trilostane (TR), metopirone (MN) and glycyrrhetinic acid (GA) (inhibitor of 3β-HSD, Cyp11b2 and 11β-HSD, respectively) alone or in combination with 17β-estradiol (E2) from 30 to 90 dah (days after hatching). At 180 dah, E2 alone resulted in 8.3%, and TR, MN and GA alone resulted in no secondary sex reversal (SSR), whereas TR + E2, MN + E2 and GA + E2 resulted in 88.3, 60.0 and 46.7% of SSR, respectively.

This sex reversal could be rescued by simultaneous administration of 11-ketotestosterone (11-KT). Compared with the control XY fish, decreased serum 11-KT and increased E2 level were detected in SSR fish. Immunohistochemistry analyses revealed that Cyp19a1a, Cyp11b2 and Dmrt1 were expressed in the gonads of GA + E2, MN + E2 and TR + E2 SSR XY fish at 90 dah, but only Cyp19a1a was expressed at 180 dah. When the treatment was applied from 60 to 120 dah, TR + E2 resulted in 3.3% of SSR, MN + E2 and GA + E2 resulted in no SSR.

These results demonstrated that once 11-KT was synthesized, it could antagonize E2-induced male-to-female SSR, which could be abolished by simultaneous treatment with the inhibitor of steroidogenic enzymes. The upper the enzyme was located in the steroidogenic pathway, the higher SSR rate was achieved when it was inhibited as some of the precursors, such as androstenedione, testosterone and 5α-dihydrotestosterone, could act as androgens. These results highlight the key role of androgen in male sex maintenance.

Image credit Rusty Clark.

Perinatal Exposure to DES Increases the Susceptibility to Develop Mammary Gland Lesions after Estrogen Replacement Therapy

Hormones and Cancer, April 2017, Volume 8, Issue 2, pp 78–89

2017 Study Abstract

The development of the mammary gland is a hormone-regulated event.

Several factors can dysregulate its growth and make the gland more susceptible to cellular transformation.

Among these factors, perinatal exposure to xenoestrogens and hormone replacement therapy has been associated with increased risk of developing breast cancer.

Perinatal Exposure to Bisphenol A or Diethylstilbestrol Increases the Susceptibility to Develop Mammary Gland Lesions After Estrogen Replacement Therapy in Middle-Aged Rats, US National Library of Medicine National Institutes of Health, Hormones and Cancer, April 2017, Volume 8, Issue 2, pp 78–89, NCBI PubMed PMID: 28078498, 2017 Apr 8.

Here, we assessed the effects induced by estrogen replacement therapy (ERT) in ovariectomized (OVX) middle-aged rats and whether perinatal exposure to diethylstilbestrol (DES) or bisphenol A (BPA) modified these effects in the mammary gland.

Pregnant rats were orally exposed to vehicle, 5 μg DES/kg/day, or 0.5 or 50 μg BPA/kg/day from gestational day 9 until weaning. Then, 12-month-old offspring were OVX and treated with 17β-estradiol for 3 months.

Morphological changes and the percentage of epithelial cells that proliferated or expressed estrogen receptor alpha (ESR1) and progesterone receptor (PR) were analyzed in mammary gland samples of 15-month-old animals.

ERT induced lobuloalveolar hyperplasia and ductal cysts in the mammary gland of middle-aged rats, associated with a higher proliferation index of epithelial cells.

Perinatal exposure to DES followed by ERT increased the number of cysts and induced the formation of fibroadenoma and ductal carcinoma in situ, without modifying the expression of ESR1 or PR.

Also, after 3 months of ERT, BPA-exposed rats had a higher incidence of ductal hyperplasia and atypical lobular hyperplasia than animals under ERT alone.

In conclusion, perinatal exposure to xenoestrogens increases the susceptibility of the mammary gland to develop cysts and hyperplastic lesions when confronted with ERT later in life.

More DES DiEthylStilbestrol Resources

Emerging, priority contaminants with endocrine active potentials in sediments, fish from the River Po, Italy

High levels of endocrine-disrupting chemicals found in sediments and fish from the Italian River Po and its Lambro tributary

Researchers have recommended that fish from some sections of the River Po and the River Lambro, one of the Italian River Po tributaries, should not be eaten due to high levels of some endocrine-disrupting chemicals in the river sediments and fish. This recommendation is based on an extensive update regarding pollution levels of such substances in the rivers.

Abstract

There is a substantial lack of information on most priority pollutants, related contamination trends, and (eco)toxicological risks for the major Italian watercourse, the River Po. Targeting substances of various uses and origins, this study provides the first systematic data for the River Po on a wide set of priority and emerging chemicals, all characterized by endocrine-active potentials.

Flame retardants, natural and synthetic hormones, surfactants, personal care products, legacy pollutants, and other chemicals have been investigated in sediments from the River Po and its tributary, the River Lambro, as well as in four fish species from the final section of the main river. With few exceptions, all chemicals investigated could be tracked in the sediments of the main Italian river for tens or hundreds of kilometres downstream from the Lambro tributary.

Nevertheless, the results indicate that most of these contaminants, i.e., TBBPA, TCBPA, TBBPA-bis, DBDPE, HBCD, BPA, OP, TCS, TCC, AHTN, HHCB, and DDT, individually pose a negligible risk to the River Po. In contrast, PBDE, PCB, natural and synthetic estrogens, and to a much lower extent NP, were found at levels of concern either to aquatic life or human health. Adverse biological effects and prohibition of fish consumption deserve research attention and management initiatives, also considering the transport of contaminated sediments to transitional and coastal environments of the Italian river.

More Information
  • Emerging and priority contaminants with endocrine active potentials in sediments and fish from the River Po (Italy), US National Library of Medicine National Institutes of Health, Environmental science and pollution research international, NCBI PubMed PMID: 25956513, 2015 Sep.
  • High levels of endocrine-disrupting chemicals found in sediments and fish from the Italian River Po and its Lambro tributary, Science for Environment Policy, January 2016.
  • Fishing Po image credit Edizonn.

What does Estrogen do?

Why is estrogen important and what can go wrong with estrogen levels?