Alterations of maternal Estrogen Levels during Gestation affect the Skeleton of Female Offspring

DES side-effects on bones

Alterations of maternal estrogen levels during gestation affect the skeleton of female offspring
DES side-effects on bones

Estrogens have important effects on bone turnover in both humans and experimental animals models. Moreover, the decreased level of estrogen after menopause appears to be one of the key factors in determining postmenopausal osteoporosis. The presence of estrogen receptor in both osteoblasts and osteoclasts has suggested a direct role of these steroid hormones on bone tissue. Thus, this tissue is now regarded as a specific estrogen target tissue. Exposure to estrogens during various stages of development has been shown to irreversibly influence responsive target organs. We have recently shown that transient developmental neonatal exposure (days 1-5 of life) of female mice to estrogen resulted in an augmented bone density in the adult animals. The aim of the present study was to evaluate whether short-term modification of maternal estrogen levels during pregnancy would induce changes in the skeleton of the developing fetuses and to identify any long-term alterations that may occur. Pregnant mice were injected with varying doses (0.1-100 micrograms/kg maternal BW) of the synthetic estrogen diethylstilbestrol (DES) from day 9-16 of pregnancy. Offspring were weaned at 21 days of age, and effects on bone tissue of the female mice were evaluated in adulthood (6-9 months of age). Prenatal DES treatment(s) did not significantly affect BW. However, a dose-dependent increase in bone mass, both in the trabecular and cortical compartments, was observed in the prenatal DES-exposed female offspring. Furthermore, long bones of DES-exposed females were shorter than controls. Normal skeletal mineralization accompanied these changes in the bone tissue, as shown by a parallel increase in skeletal calcium content. Double tetracycline labeling performed in 6-month-old DES-exposed animals showed an increase in mineral apposition rate in adult DES-exposed mice as compared with untreated control animals, although no significant difference in the circulating estrogen levels was found in animals of this age. Experiments were then performed to evaluate whether perturbation of the estrogen surge at puberty in these diethylstilbestrol (DES)-exposed mice could reverse the observed changes. Femur length was chosen as a marker of potential estrogenic effect. Prepubertal ovariectomy of the prenatally DES-treated animals could only partially reverse the effects observed in the skeleton of the DES-treated animals. Further experiments were performed to evaluate whether these changes could have occurred in utero. CD-1 pregnant female mice were injected with DES (100 micrograms/kg maternal BW) from days 9-15 of gestation. On day 16 of gestation, fetuses were examined and stained by a standard Alizarin Red S and Alcian Blue procedure to visualize calcified and uncalcified skeletal tissue. Estrogen treatment induced an increase in the amount of calcified skeleton as compared with untreated controls and also a decrease in the length of long bones, strongly suggesting a change in both endochondral ossification and endosteal and periosteal bone formation. In summary, these data show, for the first time, that alterations in the maternal estrogenic levels during pregnancy can influence early phases of fetal bone tissue development and subsequently result in permanent changes in the skeleton. Finally, the effect of this short-term estrogen treatment can be seen in the fetal skeleton, suggesting an estrogen-imprinting effect on bone cell-programming in fetal life because treatment effects on bone cell turnover can be observed later in adult life. ”

Abstract, NCBI Endocrinology, May 1996 – Full text here

Related post: Alterations in Estrogen Levels during Development affects the Skeleton: use of an Animal Model, October 1995.

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Endocrine Disruptors permanent effect on Obesity through at least three Generations

Warnings From a Flabby Mouse

Warnings From a Flabby Mouse
Estrogens like DES permanently disrupt the hormonal mechanisms regulating body weight

A new study found that endocrine disruptors cause mice to grow obese and suffer liver disease through at least three generations.

This confirms the 2005 NIEHS Study where DES appears to permanently disrupt the hormonal mechanisms regulating body weight in mice – (see Elizabeth Grossman’s “Chemicals May Play Role in Rise in Obesity“).
The common thread is that the most important time for exposure appears to be in utero and in childhood. Should doctors do more to warn pregnant women about certain chemicals?

Read Warnings From a Flabby Mouse, by Nicholas D. Kristof
The NewYorkTimes, January 2013


  • Transgenerational Inheritance of Increased Fat Depot Size, Stem Cell Reprogramming, and Hepatic Steatosis Elicited by Prenatal Exposure to the Obesogen Tributyltin in Mice,
    EHP1205701, January 2013.
  • Developmental exposure to estrogenic compounds and obesity,
    NIEHS Symposium Proceedings, 10.1002/bdra.20147, June 2005.
DES and Obesity

L’Hypospadias chez les “petits-garçons DES” (3ème Génération) issus de “grands-mères Distilbène”

Les “petits-garçons DES” issus de “grands-mères distilbène” sont 40 à 50 fois plus exposés au risque de malformations du pénis

Une étude montre que les petits-enfants des femmes traitées avec l’hormone de synthèse Distilbène® DES, médicament prescrit aux femmes enceintes jusqu’à la fin des années 70 et sensé prevenir les fausses couches, sont 40 à 50 fois plus exposés au risque de malformations du pénis.

Le Distilbène DES, en savoir plus

Endometriosis Rate estimated to be 80% greater in Women exposed to DiEthylSilbestrol in Utero

Endometriosis: If We Ignore It Will It Go Away?

Endometriosis: If We Ignore It Will It Go Away?Endometriosis occurs when endometrial cells grow where they shouldn’t – in places other than the uterus lining. It is estimated that up to 10% of women, or more, suffer endometriosis. Some studies have recently indicated that molecules from plastic, that break down in heat, can mimic estrogen, and may contribute to hormone problems, such as endometriosis. The rate of endometriosis is estimated to be 80% greater in women exposed to DiEthylStilbestrol in utero.

Read Endometriosis: If We Ignore It Will It Go Away?
by Kymberly Fergusson.

DES and Endometriosis

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The Mammogram I have Not had

Exactly the struggles DES Daughters are experiencing in the UK

Read The Mammogram I Have Not Had by DaphneA brilliant blog post which shows exactly the struggles DES Daughters like me and others are experiencing in the UK when it comes to getting breast screenings

Thanks Daphne! Read The Mammogram I Have Not Had.
All posts tagged Breast Cancer.

DES and Breast Cancer (UK)

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Increased Risks Chart for Diethylstilbestrol-exposed Women (2nd Generation)

Are you a probable DES Daughter?
See this Chart and establish how much Risk you face!

Image courtesy of the National Cancer Institute.

A study of daughters of women given diethylstilbestrol, synthetic estrogen, during pregnancy has found that exposure to the drug while in the womb is associated with many reproductive problems and an increased risk of certain cancers.

DES is definitely no a drug of the past : this chart highlights the increased health risks associated with DES exposure, compared to the risks for women who were not exposed to DES in the womb.

Read Women exposed to Diethylstilbestrol in the Womb face increased Cancer Risk from the NIH/National Cancer Institute,
October 6, 2011.

More DES DiEthylStilbestrol Resources

DES DiEthylStilbestrol Resources (5)

Want to know more about the pregnancy drug DiEthylStilbestrol?

DES-molecule image
New AFSSAPS DES survey and update
DES historical facts, current issues, risks associated with DES exposure, breast cancer risks, post adolescent psychiatric disorders, risks for the 3rd generation, DES pregnancy care.

DES Sons Numbers and Health Concerns
Although less is known about the consequences of diethylstilbestrol exposure in men than in women, important DES health concerns have been identified.

DES Sons Studies
The most common reported health issues in DES sons studies are epididymal cysts, testicular problems, testicular cancer, infertility, psychological and neurological effects.

Gender Identity and DES Exposure
Dr. Dana Beyer radio interview on the significant evidence linking prenatal Diethylstilbestrol DES exposure with gender identity and transsexual development.

Historic DES Breast Cancer Court Cases
Boston Federal Courthouse holds the first DES Breast Cancer court cases on behalf of 53 DES Daughters September 07-23 2011.

More DES DiEthylStilbestrol Resources

DES DiEthylStilbestrol Resources (3)

Want to know more about the pregnancy drug DiEthylStilbestrol?

DES-molecule image
Diethylstilbestrol DES

DES, Guilt, Fear, and other Emotions
Review of the emotions including anger, anxiety, fear, frustration and guilt felt by most diethylstilbestrol DES victims.

DES Activist outside USA
Carol Devine, Founder and Coordinator of DES Action Australia-NSW, highlights the difficulties for a DES activist to access information outside USA.

DES and Breast Cancer Risks
Are DES daughters at higher risk of Breast Cancer? What is the NHS approach in UK and what are the prevention measures?

Wanted: DES Aware Doctors
Please contact your local DES Action Group if you know a sensitive, aware doctor that you would recommend to DES victims.

DES (Diethylstilbestrol) Symposium May 2011
Find Location, Time, Speakers & Programme of May 2011 DES Symposium held in Boston U.S.A.

More DES DiEthylStilbestrol Resources

DES DiEthylStilbestrol Resources (1)

Want to know more about the pregnancy drug DiEthylStilbestrol?

DES-molecule image
Diethylstilbestrol DES
Journal of a DES daughter on Di-Ethyl Stilbestrol® (or diethylstilboestrol in UK). Sources DES action groups, DES exposure, DES pregnancy & DES media information.

DES Exposure
Diethylstilbestrol exposure may have affected three generations (DES mothers, their children and grandchildren). Sources review of DES exposure.

DES Side Effects
Diethylstilbestrol side effects may have affected three generations (DES mothers, their children and grandchildren). Sources review of DES side effects.

DES Pregnancy
Diethylstilbestrol side effects are frightening, but here is a message of hope to all DES daughters living a DES pregnancy.

Distilbene® Drug
Despite warnings to discontinue using DES in pregnancy, Distilbène® continued to be prescribed to pregnant women in France until 1977.

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