The seminal vesicle of prenatally DES-exposed male mice acquired two key characteristics of female tissues
Previous studies from our laboratory on the feminization of the male mouse reproductive tract after prenatal exposure to Diethylstilbestrol (DES) showed that the mRNA for the major estrogen-inducible uterine secretory protein, lactoferrin (LF), was constitutively expressed in the seminal vesicle of male mice exposed prenatally to DES, but not in the seminal vesicle of control mice. After castration, treatment with 17 beta-estradiol (20 micrograms/kg.day) for 3 days induced the LF mRNA in the seminal vesicle of both control and prenatally DES-exposed mice; however, the levels in DES-treated tissues were approximately 6-fold higher than those in control tissue. This report describes the presence of LF in seminal vesicle tissues and secretions of prenatally DES-exposed mice, as determined by immunohistochemistry and Western blot analysis. Further, these data are correlated with immunolocalization of the estrogen receptor in the seminal vesicle tissue. We conclude that the seminal vesicle of prenatally DES-exposed male mice has acquired two key characteristics of female tissues, namely LF production/regulation and estrogen receptor localization/distribution similar to that in uterine tissues.
Female gene expression in the seminal vesicle of mice after prenatal exposure to diethylstilbestrol, NCBI, PMID: 2707167, 1989 May;124(5):2568-76.
Pharmaceutical companies in 2008 alone spent nearly $800 million on sales representatives making visits to health care professionals for antipsychotics and antidepressants
Pharmaceutical companies wooed academic leaders, ghostwrote articles, suppressed damaging health data and lavished doctors with gifts to make prescribing powerful psychotropic drugs to children a blockbuster profit center, a trail of lawsuits over the past two decades shows.
$13 billion paid
Off-label uses pushed
Read Drug firms have used dangerous tactics to drive sales to treat kids, The Denver Post Investigations, ci_25561024, 04/14/2014
Certain endocrine disruptors in household products affect human sperm function and impact fertility
Direct action of endocrine disruptors on human sperm
A plethora of endocrine-disrupting chemicals (EDCs) – present in food, textiles, drugs, household, and personal-care products such as plastic bottles, plastic toys, soap, sunscreens, toothpaste and cosmetics – interfere with human sperm function in a way that may have a negative impact on fertilization.
The German – Danish recent research suggests that endocrine disruptors may contribute to widespread fertility problems in the Western world in a way that has not been recognized until now.
Sources and press releases:
A novel import route for an N‐anchor mitochondrial outer membrane protein aided by the TIM23 complex, EMBO Reports, embr.201338142, 29.04.2014
Endocrine disruptors impair human sperm function, EMBO News, research-news-2014, 12 May 2014
Chemicals in soap can cause male infertility, claim scientists, The Independent, 9353159, 12 May 2014
Sperms’ swimming and navigational skills disrupted by common chemicals, TheGuardian, science/2014/may/12, 12 May 2014
Toothpaste, sunscreen chemicals ‘interfere with sperm function’, MedicalNewsToday, articles/276700, 12 May 2014
DiEthylStilbestrol studies – DES can induce neoplastic cell transformation, mutagenesis, irreversible binding to DNA and protein and unscheduled DNA synthesis
1985 Study Abstract
The site and specificity of the tissue response to a toxicant are of central importance; it is in this area of Diethylstilbestrol (DES) toxicity that the estrogen receptor would appear to play its primary role. Compilation of the various sites of DES toxicity in humans and experimental animals indicates that lesions appear predominantly in estrogen responsive target tissues suggesting that the presence of the estrogen receptor in such target tissues may help govern the tissue specificity of the toxic insult. DES and many of its oxidative metabolites interact with high affinity with the estrogen receptor. Such an interaction may be responsible for localizing DES to target tissues. Autoradiographic and biochemical studies have supported the localization of radiolabeled DES in susceptible tissues. The intracellular mechanism of receptor binding of DES and certain metabolites could then result in mobilization of these compounds to the nucleus. Experimental evidence has shown that DES and a number of its metabolites are able to translocate receptor to the nucleus of uterine cells. Such an action by the receptor results in an increased probability of potential chemical interactions with the genome. The actual induction of a chemical lesion in the target cell may, at this point, proceed by non-receptor mediated mechanisms. For example, studies using in vitro cell culture systems which contain no estrogen receptors have shown that DES can induce neoplastic cell transformation, mutagenesis, irreversible binding to DNA and protein and unscheduled DNA synthesis. These results raise the possibility that a part of DES toxicity may follow pharmacologic principles established for chemical carcinogens. Following induction of the molecular lesion, the role of the receptor continues in this process by mediating increased protein synthesis and mitogenesis in responsive target tissues which ultimately permits a more extensive expression of the toxic effects. It has been demonstrated that DES is a potent mitogen in vivo in both uterine and pituitary tissues, subsequently, the lesion will perpetuate itself through this receptor mediated biological response. This is particularly important since a number of DES induced reproductive tract tumors are expressed only after additional estrogen exposure. While other tumors have been shown to be estrogen sensitive and will regress without continued estrogen stimulation. Therefore, it should be considered that the presence of the estrogen receptor and the estrogen receptor mediated biological responsiveness of a particular tissue are most important in explaining the specificity of DES toxicity.
The role of the estrogen receptor in diethylstilbestrol toxicity, NCBI, PMID: 3913404, Arch Toxicol Suppl. 1985;8:33-42.