In-utero DES exposure and cardiac structure/function alteration

Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny

Abstract

Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs.

Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart.

Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0μg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5-14.5. At 3 months, male progeny were left sedentary or were swim trained for 4 weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart.

Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny, article/pii/S0041008X12004607, 1 January 2013.

Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged.

We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males.

More DES DiEthylStilbestrol Resources

2 thoughts on “In-utero DES exposure and cardiac structure/function alteration”

  1. Is there any medical testing in development that may indicate exposure to DES? I’ve have most every known affliction seen in DES people without 100% proof I was given it during gestation. I have the intersex fetal development issues that caused ovarian type cancer. I even had some of the largest teratoma ever removed at the mayo clinic. Not only were the teratoma huge but also extremely well developed, with limbs, bones, eyes, and orgain parts. Of course in a non viable life form. In addition I had heart issues, the gender dysphoria and everything else you can imagine. Oh one more thing I felt pregnant my whole adult life. Go figure. It has become very clear to me that some endocrine disrupter chemical cause atleast in part caused my issues.
    I would really would love some information on tests that could be done while I’m alive. Just point me in the right direction for more research. Thank you

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