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Embryonic Exposure to Low-Dose 17β-Estradiol Decreases Fetal Mass Sex Specifically in Male Mice and Does Not Cause Hypospadias
  1. Sarah D. Blaschko,
  2. Emily J. Willingham,
  3. Laurence S. Baskin
  1. From the Department of Pediatrics, University of California, Irvine School of Medicine (S.D.B.), Irvine, CA; and Department of Urology (E.J.W., L. S.B.), University of California, San Francisco, San Francisco, CA.
  1. This work was supported by National Institutes of Health grant R01DK58105 to L.S.B. All work was performed in strict accordance with protocols approved by the Institutional Animal Care and Use Committee at the University of California, San Francisco.
  2. Address correspondence to: Dr. Laurence S. Baskin, Department of Urology, University of California, San Francisco, 400 Parnassus Avenue, Box 0738, San Francisco, CA 94143; e-mail: lbaskin{at}urology.ucsf.edu.

Abstract

Background Endocrine-disrupting compounds are synthetic and natural compounds in the environment that can alter endocrine-governed developmental processes. Among these are the natural estrogens genistein, a plant isoflavone, and 17β-estradiol (E2), which is present in dietary animal products, such as eggs and meat. In addition, natural and synthetic steroids are administered to beef cattle to promote growth, and low levels of the estrogens can persist in the beef. Most previous work using E2 has involved injection; however, oral administration results in a different suite of hormone products following first-pass metabolism in the liver.

Methods Low doses of E2 were administered orally to pregnant dams to determine embryonic effects. As end points of effects, we examined whether embryonic exposure produced hypospadias, an endocrine-linked abnormality of the male genitalia, and we assessed fetal mass.

Results Male fetuses from the two highest dosage groups were significantly smaller than their control male counterparts, and males from the highest dosage group were also significantly smaller than control females. Control males were significantly larger than all females, and there was no difference in mass among control and treated females. Additionally, the E2 dose was inversely correlated with mass overall. No effect of these doses of E2 on hypospadias was seen.

Conclusions These results indicate a sex-specific fetal effect of low-dose, orally administered E2, which appears to exert androgen-inhibiting effects on mass in males.

Key words
  • 17β-estradiol
  • embryonic
  • mass

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