title: Comparative effects of neonatal diethylstilbestrol on external genitalia development in adult males of two mouse strains with differential estrogen sensitivity.
abstract: The effect of neonatal exposure to diethylstilbestrol (DES), a potent synthetic estrogen, was examined to evaluate whether the CD-1 (estrogen insensitive, outbred) and C57 (estrogen sensitive, inbred) mouse strains differ in their response to estrogen disruption of male ExG differentiation. CD-1 and C57BL/6 litters were injected with sesame oil or DES (200 ng/g/5 μl in sesame oil vehicle) every other day from birth to day 10. Animals were sacrificed at the following time points: birth, 5, 10 and 60 days postnatal. Neonatally DES-treated mice from both strains had many ExG abnormalities that included the following: (a) severe truncation of the prepuce and glans penis, (b) an abnormal urethral meatus, (c) ventral tethering of the penis, (d) reduced os penis length and glans width, (e) impaired differentiation of cartilage, (f) absence of urethral flaps, and (g) impaired differentiation of erectile bodies. Adverse effects of DES correlated with the expression of estrogen receptors within the affected tissues. While the effects of DES were similar in the more estrogen-sensitive C57BL/6 mice versus the less estrogen-sensitive CD-1 mice, the severity of DES effects was consistently greater in C57BL/6 mice. We suggest that many of the effects of DES, including the induction of hypospadias, are due to impaired growth and tissue fusion events during development.
authors.affiliation: Division of Pediatric Urology, University of California, San Francisco, CA 94143, USA.
authors.forename: Phitsanu
authors.initials: P
authors.lastname: Mahawong
authors.affiliation: Division of Pediatric Urology, University of California, San Francisco, CA 94143, USA.
authors.forename: Adriane
authors.initials: A
authors.lastname: Sinclair
authors.affiliation: Division of Pediatric Urology, University of California, San Francisco, CA 94143, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Pediatric Urology, University of California, San Francisco, CA 94143, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Schlomer
authors.affiliation: Division of Pediatric Urology, University of California, San Francisco, CA 94143, USA.
authors.forename: Esequiel
authors.initials: E
authors.lastname: Rodriguez
authors.affiliation: Division of Pediatric Urology, University of California, San Francisco, CA 94143, USA.
authors.forename: Max M
authors.initials: MM
authors.lastname: Ferretti
authors.affiliation: Division of Pediatric Urology, University of California, San Francisco, CA 94143, USA.
authors.forename: Baomai
authors.initials: B
authors.lastname: Liu
authors.affiliation: Division of Pediatric Urology, University of California, San Francisco, CA 94143, USA.
authors.forename: Laurence S
authors.initials: LS
authors.lastname: Baskin
authors.affiliation: Division of Pediatric Urology, University of California, San Francisco, CA 94143, USA. Electronic address: cunhag@urology.ucsf.edu.
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Cunha
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D004054:Diethylstilbestrol / Q000633:toxicity*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005837:Genitalia, Male / Q000002:abnormalities* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D004054:Diethylstilbestrol
keywords: Diethylstilbestrol; Hypospadias; Mouse; Neonatal; Penis; Prepuce; Urethra