Induction of hypospadias in a murine model by maternal exposure to synthetic estrogens.
We tested the hypothesis that maternal exposure to synthetic estrogen can cause hypospadias in male offspring and defined the morphological changes in the disrupted urethral seam. Timed pregnant C57/6 mice were exposed to synthetic estrogens. The genital tubercles were examined for the presence of hypospadias using histology, three-dimensional computer reconstruction, and plastic cast injection molds of the urethra. Microscopic serial analysis confirmed the presence of hypospadias, which occurred in approximately 50% of the synthetic-estrogen-treated male fetuses. No effect was seen in the female embryos. Plastic cast injection showed that affected males had a shorter total urethral length and loss of male anatomic features such as the prostatic utricle. Exposure to synthetic estrogens during pregnancy affects the normal development of the urethra in the mouse. We conclude that endocrine disrupters play an important role in genital tubercle anomalies.
Kim
Kun Suk
KS
UCSF Children's Medical Center, Departments of Urology, Anatomy and Pediatrics, University of California, San Francisco, CA 94143, USA.
Torres
Carlos R
CR
Yucel
Selcuk
S
Raimondo
Kamakshi
K
Cunha
Gerald R
GR
Baskin
Laurence S
LS
D000818:Animals; D017931:DNA Primers; D004195:Disease Models, Animal; D004587:Electrophoresis, Agar Gel; D045166:Estradiol Congeners / Q000633:toxicity*; D047628:Estrogen Receptor alpha; D005260:Female; D006652:Histological Techniques; D007021:Hypospadias / Q000139:chemically induced* / Q000473:pathology*; D021621:Imaging, Three-Dimensional; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008810:Mice, Inbred C57BL; D011960:Receptors, Estrogen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D045166:Estradiol Congeners; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen