Mouse Models Of Hypospadias

Hypospadias is one of the most common congenital abnormalities of the genitalia , seen in about 3 per 1000 male births abroad and 1 per 1000 male births domestic, and the birth rate of hypospadias has increased during the last few decades. Although the etiology of hypospadias is elusive, the environmental estrogens accout for parts. In order to elucidate the mechanism of environmental estrogens of hypospadias and to instruct treatment, it is necessary to establish a mouse model of hypospadias induced by estrogen or antiandrogen.Part one A Mouse Model of Hypospadias Induced by Estradiol BenzoateObjective To establish a mouse model of hypospadias by estradiol benzoate to further studying molecular mechanisms of hypospadias. Method Fifty timed pregnant mouse randomly divided into five groups A, B, C, D, E. Estradiol benzoate was injected subcutaneously(sc) with mixture sesame oil at 0 mg-kg-1-d-1, 0.2 mg-kg-1-d-1, 1 mg-kg-1-d-1, 5 mg-kg-1-d-1 , 25 mg-kg-1-d-1 from GD 12 to 16, respectively. On the day of delivery mortality was recorded. The fetus of two pregnants from each group were anatomied to observe the positions of testes and prostates agenesis on the day of delivery. Urethras and the position of testes were examined on postnatal day 28 . Result Mortality of group A, B, C, D, E was 21.6%, 21.5%, 41.4%, 56.6%, 75% on the day of delivery, respectively. Hypospadias was seen in the group C 3.3%(1/30), D 20% (4/20), E 23% (3/13) and cryptorchidism in the group C 6.6% (2/30), D 30% (6/20), E 61.6% (8/13) on postnatal day 28. Conclusion The experimental model of hypospadias induced by estradiol benzoate ingroup D was more steady considering high mortality of group E. The dose of group D was suitable for establishing mouse model of hypospa-dias.Part two A Mouse Model of Hypospadias Induced byFlutamideObjective To establish a mouse model of hypospadias induced by fluta-mide to further studying molecular mechanisms of hypospadias etiology. Method Eighty timed pregnant mouse randomly divided into four groups A, B, C, D. Flutamide was injected subcutaneously(sc) with mixture sesame oil at 0 mg-kg-1 d-1 25 ing-kg-1-d-1, 50 mg-kg-1 d-1, 100 mg-kg-1-d-1 from GD 12 to 16, respectively. The fetus of two pregnants from each group were anatomied to observe the position of testes and prostates agenesis on the day of delivery. Urethras and the position of testes and prostates agenesis were examined on postnatal day 28. Result Hypospadias were seen in the group A 0%, B 44.2%, C 92.7%, D 100% and cryptorchidism in the group A 0%, B 4.8%, C 23.2%, D 32.4% on postnatal day 28, respectively. Flutamide caused 100% incidence of prostate agenesis in groups C, D and 19.2% in the group B and 100% incidence of female-like anogenital distance in groups B, C, D. Conclusion The experimental model of hypospadias induced by flutamide was more steady and suitable for spread.