A Mouse Model Of Hypospadias Induced By Soy Isoflavone And Pathogenesy Of Studying

PART ONE A mouse model of hypospadias induced by soy isoflavoneObject To establish a hypospsdias mouse model by maternal exposure to soy isoflavone during late pregnancy and to further study molecular mechanism of hypospadias.Methods Forty-five pregnancy mouse were randomly divided into five groups,The were injected 0.2ml·d^-1with Sodium Chloride,0.5 mg·kg^-1d^-1 with diethylstilbestrol,100 mg·kg^-1d^-1,300mg·kg^-1d^-1,900 mg·kg^-1d^-1 with soy isoflavone from growth days12 to 17,respectively.At the delivery day mortality was recorded.Urethras was examined at postnatal day 28.Results Mortalities in groupA,B,C,D,E were 2.0%,18%,3.8%,5.4%,10%at the delivery day,respectively.Hypospadias rates were in groups B and E were 28%(11/39),19%(10/52) at postnatal day 28.Compared E with A,CandD have different influence of incidence of hypospadias in mice(P＜0.05).The groups E and B had no distinction.Conclusion Kunming mice can be used to build up successfully hypospadias model if gavage of soy isofiavone for 6d with a dosage of 900 mg·kg^-1d^-1.PART TWO Determination of content of teslen and aquadioi in serum of hypospadias miceObject Determination of content of teslen and aquadiol in serum of hypospadias mice.To investigated the pathogenesy of hypospadias by soy isoflavone induced.Methods To selected ten normal mice,ten non-hypospadias mice with low soy isoflavone,ten non-hypospadias mice with midst soy isoflavone and ten hypospadias mice.Detected the testosterone(T) and estradiol(E2) by radioimmunoassay and compared respectively.Results The contents of T in groups F,G,H,I had significantly distinction(P＜0.05).But the content of E2 had no distinction.Conclusion The content of T had significantly distinction between normal control mice and hypospadias mice.But the content of E2 had no distinction. PART THREE Determination of AR in skin of penis and testis of hypospadias miceObject To study the expression of androgen receptor and its pathogenesy in skin of penis and testis ofhypospadias mice by soy isoflavone induced.Methods Ten normal control mice,ten non-hypospadias mice and ten hypospadias mice by soy isoflavone induced were choose randomly.The expression of androgen receptor was detected by immunohistochemistry in skin of penis and testis of mice.Results The AR content in skin of penis in mice with hypospadias(L) was significantly lower than in normal control mice(J) and non-hypospadias mice(K)(P＜0.05).But there was no significance between J and K.The AR in testis was not significantly difference in 3 groups mice.Conclusion Soy isoflavone induce hypospadias mice which may be caused by decreasing the expression of AR in skin of penis and the combination between androgen and AR.