Establishment of a mouse model of hypospadias induced by estradiol benzoate / 中华男科学杂志

<p><b>OBJECTIVE</b>To establish a mouse model of hypospadias induced by benzoate estradiol to further the studies on the molecular mechanisms of hypospadias.</p><p><b>METHODS</b>A total of pregnant mice were randomly divided into 5 groups, Group A, B, C, D and E, and injected subcutaneously (sc) with estradiol benzoate at the dose of 0, 0.2, 1, 5 and 25 mg x kg(-1) d(-1) respectively from the 12th to the 16th gestational day. The mortality of the newborn mice was recorded and the male neonates of 2 pregnant mice from each group were anatomized to observe the testis position and prostate agenesis on the delivery day. Examinations were made for urethra and cryptorchidism on the 28th postnatal day.</p><p><b>RESULTS</b>The death rates of the neonates in Group A, B, C, D and E were 21.6%, 21.5%, 41.4%, 56. 6% and 75.0%, respectively. Hypospadias was detected in Group C (3.3%, 1/30), D (20.0%, 4/20) and E (23.0%, 3/13), with significant difference between Group D and A (P < 0.05) and E and A (P < 0.05), but not between Group D and E (P > 0.05). Cryptorchidism was found in Group C (6.6%, 2/30) , D (30.0%, 6/20) and E (61.6%, 8/13), with significant difference between Group D and A (P < 0.05) and E and A (P < 0.05) , but not between Group D and E (P >0.05).</p><p><b>CONCLUSION</b>Exposure of pregnant mice to large dose of estradiol benzoate can induce hypospadias and cryptorchidism in their neonates. And the right dose of estradiol benzoate for the establishment of the mouse model of hypospadias should be 5 mg x kg(-1) x d(-1).</p>

Transplantation tolerance mediated by regulatory T cells in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>With potent suppressive effect on responder T cells, CD(4)(+)CD(25)(+) regulatory T (Treg) cells have become the focus of attention only recently and they may play an important role in transplantation tolerance. However, the mechanism of action is not clear. This study was designed to assess the possibility of using CD(4)(+)CD(25)(+) Treg cells to induce transplantation tolerance and to investigate their mechanism of action.</p><p><b>METHODS</b>CD(4)(+)CD(25)(+) Treg cells were isolated using magnetic cell separation techniques. Mixed lymphocyte reactions were used to assess the ability of Treg cells to suppress effector T cells. Before skin transplantation, various numbers of CD(4)(+)CD(25)(+) Treg cells, which have been induced using complex skin antigens from the donor, were injected into the host mice either intraperitoneally [0.5 x 10(5), 1 x 10(5), 2 x 10(5), 3 x 10(5), 4 x 10(5), or 5 x 10(5)] or by injection through the tail vein [5 x 10(3), 1 x 10(4), 2 x 10(4), 5 x 10(4), 1 x 10(5), 2 x 10(5)]. Skin grafts from two different donor types were used to assess whether the induced Treg cells were antigen-specific. The survival time of the allografts were observed. Single photon emission computed tomography was also used to determine the distribution of Treg cells before and after transplantation.</p><p><b>RESULTS</b>Treg cells have suppressive effect on mixed lymphocyte reactions. Grafts survived longer in mice receiving CD(4)(+)CD(25)(+) Treg cell injections than in control mice. There was a significant difference between groups receiving intraperitoneal injection of either 2 x 10(5) or 3 x 10(5) CD(4)(+)CD(25)(+) Treg cells and the control group (P < 0.05, respectively). Better results were achieved when Treg cells were injected via the tail vein than when injected intraperitoneally. The transplantation tolerance induced by CD(4)(+)CD(25)(+) Treg cells was donor-specific. Analysis of the localization of Treg cells revealed that Treg cells mainly migrated from the liver to the allografts and the spleen.</p><p><b>CONCLUSIONS</b>CD(4)(+)CD(25)(+)Treg cells can induce donor-specific transplantation tolerance. Cell-to-cell contact may be the primary mechanism by which Treg cells act on effector T cells.</p>