Pregnancy after allogeneic uterus transplantation in the rat: perinatal outcome and growth trajectory

Pregnancy after allogeneic uterus transplantation in the rat: perinatal outcome and growth trajectory
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DOI:
10.1016/j.fertnstert.2014.09.010
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发表时间:
2014-12-01
影响因子:
6.7
通讯作者:
Brannstrom, Mats
Brannstrom, Mats
中科院分区:
医学2区
文献类型:
--
作者:
Diaz-Garcia, Cesar;Johannesson, Liza;Brannstrom, Mats

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目的:为了研究在大鼠模型中,用他克莫司免疫抑制的同种异体子宫移植物是否可以怀孕,从而产生具有正常出生后生长的后代。设计:实验动物研究。设置:大学医院。动物:刘易斯大鼠作为子宫供体,Piebald-Virol-Glaxo大鼠作为受体。干预:将动物分配到以下三组之一:同种异体子宫移植与髂外血管端侧吻合并用他克莫司免疫抑制(UT+Tac; n = 10);假手术并用他克莫司免疫抑制(Sham+Tac; n = 10);或假手术(Sham; n = 10)。随后将大鼠引入具有已证实生育力的雄性大鼠,并且在导致妊娠的情况下,在妊娠第22天进行剖腹产。主要结果测量:移植物活力、生育率、围产期死亡、出生体重、出生后出生轨迹。对照组(70%Sham和80%Sham +Tac)的妊娠率高于移植组(50%UT +Tac),尽管这些差异未达到显著性阈值。两组之间的存活幼仔数量或新生儿死亡数量无差异。UT+Tac母鼠出生的幼崽出生体重与我们繁殖群(BC)的外部对照动物相似:UT+Tac雄性6.2 +/- 0.2 g,UT+Tac雌性5.5 +/- 0.6 g,BC雄性5.8 +/- 0.2 g,BC雌性5.2 +/- 0.3 g; n.s.妊娠动物的子宫和胎盘的评价显示,在UT+Tac组中,两种组织中的血管密度略有降低,而在Sham+Tac组中未观察到。结论:同种异体子宫移植和他克莫司免疫抑制与大鼠模型中的正常妊娠和围产期结局相容。(C)2014年美国生殖医学会。
Objective: To investigate whether allogeneic uterine grafts in a rat model, with tacrolimus immunosuppression, can harbor pregnancies that result in offspring with normal postnatal growth.Design: Experimental animal study.Settingg: University hospital.Animals(s): Lewis rats as uterus donors and Piebald-Virol-Glaxo rats as recipients.Intrvention(s): Animals were allocated to one of the following three groups: allogeneic uterus transplantation with end-to-side anastomosis to the external iliac vessels and immunosuppression with tacrolimus (UT+Tac; n = 10); sham surgery and immunosuppression with tacrolimus (Sham+Tac; n = 10); or sham surgery (Sham; n = 10). The rats were subsequently introduced to male rats with proven fertility and in the event of resulting pregnancy cesarean sections were performed on day 22 of pregnancy.Main outcome measure(s): Graft viability, fertility rate, perinatal death, birth weight, postnatal birth trajectory.Results(s): Pregnancy rate was higher in the control groups (70% Sham and 80% Sham+Tac) than in the transplanted group (50% UT+Tac), although these differences did not reach the significance threshold. There were no differences between groups regarding number of living pups or neonatal deaths. Pups born from UT+Tac mothers had birth weights similar to external control animals from our breeding colony (BC): UT+Tac males 6.2 +/- 0.2 g, UT+Tac females 5.5 +/- 0.6 g, BC males 5.8 +/- 0.2 g, BC females 5.2 +/- 0.3 g; n.s. Evaluation of uteri and placentas of pregnant animals revealed a somewhat reduced vascular density in both tissues in the UT+Tac group, and that was not seen in the Sham+Tac group.Conclusion(s): Allogeneic uterus transplantation and immunosuppression with tacrolimus is compatible with normal pregnancy and perinatal outcome in a rat model. (C)2014 by American Society for Reproductive Medicine.