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大鼠同种异体子宫移植后的妊娠:围产期结局与生长轨迹

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

作者信息

Díaz-García César, Johannesson Liza, Shao Ruijin, Bilig Håkan, Brännström Mats

机构信息

Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; Fertility Preservation Unit, Women's Health Area, La Fe University Hospital, University of Valencia, Valencia, Spain; Instituto de Investigaciones Sanitarias La Fe, Valencia, Spain.

Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.

出版信息

Fertil Steril. 2014 Dec;102(6):1545-52.e1. doi: 10.1016/j.fertnstert.2014.09.010. Epub 2014 Oct 18.

DOI:10.1016/j.fertnstert.2014.09.010
PMID:25439799
Abstract

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.

SETTING

University hospital.

ANIMAL(S): Lewis rats as uterus donors and Piebald-Virol-Glaxo rats as recipients.

INTERVENTION(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.

RESULT(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.

摘要

目的

研究在大鼠模型中,使用他克莫司进行免疫抑制的同种异体子宫移植能否孕育出产后生长正常的后代。

设计

实验动物研究。

地点

大学医院。

动物

以Lewis大鼠作为子宫供体,花斑-维罗尔-葛兰素大鼠作为受体。

干预措施

动物被分为以下三组之一:同种异体子宫移植,与髂外血管进行端侧吻合,并使用他克莫司进行免疫抑制(UT+Tac;n = 10);假手术并使用他克莫司进行免疫抑制(Sham+Tac;n = 10);或假手术(Sham;n = 10)。随后将这些大鼠与经证实具有生育能力的雄性大鼠交配,若怀孕,则在妊娠第22天进行剖宫产。

主要观察指标

移植物存活率、生育率、围产期死亡率、出生体重、出生后生长轨迹。

结果

对照组(假手术组为70%,假手术+他克莫司组为80%)的妊娠率高于移植组(UT+Tac组为50%),尽管这些差异未达到显著阈值。各组之间存活幼崽数量或新生儿死亡情况无差异。UT+Tac组母亲所生幼崽的出生体重与我们繁殖群体(BC)中的外部对照动物相似:UT+Tac组雄性幼崽6.2±0.2克,UT+Tac组雌性幼崽5.5±0.6克,BC组雄性幼崽5.8±0.2克,BC组雌性幼崽5.2±0.3克;无显著差异。对怀孕动物的子宫和胎盘进行评估发现,UT+Tac组的这两种组织中的血管密度均有所降低,而假手术+他克莫司组未出现这种情况。

结论

在大鼠模型中,同种异体子宫移植及使用他克莫司进行免疫抑制与正常妊娠及围产期结局相容。

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