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

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.

Keywords: Rat; allogeneic; immunosuppression; offspring; pregnancy; transplantation; uterus.