Uterus transplants (UTxs) have been performed worldwide. Overall frequencies have been low, but globally initiated UTx programs are expected to increase clinical implementation. The uterus constitutes a unique immunological environment with specific features of tissue renewal and a receptive endometrium. Decidual immune cells facilitate embryo implantation and placenta development. Although UTx adds to the complexity of immunity during pregnancy and transplantation, the procedure provides a unique clinical and experimental model. We posit that understanding the distinct immunological properties at the interface of the transplanted uterus, the fetus and maternal circulation might provide valuable novel insights while improving outcomes for UTx. Here, we discuss immunological challenges and opportunities of UTx affecting mother, pregnancy and healthy livebirths.
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