Adult bone marrow-derived progenitors give rise to decidual cells and are essential for implantation and pregnancy maintenance

Bone marrow (BM)-derived progenitor cells (BMDPCs) are known to migrate and give rise to endometrial cells however their functional contribution to implantation and pregnancy are unknown . Here we show that implantation and pregnancy are strong stimuli for BMDPCs recruitment to the uterine decidua where BMDPCs differentiate into functional non-hematopoietic prolactin-producing decidual cells. Transcriptome analysis of implantation sites demonstrated that Hoxa11+/- mice transplanted with WT BM clustered hierarchically more closely with normal WT mice than with control Hoxa11+/- mice, showing normalized expression of numerous implantation-related genes. These findings reveal that BMDPCs have a major non-hematopoietic physiologic contribution to the decidual stroma, and thereby play an essential and previously unproven role in the establishment and maintenance of pregnancy. Overall design: Female Hoxa11 knockout, heterozygotes or wild type mice were given Hoxa11 knockout or wild type bone marrow transplants. After mating, uterine implantation sites were collected and total RNA was extracted on ED 5.5. 14 samples were sequenced by single-end next generation sequencing and differential transcriptome analysis.