Adult bone marrow progenitors become decidual cells and contribute to embryo implantation and pregnancy

Abstract

Decidua is a transient uterine tissue shared by mammals with hemochorial placenta and is essential for pregnancy. The decidua is infiltrated by many immune cells promoting pregnancy. Adult bone marrow (BM)-derived cells (BMDCs) differentiate into rare populations of nonhematopoietic endometrial cells in the uterus. However, whether adult BMDCs become nonhematopoietic decidual cells and contribute functionally to pregnancy is unknown. Here, we show that pregnancy mobilizes mesenchymal stem cells (MSCs) to the circulation and that pregnancy induces considerable adult BMDCs recruitment to decidua, where some differentiate into nonhematopoietic prolactin-expressing decidual cells. To explore the functional importance of nonhematopoietic BMDCs to pregnancy, we used Homeobox a11 (Hoxa11)-deficient mice, having endometrial stromal-specific defects precluding decidualization and successful pregnancy. Hoxa11 expression in BM is restricted to nonhematopoietic cells. BM transplant (BMT) from wild-type (WT) to Hoxa11−/− mice results in stromal expansion, gland formation, and marked decidualization otherwise absent in Hoxa11−/− mice. Moreover, in Hoxa11+/− mice, which have increased pregnancy losses, BMT from WT donors leads to normalized uterine expression of numerous decidualization-related genes and rescue of pregnancy loss. Collectively, these findings reveal that adult BMDCs have a previously unrecognized nonhematopoietic physiologic contribution to decidual stroma, thereby playing important roles in decidualization and pregnancy.

Unique Molecular Features in High-Risk Histology Endometrial Cancers

“…In women undergoing stem cell transplant, endometrial biopsies show donor HLA-type cells [28]. Recently, studies in mice have shown that bone marrow-derived stem cells can repopulate the mouse uterus and allow for fertility in previously subfertile mice [29]. In these experiments, Hoxa11-/- mice are infertile due to defects in decidualization, a form of endometrial stromal differentiation.…”

CXCR4 or CXCR7 antagonists treat endometriosis by reducing bone marrow cell trafficking

“…Further, BM‐derived endothelial progenitor cells (EPCs) also contribute to endometriosis vascularization . We have recently demonstrated a functional role of bone marrow‐derived stem cells in pregnancy …”

“…11,12 We have recently demonstrated a functional role of bone marrow-derived stem cells in pregnancy. 13 In cancer models, signals from the tumour microenvironment systemically stimulate quiescent bone marrow compartments, resulting in the expansion, mobilization and recruitment of BMderived cells 14,15 with a clear role in tumour development. 14,16 C-X-C motif chemokine ligand 12 (CXCL12) is one of the best-characterized chemokines active in mobilization of BM-derived stem cells in cancer and inflammation.…”

Cell-free DNA Methylation and Transcriptomic Signature Prediction of Pregnancies with Adverse Outcomes

“…The bone marrow cells are the main source of all haematopoietic progenitor cells. In addition, they are also a source of nonhematopoietic decidual cells that play a fundamental role during the early phase of placentation [35]. The increment of bone marrow cellular contribution to the maternal cfRNA pool we observed early in pregnancy in GDM subjects may aid in early detection of APOs besides heralding perturbed placentation.…”