Translator Disclaimer
3 February 2022 Chemokine C-X-C receptor 4 mediates recruitment of bone marrow-derived nonhematopoietic and immune cells to the pregnant uterus
Yuan-Yuan Fang, Fang Lyu, Nafeesa Abuwala, Aya Tal, Alice Y. Chen, Hugh S. Taylor, Reshef Tal
Author Affiliations +
Abstract

Bone marrow-derived progenitor cells (BMDPCs) are mobilized to the circulation in pregnancy and get recruited to the pregnant decidua where they contribute functionally to decidualization and successful implantation. However, the molecular mechanisms underlying BMDPCs recruitment to the decidua are unknown. CXCL12 ligand and its CXCR4 receptor play crucial roles in the mobilization and homing of stem/progenitor cells to various tissues. To investigate the role of CXCL12–CXCR4 axis in BMDPCs recruitment to decidua, we created transgenic GFP mice harboring CXCR4 gene susceptible to tamoxifen-inducible Cre-mediated ablation. These mice served as BM donors into wild-type C57BL/6 J female recipients using a 5-fluorouracil-based nongonadotoxic submyeloablation to achieve BM-specific CXCR4 knockout (CXCR4KO). Successful CXCR4 ablation was confirmed by RT-PCR and in vitro cell migration assays. Flow cytometry and immunohistochemistry showed a significant increase in GFP+ BM-derived cells (BMDCs) in the implantation site as compared to the nonpregnant uterus of control (2.7-fold) and CXCR4KO (1.8-fold) mice. This increase was uterus-specific and was not observed in other organs. This pregnancy-induced increase occurred in both hematopoietic (CD45+) and nonhematopoietic (CD45–) uterine BMDCs in control mice. In contrast, in CXCR4KO mice there was no increase in nonhematopoietic BMDCs in the pregnant uterus. Moreover, decidual recruitment of myeloid cells but not NK cells was diminished by BM CXCR4 deletion. Immunofluorescence showed the presence of nonhematopoietic GFP+ cells that were negative for CD45 (panleukocyte) and DBA (NK) markers in control but not CXCR4KO decidua. In conclusion, we report that CXCR4 expression in nonhematopoietic BMDPCs is essential for their recruitment to the pregnant decidua.

Summary statement: Expression of CXCR4 receptor in nonhematopoietic bone marrow-derived progenitor cells is essential for their recruitment to the decidua during pregnancy.

Graphical Abstract

img-z2-2_1083.jpg
© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Yuan-Yuan Fang, Fang Lyu, Nafeesa Abuwala, Aya Tal, Alice Y. Chen, Hugh S. Taylor, and Reshef Tal "Chemokine C-X-C receptor 4 mediates recruitment of bone marrow-derived nonhematopoietic and immune cells to the pregnant uterus," Biology of Reproduction 106(6), 1083-1097, (3 February 2022). https://doi.org/10.1093/biolre/ioac029
Received: 16 November 2021; Accepted: 28 January 2022; Published: 3 February 2022
JOURNAL ARTICLE
15 PAGES


Share
SHARE
KEYWORDS
Bone marrow
CXCR4
implantation
pregnancy
stem cells
uterus
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top