Transcriptomic changes and potential regulatory mechanism of intrauterine human chorionic gonadotropin co-cultured with peripheral blood mononuclear cells infusion in mice with embryonic implantation dysfunction

This study aimed to explore whether intrauterine infusion of peripheral blood mononuclear cells (PBMCs) could induce favorable transcriptomic changes in the endometrium for embryo implantation and the potential mechanism.

Intrauterine PBMCs perfusion might improve the performance of impaired endometrial receptivity by regulating LIF, SLC15A2, RARRES1, VCAM1, MSC as well as CXCL14, and hCG could enhance the effect of PBMCs. In addition, GR-β, as a transcriptional factor, could regulate the six genes in PBMCs.

Twenty-one mice were randomly divided to five groups, including a normal pregnancy (NP) group, an embryo implantation dysfunction (EID) group, an EID with human chorionic gonadotropin (hCG) group, an EID with PBMCs group, and an EID with hCG co-cultured with PBMCs group. The endometrium in the implantation window from mice were collected and determined by RNA sequencing (RNA-Seq), and the expression of significantly different genes with high degree of coincidence was recommended and validated by quantitative real-time polymerase chain reaction (qRT-PCR).

There were totally 1,366 up-regulated and 1,374 down-regulated genes in the EID mice compared with the normal pregnant mice. We selected (fold change ≥2, P<0.05) and verified the candidate genes associated with embryo implantation, immune response and other reproductive processes in previous reports by qRT-PCR. Leukemia inhibitory factor (LIF), solute carrier family 15 member 2 (SLC15A2), retinoic acid receptor responder 1 (RARRES1), vascular cell adhesion molecule 1 (VCAM1) were down-regulated and musculin (MSC), chemokine (C-X-C motif) ligand 14 (CXCL14) were up-regulated significantly in EID group (P<0.05), and the synergistic effects of hCG were seen. In addition, the expression of glucocorticoid receptor (GR)-β in PBMCs of NP mice was higher than that of EID mice, and up-regulated GR-β in EID mice could significantly increase the expression of LIF, SLC15A2, RARRES1 and VCAM1, and decrease the expression of CXCL14 and MSC, which indicated GR-β might be a transcriptional factor of the six genes above. Conclusions: Intrauterine PBMCs perfusion might improve the performance of impaired endometrial receptivity by regulating LIF, SLC15A2, RARRES1, VCAM1, MSC as well as CXCL14, and hCG could enhance the effect of PBMCs. In addition, GR-β, as a transcriptional factor, could regulate the six genes in PBMCs.