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Updated: Mar 17, 2026

Author Spotlight: Advancing Therapeutic Strategies for Improving Pregnancy Rates by Analyzing Embryo-Endometrium Interactions
Published on: June 21, 2024
[Uterine macrophages affect embryo implantation via regulating vascular endothelial growth factor A in mice]
1Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.E-mail: iriswong2013@163.com.
Objective:
To investigate the role of endometrial macrophages in embryo implantation and in regulating the expression of vascular endothelial growth factor A (VEGFA) in mouse endometrium during the peri-implantation period.
Method:
At D3.5 (D0.5 defined as the morning when a vaginal plug was observed), pregnant mice were divided randomly into experimental group, control group and blank group. In the experimental group, the mice were subjected to intrauterine injection of clodronate liposomes on the left side of uterus to eliminate the macrophages, and PBS liposomes on the right side. PBS liposomes and PBS were administered in the control and blank groups, respectively. The uterine tissues were collected on D5.5 and stained with trypan blue to show the implantation sites. Flow cytometry was performed to examine the percentage of F4/80(+) CD11b(+) macrophages macrophages in the uterus. F4/80(+) macrophage population within the endometrium and ovary and changes in VEGFA expression at the implantation and non-implantation sites were examined using immunohistochemistry.
Results:
Endometrial F4/80(+) CD11b(+) macrophages macrophages were significantly reduced by 74% following intrauterine injection of clodronate liposomes (P<0.05). The number of macrophages in the ovaries showed no significant difference among the 3 groups. In the experimental group, the left side of the uterine showed imcomplete cavity closure with a lower number of implantation site than the right side (2.20∓1.81 vs 5.10∓1.91, P<0.05). VEGFA expression at the implantation site were significantly decreased in the endometrium on the left side with macrophage suppression as compared with that on the right side (P<0.05).
Conclusion:
Endometrial macrophages appear to modulate uterine receptivity by regulating the expression of VEGFA to affect embryo implantation, suggesting the important role of macrophages in embryo implantation.
Insights
Endometrial macrophages are crucial for embryo implantation. Depleting these macrophages reduces implantation success and vascular endothelial growth factor A (VEGFA) expression in mice.
Area of Science:
- Reproductive Biology
- Immunology
- Cell Biology
Background:
- Endometrial macrophages play a critical role in establishing pregnancy.
- Vascular Endothelial Growth Factor A (VEGFA) is vital for angiogenesis and implantation.
Purpose of the Study:
- To investigate the role of endometrial macrophages in mouse embryo implantation.
- To determine if endometrial macrophages regulate VEGFA expression during peri-implantation.
Main Methods:
- Pregnant mice underwent intrauterine clodronate liposome injection to deplete macrophages.
- Uterine tissues were analyzed for macrophage populations (F4/80(+) CD11b(+)) and VEGFA expression via flow cytometry and immunohistochemistry.
- Implantation sites were identified using trypan blue staining.
Main Results:
- Clodronate treatment significantly reduced endometrial macrophages by 74%.
- Macrophage depletion led to incomplete uterine cavity closure and fewer implantation sites.
- VEGFA expression was significantly decreased in macrophage-suppressed areas.
Conclusions:
- Endometrial macrophages modulate uterine receptivity for embryo implantation.
- Macrophages regulate VEGFA expression, impacting implantation success.
- These findings highlight the essential role of macrophages in successful embryo implantation.

