Association of angiotensin II and receptors in peri-implantation endometrium with microvessel density and pregnancy outcomes of women with recurrent implantation failure after embryo transfer

Ruofan Qi; Tao Zhang; Yingying Zhang; Jacqueline Pui Wah Chung; Wen-Jui Yang; Chi Chiu Wang

doi:10.3389/fendo.2023.1206326

Association of angiotensin II and receptors in peri-implantation endometrium with microvessel density and pregnancy outcomes of women with recurrent implantation failure after embryo transfer

Front Endocrinol (Lausanne). 2023 Aug 29:14:1206326. doi: 10.3389/fendo.2023.1206326. eCollection 2023.

Authors

Ruofan Qi¹, Tao Zhang¹, Yingying Zhang¹, Jacqueline Pui Wah Chung¹, Wen-Jui Yang^{2

3}, Chi Chiu Wang^{1

4

5

6}

Affiliations

¹ Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
² Department of Infertility and Reproductive Medicine, Taiwan IVF Group Center, Hsinchu, Taiwan.
³ Department of Fertility and Reproductive Medicine, Ton-Yen General Hospital, Hsinchu, Taiwan.
⁴ Reproduction and Development Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
⁵ School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
⁶ Chinese University of Hong Kong -Sichuan University Joint Laboratory in Reproductive Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.

Abstract

Purpose: Investigate whether local angiotensin II (AngII) and its AngII type 1 and 2 receptors (AT1R, AT2R) in the endometrium are different and correlate with microvessel density in women with reproductive failure and pregnancy outcomes.

Methods: Endometrium during the window of implantation from 40 women with recurrent miscarriage (RM) and 40 with recurrent implantation failure (RIF) were compared with 27 fertile women. Peri-implantation endometrium from 54 women prior to euploid embryo transfer were collected and compared in women with successful pregnancy and unsuccessful pregnancy.

Results: Compared with fertile women, expression of AT2R was significantly lower, while AT1R/AT2R expression ratio was significantly higher in the stroma of the RIF group. Endometrium arteriole MVD was significantly lower and negatively correlated with the AT1R/AT2R expression ratio in the stroma of the RIF group. No significant differences and correlations were found in the RM group. Compared with the pregnancy group, expression of AT1R and AT2R were significantly lower in all compartments, but only AT1R/AT2R ratio was significantly higher in the stroma of the non-pregnancy group. Similarly, endometrium arteriole MVD was also significantly lower and negatively correlated with the AT1R/AT2R ratio in the stroma of the non-pregnancy group.

Conclusion: Local renin-angiotensin system is dysregulated in peri-implantation endometrium and associated with abnormal angiogenesis in RIF and poor implantation outcome after embryo transfer.

Keywords: angiogenesis; endometrium; implantation; receptivity; renin angiotensin system.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Abortion, Habitual*
Angiotensin II
Embryo Transfer
Endometrium
Female
Humans
Microvascular Density
Peptide Hormones*
Pregnancy
Pregnancy Outcome

Substances

Angiotensin II
Peptide Hormones

Grants and funding

The study was supported by General Research Fund from Research Grant Council: 14122021 and The Hong Kong Obstetrical and Gynaecological Trust Fund in 2020.