Intrauterine administration of autologous peripheral blood mononuclear cells regulates the endometrium estrogen and progesterone receptor expression: An RCT

Fattaneh Farifteh; Elham Fazeli; Seyedeh Zeinab Hosseini; Seyedeh Soheila Arefi; Ashraf Moini; Robabeh Taheripanah; Fatemeh Rouhollah; Mohammad Salehi; Ahmad Hosseini; Moncef Benkhalifa

doi:10.18502/ijrm.v21i4.13273

Intrauterine administration of autologous peripheral blood mononuclear cells regulates the endometrium estrogen and progesterone receptor expression: An RCT

Int J Reprod Biomed. 2023 May 8;21(4):343-354. doi: 10.18502/ijrm.v21i4.13273. eCollection 2023 May.

Authors

Fattaneh Farifteh^{1

2}, Elham Fazeli³, Seyedeh Zeinab Hosseini⁴, Seyedeh Soheila Arefi^{2

5}, Ashraf Moini^{6

7

8}, Robabeh Taheripanah⁹, Fatemeh Rouhollah⁴, Mohammad Salehi^{2

10}, Ahmad Hosseini^{2

3}, Moncef Benkhalifa¹¹

Affiliations

¹ Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
² Genetics and In Vitro Assisted Reproductive (GIVAR) Center, Erfan Hospital, Tehran, Iran.
³ Mehr Fertility Research Center , Guilan University of Medical Sciences , Rasht, Iran.
⁴ Department of Cellular and Molecular Sciences, Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
⁵ Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
⁶ Breast Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran.
⁷ Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
⁸ Department of Gynecology and Obstetrics, Arash Women's Hospital, Tehran University of Medical Sciences, Tehran, Iran.
⁹ Infertility and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
¹⁰ Department of Biotechnology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
¹¹ ART and Reproductive Genetics Department and PERITOX Laboratory, CURS, University Hospital and School of Medicine, Picardie University Jules Verne, Amiens Sud, France.

Abstract

Background: Repeated implantation failure (RIF) affects 15% of women of reproductive age. There is a high endometrial expression of both estrogen receptors and progesterone receptors (PRs) during the window of implantation in women with RIF.

Objective: To evaluate the effects of intrauterine administration of human peripheral blood mononuclear cells (PBMC) on estrogen receptor α (ERα) and PRs expression in the endometrium of women with RIF during the implantation window.

Materials and methods: This randomized clinical trial study was conducted on 22 women with RIF history from January 2018 to August 2019 in Erfan hospital, Tehran, Iran. Participantswere divided into 2 groups (PBMC-treated group [n = 11] and control group [n = 11]). Endometrial tissue samples were collected at the implantation window time, during the mid-secretory phase (luteinizing hormone surge +7 days) of each menstrual cycle. The quantitative real-time polymerase chain reaction technique was used to measure the mRNA levels of ERα and PRs isoforms (PR-A and PR-B) in endometrial tissues. Furthermore, the protein expression of ERα and PRs was investigated using immunohistochemical staining.

Results: PBMC treatment significantly decreased the mRNA expression of endometrial ERα and PRs isoforms at the time of the implantation window (p $<$ 0.001). Moreover, the endometrial ERα and PRs protein localization were significantly lower in PBMC-treated women compared with controls (p = 0.01, and p $<$ 0.001 respectively).

Conclusion: The intrauterine administration of PBMC decreased the endometrial ERα and PRs expression during the window of implantation in women with RIF. This local response to PBMC therapy could promote endometrial receptivity and embryo implantation.

Keywords: Estrogen receptors; Progesterone receptors.; Peripheral blood mononuclear cell.