Receptivity markers in endometrial mesenchymal stem cells of recurrent implantation failure and non‐recurrent implantation failure women: A pilot study

Abstract

Aim Endometrial mesenchymal stem cells (eMSC) have a vital role in regeneration of endometrium during menstrual cycles. Since it has been suggested that (eMSC) likely play a role in uterine receptivity and establishment of pregnancy, we aimed to evaluate the expression levels of five most known receptivity markers‐Integrin (ITG) β1, Rac1, HoxA11, ITGβ3 and Noggin‐in eMSC of recurrent implantation failure (RIF) and non‐RIF women. Methods Human eMSC were isolated from menstrual blood (MB) of RIF and non‐RIF women. The isolated eMSC characterized based on their morphological and behavioral characteristics, expression of MSC‐specific surface CD markers and their capacity of differentiation into osteocytes and adipocytes. The expression levels of the five mentioned receptivity markers were analyzed with real time reverse transcription polymerase chain reaction. Results Our findings revealed that RIF and non‐RIF eMSC expressed all tested genes at different levels. ITGb1 expression in RIF eMSC was lower than its expression in non‐RIF cells. On the other hand, all the other markers were expressed at higher levels in RIF eMSC than in non‐RIF cells although only HOXA11 and ITG β3 showed statistically significant (P < 0.05) higher expression levels. Conclusion This pilot study on determination of the expression levels of uterine receptivity markers in eMSC interestingly indicated that RIF and non‐RIF eMSC were different regarding the expression of these markers. Future studies using these findings can brighten up more the role of eMSC in the endometrium receptivity and establishment of pregnancy.

Management of Resistant Endometrium in Cases of Recurrent Implantation Failure Using Endometrial Mesenchymal Stem Cells as an Innovative Regenerative Therapy-A Short Communication

“…Thus concluding that in this particular pilot study on determination of the expression levels of uterine receptivity markers in eMSC interestingly pointed that RIF and non-RIF eMSC were different regarding the expression of these markers. Future studies using these findings can brighten up more the role of eMSC in the endometrium receptivity and establishment of pregnancy [43].…”

The Role of Endometrial Stem/Progenitor Cells in Recurrent Reproductive Failure

“…In 2020, five markers of receptivity ( ITGβ1 [ 112 ], RAC1 [ 113 ], HOXA11 [ 111 ], ITGβ3 [ 112 , 114 ], and NOGGIN [ 111 ]) were compared between menstrual blood samples taken from women with RIF, versus fertile controls, revealing different patterns of expression. This observation led the authors to propose that aberrant eMSCs contribute to altered endometrial receptivity in women with RIF [ 115 ]. eMSCs from menstrual blood were isolated and characterised based on their morphology and behaviour, expression of specific surface markers (CD44, CD31, CD34, CD73, CD90, and CD105), and capacity to differentiate, all of which was based on the International Society for Cellular Therapy statement [ 115 , 116 ].…”

“…This observation led the authors to propose that aberrant eMSCs contribute to altered endometrial receptivity in women with RIF [ 115 ]. eMSCs from menstrual blood were isolated and characterised based on their morphology and behaviour, expression of specific surface markers (CD44, CD31, CD34, CD73, CD90, and CD105), and capacity to differentiate, all of which was based on the International Society for Cellular Therapy statement [ 115 , 116 ]. Notably, significantly higher expression levels of both HOXA11 and ITG β 3 were seen in the eMSCs of women with RIF [ 115 ].…”

“…eMSCs from menstrual blood were isolated and characterised based on their morphology and behaviour, expression of specific surface markers (CD44, CD31, CD34, CD73, CD90, and CD105), and capacity to differentiate, all of which was based on the International Society for Cellular Therapy statement [ 115 , 116 ]. Notably, significantly higher expression levels of both HOXA11 and ITG β 3 were seen in the eMSCs of women with RIF [ 115 ]. HOXA11 encodes a transcription factor and is involved in proliferation, differentiation, and embryologic development of the endometrium [ 117 ], therefore, HOXA11 is thought to be important in establishing pregnancy [ 111 , 118 ].…”

Psychological Stress and Functional Endometrial Disorders: Update of Mechanism Insights

“…Previous studies have shown that several molecules are expressed and silenced in the uterus during the peri-implantation period, which guides the sequential proliferation and differentiation of different cell types in the uterus (45,(53)(54)(55). Further analysis has shown that defects in uterine receptivity, such as failure of epithelial clearance and aberrant expression of uterine receptivity-related genes, are the main causes for implantation defects (56,57).…”