The effect of Hydrocortisone on implantation through upregulation of tight junction genes: A lab trial study.

Objective: Emotional stress leading to cortisol release is an important infertility factor in females. Increased cortisol levels can significantly affect tight junction proteins and dysregulate the implantation process. This study investigated the effect of exogenous synthetic Cortisol (Hydrocortisone) on the expression of specific genes encoding several junctional proteins in the endometrial epithelial cells.

Methods: Following endometrium sampling from 25 participants, the biopsied tissue was digested and filtered through a cell strainer to prepare endometrial epithelial cells. After confluency, cells were treated with 50, 100, and 200 nM hydrocortisone concentrations and incubated for 24, 48, and 72 hr with repeated treatments every 24hr. qPCR analysis of 4 tight junction genes, including CLDN3, CLDN4, ZO-1, DSG1, and CDH1 was performed. Gene expressions were reported using a relative quantification method.

Results: Higher tight junction gene expression was evident at higher concentrations of Hydrocortisone. A significant increase in expression of CLDN3, CLDN4, ZO-1, DSG1 and CDH1 was observed at 100 nm concentrations of Hydrocortisone compared with the control group during different treatment durations.

Conclusions: In conclusion, Hydrocortisone treatment (at 100 nm concentration) significantly increased the expression of tight junction genes, suggesting that the blastocyst cannot infiltrate the endometrium readily, thus preventing implantation. Glucocorticoids can disrupt implantation by influencing tight junction molecule expression. Thus, the physicians must further investigate the effect of glucocorticoids treatments on implantation.