EVALUATION OF ENDOPLASMIC RETICULUM STRESS IN GRANULOSA CELLS OF INFERTILE PATIENTS DIAGNOSED WITH ENDOMETRIOMA AND INVESTIGATION OF ITS EFFECT ON OOCYTE QUALITY

Abstract

Objective

Endometriosis is a disease characterized by the implantation and growth of endometrial tissue outside the uterus in women of reproductive age, and its etiopathogenesis remains unclear. It is most commonly seen in the ovaries (endometrioma). It is estimated that it negatively affects folliculogenesis, ovulation, embryogenesis and causes infertility by causing endoplasmic reticulum (ER) stress in the ovary through different mechanisms. ER stress occurs when cell homeostasis is disrupted as a result of the accumulation of unfolded or misfolded proteins. In this case, the cell first activates ER stress response pathways, aiming to restore homeostasis and keep the cell alive. If ER stress cannot be coped with, the cell is directed to apoptosis. The aim in our study is to determine the local and/or systemic negative effects of endometriosis on the ovary, the endoplasmic reticulum stress it creates in the ovaries as a result of these effects, and which pathway or pathways are activated in case of stress.

Materials and methods

ER stress parameters (GADD34, Caspase12, Caspase3, BIP, CHOP, XBP1, ATF4) were investigated using ELISA method in granulosa cells, which are waste cells collected during oocyte retrieval after in vitro fertilization (IVF) treatment from infertile patients diagnosed with unilateral endometrioma and healthy female patients diagnosed with male factor and will not be used in IVF treatment. The study design was planned in 3 groups; Group 1: ovary with endometrioma diagnosed with unilateral endometrioma (n=23), Group 2: ovary without endometrioma diagnosed with unilateral endometrioma (n=23), Group 3: control group male factor (n=20).

Conclusions

Although no significant difference was observed in ovarian and embryological parameters between the two groups with and without endometrioma, a significantly lower total antral follicle count, AMH levels, oocyte retrieval numbers, oocyte maturation, and embryo quality were detected when compared to the control group. As the size of the endometrioma increased, particularly when exceeding a threshold of 4 cm, it was found that the PERK pathway, an ER stress pathway, as well as the caspase apoptotic process, were activated. We can say that the PERK pathway is primarily preferred among the ER stress pathways examined in the endometrioma group and by dimensioning. The results can be supported by more comprehensive studies.