Investigation of the Relation between Follicular Atresia and Granulosa Cells in Terms of Cell Death Mechanisms in Premature Ovarian Failure Model

Abstract

Premature Ovarian Failure; is characterized by the dysfunction or early depletion of ovarian reserves due to follicular loss in the ovary in women under age of 40. POF is the important cause of infertility and its etiology is still not clearly understood. Investigation of cell death mechanisms (CDM) that play a role in the follicular atresia (FA) triggered by excessive loss of granulosa cells (GCs) that provide metabolic support for oocyte and follicle development in the ovary will help to understand POF etiology. It was known that apoptosis and autophagy play a role in FA. Recent studies have shown that paraptosis, associated with endoplasmic reticulum stress (ERS), also exist in FA. POF model was established in C57BL/6 female mice by CTX and it was confirmed by increased follicle stimulating hormone (FSH), luteal hormone (LH) and decreased estradiol (E2) blood levels and follicle count. According to the results of the immunohistochemistry (IHC) cell death markers were significantly more expressed than control (C) and sham (S) groups in the POF model. In addition, more apoptotic cells were observed in the POF group compared to C and S in the TUNEL analysis. In consequence of this study apoptosis and autophagy as well as paraptosis play a role in the FA leading to POF, will help to develop new treatment protocols.

Follicular fluid exosomes: Important modulator in proliferation and steroid synthesis of porcine granulosa cells

“…Follicular atresia and premature ovarian failure are related to GCs apoptosis. 40,41 Although significant progress has been made in ovarian physiology, some specific molecular regu- and CCND1 were detected by RT-qPCR. F, The protein levels were detected by western blot analysis.…”

“…GCs are important cellular components of the ovary. Follicular atresia and premature ovarian failure are related to GCs apoptosis 40,41 . Although significant progress has been made in ovarian physiology, some specific molecular regulatory mechanisms for follicular development are still unclear.…”

“…Furthermore, the genes (HSD3B1, CCND1, and B-CATENIN) in the miR-31 mimics+ICG-001 group were lower than the miR-31mimics group (Figure6E,F-a,b), suggesting that miR-31 regulated proliferation and steroid gene expression by activating the WNT/B-CATENIN signaling pathway (Figure7).4 | DISCUSSIONGCs are important cellular components of the ovary. Follicular atresia and premature ovarian failure are related to GCs apoptosis 40,41. Although significant progress has been made in ovarian physiology, some specific molecular regulatory mechanisms for follicular development are still unclear.…”

Similar Repair Effects of Human Placenta, Bone Marrow Mesenchymal Stem Cells, and Their Exosomes for Damaged SVOG Ovarian Granulosa Cells

“…Many studies have confirmed that the selection and atresia of follicles are determined by the apoptosis of GCs [ 47 , 48 ]. In addition, one of the mainstream views on the mechanism underlying the onset of POF caused by chemotherapeutic drugs is that POF is the result of follicular atresia caused by the excessive senescence, apoptosis, and loss of GCs [ 10 , 11 ]. Therefore, it is very important to improve the ovarian functions and restore the fertility of patients by inhibiting the apoptosis of GCs.…”

“…However, the mechanism underlying the POF caused by chemotherapeutic drugs is still unclear [ 9 ]. There are two mainstream views: (1) POF is the result of follicular atresia caused by excessive senescence, apoptosis, and loss of granulosa cells (GCs) [ 10 , 11 ]; and (2) POF is the result of excessive activation of dormant primordial follicles [ 12 , 13 ]. In order to study the mechanism of chemotherapeutic drugs damaging ovarian function, this study chooses phosphoramide mustard (PM) to conduct in vitro cell experiments.…”