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There is general agreement that granulosa cell apoptosis is the cause of antral follicle attrition. Less clear is whether this pathway is also activated in case of preantral follicle degeneration, as several reports mention that the incidence of granulosa cell apoptosis in preantral follicles is negligible. Our objective is therefore to determine which cell-death pathways are involved in preantral and antral follicular degeneration.Atretic preantal and antral follicles were investigated using immunohistochemistry and laser-capture micro-dissection followed by qRT-PCR. Microtubule-associated light-chain protein 3 (LC3), sequestosome 1 (SQSTM1/P62), Beclin1, autophagy-related protein 7 (ATG7) and cleaved caspase 3 (cCASP3) were used as markers for autophagy and apoptosis, respectively. P62 immunostaining was far less intense in granulosa cells of atretic compared to healthy preantral follicles, while no difference in LC3 and BECLIN1 immunostaining intensity was observed. This difference in P62 immunostaining was not observed in atretic antral follicles. mRNA levels of LC3 and p62 were not different between healthy and atretic (pre)antral follicles. ATG7 immunostaining was observed in granulosa cells of preantral atretic follicles, not in granulosa cells of degenerating antral follicles. The number of cCASP3 positive cells was negligible in preantral atretic follicles, while numerous in atretic antral follicles. Taken together, we conclude that preantral and antral follicular atresia is the result of activation of different cell-death pathways as antral follicular degeneration is initiated by massive granulosa cell apoptosis, while preantral follicular atresia occurs mainly via enhanced granulosa cell autophagy.
This article was published in the following journal.
Name: Biology of reproduction
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The degeneration and resorption of an OVARIAN FOLLICLE before it reaches maturity and ruptures.
Sarcoma of FOLLICULAR DENDRITIC CELLS most often found in the lymph nodes. This rare neoplasm occurs predominately in adults.
The period of the MENSTRUAL CYCLE representing follicular growth, increase in ovarian estrogen (ESTROGENS) production, and epithelial proliferation of the ENDOMETRIUM. Follicular phase begins with the onset of MENSTRUATION and ends with OVULATION.
Proteins and enzymes that function, often as components of MULTIPROTEIN COMPLEXES, to assemble AUTOPHAGOSOMES and carry out AUTOPHAGY.
An autophagy related protein that is similar to UBIQUITIN-ACTIVATING ENZYME E1. It functions in CYTOPLASM to VACUOLE transport (Cvt) and AUTOPHAGY by activating ATG12 PROTEIN for its conjugation with ATG5 PROTEIN, as well as the conjugation of ATG8 FAMILY PROTEINS with phosphatidylethanolamine for ATG8 association to Cvt vesicles and AUTOPHAGOSOME membranes. It is also required for the nitrogen starvation response in yeast, MITOPHAGY; and autophagic cell death induced by CASPASE 8 inhibition.
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