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14 May 2018 Preantral follicular atresia occurs mainly through autophagy, while antral follicles degenerate mostly through apoptosis
Li Meng, Sabrina Z. Jan, Geert Hamer, Ans M. van Pelt, Inge van der Stelt, Jaap Keijer, Katja J. Teerds
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Abstract

There is a 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 lasercapture microdissection followed by quantitative real-time reverse transcription polymerase chain reaction. 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.

Summary Sentence

Preantral and antral follicles make use of different cell-death pathways, as antral follicular degeneration is initiated by massive granulosa cell apoptosis, while preantral follicular atresia is mainly dependent on enhanced granulosa cell autophagy.

© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Li Meng, Sabrina Z. Jan, Geert Hamer, Ans M. van Pelt, Inge van der Stelt, Jaap Keijer, and Katja J. Teerds "Preantral follicular atresia occurs mainly through autophagy, while antral follicles degenerate mostly through apoptosis," Biology of Reproduction 99(4), 853-863, (14 May 2018). https://doi.org/10.1093/biolre/ioy116
Received: 17 March 2017; Accepted: 11 May 2018; Published: 14 May 2018
JOURNAL ARTICLE
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KEYWORDS
Apoptosis
atresia
autophagy
granulosa cells
mitochondria
ovary
preantral and antral follicles
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