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Article

Role of Klf4 in the Regulation of Apoptosis and Cell Cycle in Rat Granulosa Cells during the Periovulatory Period

Laboratory of Reproductive Endocrinology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul 133-791, Korea
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(1), 87; https://doi.org/10.3390/ijms20010087
Received: 3 December 2018 / Revised: 21 December 2018 / Accepted: 23 December 2018 / Published: 26 December 2018
In the ovary, the luteinizing hormone (LH) surge suppresses the proliferation and induces the luteinization of preovulatory granulosa cells (GCs), which is crucial for the survival of terminally-differentiated GCs. Krüppel-like factor 4 (Klf4) has been shown to play a role in regulating the cell cycle and apoptosis in various cell types. The rapid induction of Klf4 expressions by LH was observed in preovulatory GCs. To evaluate whether Klf4 affects GC proliferation and survival, primary rat GCs were isolated from pregnant mare serum gonadotropin-primed Sprague–Dawley rat ovaries and transfected with a Klf4 expression vector or Klf4-specific siRNA, followed by determination of the transcript levels of apoptosis-related and cell cycle-related genes. Cell proliferation, viability, and apoptosis were analyzed by BrdU incorporation, a Cell Counting Kit-8 assay, a bioluminescence caspase 3/7 assay, and flow cytometry. LH treatment increased Klf4 mRNA expression in preovulatory GCs. Transcripts of B-cell lymphoma 2 (Bcl-2) and cell cycle promoters (Cyclin D1 and Cyclin D2) decreased, whereas those of the cell cycle inhibitor, p21, increased. Altering the expression of Klf4 by overexpression or knockdown consistently affected the expression of Bcl-2 and Cyclin D1. In agreement with this, Klf4 overexpression reduced cell viability, increased the fraction of apoptotic cells, and arrested cell cycle progression in G1 phase. We conclude that Klf4 increases the susceptibility of preovulatory GCs to apoptosis by down-regulating Bcl-2, and promotes LH-induced cell cycle exit. It appears to be a key regulator induced by the LH surge that determines the fate of GCs in preovulatory follicles during the luteal transition. View Full-Text
Keywords: Klf4; granulosa cells; LH surge; apoptosis; cell cycle Klf4; granulosa cells; LH surge; apoptosis; cell cycle
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MDPI and ACS Style

Choi, H.; Roh, J. Role of Klf4 in the Regulation of Apoptosis and Cell Cycle in Rat Granulosa Cells during the Periovulatory Period. Int. J. Mol. Sci. 2019, 20, 87. https://doi.org/10.3390/ijms20010087

AMA Style

Choi H, Roh J. Role of Klf4 in the Regulation of Apoptosis and Cell Cycle in Rat Granulosa Cells during the Periovulatory Period. International Journal of Molecular Sciences. 2019; 20(1):87. https://doi.org/10.3390/ijms20010087

Chicago/Turabian Style

Choi, Hyeonhae; Roh, Jaesook. 2019. "Role of Klf4 in the Regulation of Apoptosis and Cell Cycle in Rat Granulosa Cells during the Periovulatory Period" Int. J. Mol. Sci. 20, no. 1: 87. https://doi.org/10.3390/ijms20010087

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