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Science 324 (5929): 938-941

Copyright © 2009 by the American Association for the Advancement of Science

MAPK3/1 (ERK1/2) in Ovarian Granulosa Cells Are Essential for Female Fertility

Heng-Yu Fan,1 Zhilin Liu,1 Masayuki Shimada,2 Esta Sterneck,3 Peter F. Johnson,4 Stephen M. Hedrick,5 JoAnne S. Richards1,*

Abstract: A surge of luteinizing hormone (LH) from the pituitary gland triggers ovulation, oocyte maturation, and luteinization for successful reproduction in mammals. Because the signaling molecules RAS and ERK1/2 (extracellular signal–regulated kinases 1 and 2) are activated by an LH surge in granulosa cells of preovulatory follicles, we disrupted Erk1/2 in mouse granulosa cells and provide in vivo evidence that these kinases are necessary for LH-induced oocyte resumption of meiosis, ovulation, and luteinization. In addition, biochemical analyses and selected disruption of the Cebpb gene in granulosa cells demonstrate that C/EBPβ (CCAAT/Enhancer-binding protein–β) is a critical downstream mediator of ERK1/2 activation. Thus, ERK1/2 and C/EBPβ constitute an in vivo LH-regulated signaling pathway that controls ovulation- and luteinization-related events.

1 Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
2 Department of Applied Animal Science, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, 739-8528, Japan.
3 Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute–Frederick, Frederick, MD 21702–1201, USA.
4 Basic Research Laboratory, Center for Cancer Research, National Cancer Institute–Frederick, Frederick, MD 21702–1201, USA.
5 Molecular Biology Section, Division of Biological, Sciences and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.

* To whom correspondence should be addressed. E-mail: joanner{at}bcm.edu

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