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BOR - Papers in Press, published online ahead of print May 28, 2008.
Biol Reprod 2008, 10.1095/biolreprod.108.069393
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BIOLOGY OF REPRODUCTION 79, 442–449 (2008)
DOI: 10.1095/biolreprod.108.069393
© 2008 by the Society for the Study of Reproduction, Inc.

research-article

Lim Homeobox Gene, Lhx8, Is Essential for Mouse Oocyte Differentiation and Survival1

Youngsok Choi 3 4, Daniel J. Ballow 3, Yun Xin 3, and Aleksandar Rajkovic 2 3

Department of Obstetrics and Gynecology,3 Baylor College of Medicine, Houston, Texas 77030 Fertility Center of CHA General Hospital,4 CHA Research Institute, Pochon CHA University, Seoul 135–081, Republic of Korea

ABSTRACT

Lhx8 is a member of the LIM-homeobox transcription factor family and preferentially expressed in oocytes and germ cells within the mouse ovary. We discovered that Lhx8 knockout females lose oocytes within 7 days after birth. At the time of birth, histological examination shows that Lhx8-deficient (Lhx8–/–) ovaries are grossly similar to the newborn wild-type ovaries. Lhx8–/– ovaries fail to maintain the primordial follicles, and the transition from primordial to growing follicles does not occur. Lhx8–/– ovaries misexpress oocyte-specific genes, such as Gdf9, Pou5f1, and Nobox. Very rapid loss of oocytes may partly be due to the drastic downregulation of Kit and Kitl in Lhx8–/– ovaries. We compared Lhx8–/– and wild-type ovaries using an Affymetrix 430 2.0 microarray platform. A total of 80 (44%) of 180 of the genes downregulated more than 5-fold in Lhx8–/– ovaries were preferentially expressed in oocytes, whereas only 3 (2%) of 146 genes upregulated more than 5-fold in the absence of Lhx8 were preferentially expressed in oocytes. In addition, the comparison of genes regulated in Lhx8–/– and Nobox–/– newborn ovaries discovered a common set of 34 genes whose expression level was affected in both Lhx8- and Nobox-deficient mice. Our findings show that Lhx8 is a critical factor for maintenance and differentiation of the oocyte during early oogenesis, and it acts in part by downregulating the Nobox pathway.

developmental biology, gamete biology, gene regulation, KIT, KITL, meiosis, LHX8, NOBOX, oocyte development, oogenesis, ovary, primordial follicle

FOOTNOTES

1 Supported by National Institutes of Health grant HD44858 (A.R.) and March of Dimes Basil O'Connor Award 5-FY02-266 (A.R.).

Correspondence: 2Aleksandar Rajkovic, Department of Obstetrics and Gynecology, Baylor College of Medicine, 1709 Dryden Rd., Suite 1100, Houston, TX 77030. FAX: 713 798 2744; e-mail: rajkovic{at}bcm.edu






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Copyright © 2008 by the Society for the Study of Reproduction.