Submitted March 21, 2008
Returned for revision April 4, 2008
Accepted May 2, 2008
Gamete Biology
Lim Homeobox Gene, LHX8, Is Essential for Mouse Oocyte Differentiation and Survival
Youngsok Choi ,
Daniel J. Ballow ,
Yun Xin ,
and
Aleksandar Rajkovic *
* To whom correspondence should be addressed. E-mail: rajkovic{at}bcm.tmc.edu.
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 drastic the down-regulation of Kit and Kitl in Lhx8-/- ovaries. We compared Lhx8-/- and wild-type ovaries using Affymetrix 430 2.0 microarray platform. Eighty (44%) of 180 of the genes down-regulated more than 5-fold in Lhx8-/- ovaries were preferentially expressed in oocytes, whereas only 3 (2%) of 146 genes up-regulated 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 is 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 down-regulating the Nobox pathway.
Key words:
Gamete Biology •
Ovary •
Developmental biology •
Gene regulation •
Oocyte development
