Lim homeobox gene, lhx8, is essential for mouse oocyte differentiation and survival.
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.
Choi
Youngsok
Y
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA.
Ballow
Daniel J
DJ
Xin
Yun
Y
Rajkovic
Aleksandar
A
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D060850:LIM-Homeodomain Proteins; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009865:Oocytes / Q000378:metabolism / Q000502:physiology*; D009866:Oogenesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D018398:Homeodomain Proteins; C112960:LIM homeobox protein 8; D060850:LIM-Homeodomain Proteins; C456265:Og2x protein, mouse; D014157:Transcription Factors