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.
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas 77030, USA.
Youngsok
Y
Choi
Daniel J
DJ
Ballow
Yun
Y
Xin
Aleksandar
A
Rajkovic
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