期刊
BIOLOGY OF REPRODUCTION
卷 79, 期 3, 页码 442-449出版社
SOC STUDY REPRODUCTION
DOI: 10.1095/biolreprod.108.069393
关键词
developmental biology; gamete biology; gene regulation; KIT; KITL; meiosis; LHX8; NOBOX; oocyte development; oogenesis; ovary; primordial follicle
资金
- NICHD NIH HHS [R01 HD044858, HD44858] Funding Source: Medline
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 Kid 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.
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