Lhx8 regulates primordial follicle activation and postnatal folliculogenesis

BMC Biology

Research Article

Vassilis Pachnis¹  Rita Lopes¹  Yu Ren²  Kayla Golnoski²  Megan McGuire²  Hitomi Suzuki³  Krishna Jagarlamudi⁴  Aleksandar Rajkovic⁵ 

[1] Division of Molecular Neurobiology, MRC National Institute of Medical Research, NW7 1AA, London, UK;Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, 15213, Pittsburgh, PA, USA;Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, 15213, Pittsburgh, PA, USA;Department of Experimental Animal Model for Human Disease, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 113-8510, Bunkyo-ku, Tokyo, Japan;Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, 15213, Pittsburgh, PA, USA;Department of Pathology, University of Pittsburgh, 15213, Pittsburgh, PA, USA;Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, 15213, Pittsburgh, PA, USA;Department of Pathology, University of Pittsburgh, 15213, Pittsburgh, PA, USA;Department of Human Genetics, University of Pittsburgh, 15213, Pittsburgh, PA, USA;

关键词: Lhx8;    Primordial follicle;    Oocyte;    Lin28a;    Ovarian reserve;   

DOI  :  10.1186/s12915-015-0151-3

 received in 2015-02-19, accepted in 2015-06-10,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe early stages of ovarian follicle formation—beginning with the breakdown of germ cell cysts and continuing with the formation of primordial follicles and transition to primary and secondary follicles—are critical in determining reproductive life span and fertility. Previously, we discovered that global knockouts of germ cell-specific transcriptional co-regulators Sohlh1, Sohlh2, Lhx8, and Nobox, cause rapid oocyte loss and ovarian failure. Also factors such as Nobox and Sohlh1 are associated with human premature ovarian failure. In this study, we developed a conditional knockout of Lhx8 to study oocyte-specific pathways in postnatal folliculogenesis.ResultsThe conditional deficiency of Lhx8 in the oocytes of primordial follicles leads to massive primordial oocyte activation, in part, by indirectly interacting with the PI3K-AKT pathway, as shown by synergistic effects on FOXO3 nucleocytoplasmic translocation and rpS6 activation. However, LHX8 does not directly regulate members of the PI3K-AKT pathway; instead, we show that LHX8 represses Lin28a expression, a known regulator of mammalian metabolism and of the AKT/mTOR pathway. LHX8 can bind to the Lin28a promoter, and the depletion of Lin28a in Lhx8-deficient oocytes partially suppresses primordial oocyte activation. Moreover, unlike the PI3K-AKT pathway, LHX8 is critical beyond primordial follicle activation, and blocks the primary to secondary follicle transition.ConclusionsOur results indicate that the LHX8-LIN28A pathway is essential in the earliest stages of primordial follicle activation, and LHX8 is an important oocyte-specific transcription factor in the ovary for regulating postnatal folliculogenesis.

【 授权许可】

Unknown   
© Ren et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.