Lhx8 regulates primordial follicle activation and postnatal folliculogenesisReportar como inadecuado

Lhx8 regulates primordial follicle activation and postnatal folliculogenesis - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Biology

, 13:39

First Online: 16 June 2015Received: 19 February 2015Accepted: 10 June 2015DOI: 10.1186-s12915-015-0151-3

Cite this article as: Ren, Y., Suzuki, H., Jagarlamudi, K. et al. BMC Biol 2015 13: 39. doi:10.1186-s12915-015-0151-3


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.

KeywordsLhx8 Primordial follicle Oocyte Lin28a Ovarian reserve Abbreviationsbpbase pair

ChIPChromatin immunoprecipitation

IgGImmunoglobulin G

PASPeriodic acid–Schiff

PCRPolymerase chain reaction

PDpostnatal day

PFAPrimordial follicle activation

qPCRQuantitative polymerase chain reaction

RNA-seqRNA sequencing

RT-qPCRreal-time quantitative polymerase chain reaction

Yu Ren, Hitomi Suzuki and Krishna Jagarlamudi contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s12915-015-0151-3 contains supplementary material, which is available to authorized users.

Download fulltext PDF


Fuente: https://link.springer.com/

Documentos relacionados