Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice.

SMAD4 is a central component of the TGFbeta superfamily signaling pathway. Within the ovary, TGFbeta-related proteins play crucial roles in controlling granulosa cell growth, differentiation, and steroidogenesis. To study the in vivo roles of SMAD4 during follicle development, we generated an ovaria...

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Main Authors: Pangas, SA, Li, X, Robertson, E, Matzuk, M
格式: Journal article
语言:English
出版: 2006
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author Pangas, SA
Li, X
Robertson, E
Matzuk, M
author_facet Pangas, SA
Li, X
Robertson, E
Matzuk, M
author_sort Pangas, SA
collection OXFORD
description SMAD4 is a central component of the TGFbeta superfamily signaling pathway. Within the ovary, TGFbeta-related proteins play crucial roles in controlling granulosa cell growth, differentiation, and steroidogenesis. To study the in vivo roles of SMAD4 during follicle development, we generated an ovarian conditional knockout of Smad4 using the cre/loxP recombination system. Smad4 ovarian-specific knockout mice are subfertile with decreasing fertility over time and multiple defects in folliculogenesis. Regulation of steroidogenesis is disrupted in the Smad4 conditional knockout, leading to increased levels of serum progesterone. In addition, severe cumulus cell defects are present both in vivo and when assayed in vitro. These findings demonstrate that disrupting signaling through SMAD4 in the ovarian granulosa cells leads to premature luteinization of granulosa cells and eventually premature ovarian failure, thereby demonstrating key in vivo roles of TGFbeta superfamily signaling in the timing of granulosa cell differentiation.
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spelling oxford-uuid:5a3c8412-606f-454b-b465-3e2f330da5e22022-03-26T17:14:38ZPremature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5a3c8412-606f-454b-b465-3e2f330da5e2EnglishSymplectic Elements at Oxford2006Pangas, SALi, XRobertson, EMatzuk, MSMAD4 is a central component of the TGFbeta superfamily signaling pathway. Within the ovary, TGFbeta-related proteins play crucial roles in controlling granulosa cell growth, differentiation, and steroidogenesis. To study the in vivo roles of SMAD4 during follicle development, we generated an ovarian conditional knockout of Smad4 using the cre/loxP recombination system. Smad4 ovarian-specific knockout mice are subfertile with decreasing fertility over time and multiple defects in folliculogenesis. Regulation of steroidogenesis is disrupted in the Smad4 conditional knockout, leading to increased levels of serum progesterone. In addition, severe cumulus cell defects are present both in vivo and when assayed in vitro. These findings demonstrate that disrupting signaling through SMAD4 in the ovarian granulosa cells leads to premature luteinization of granulosa cells and eventually premature ovarian failure, thereby demonstrating key in vivo roles of TGFbeta superfamily signaling in the timing of granulosa cell differentiation.
spellingShingle Pangas, SA
Li, X
Robertson, E
Matzuk, M
Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice.
title Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice.
title_full Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice.
title_fullStr Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice.
title_full_unstemmed Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice.
title_short Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice.
title_sort premature luteinization and cumulus cell defects in ovarian specific smad4 knockout mice
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AT robertsone prematureluteinizationandcumuluscelldefectsinovarianspecificsmad4knockoutmice
AT matzukm prematureluteinizationandcumuluscelldefectsinovarianspecificsmad4knockoutmice