Maternal heparin-binding-EGF deficiency limits pregnancy success in mice.

Maternal heparin-binding-EGF deficiency limits pregnancy success in mice. Research Abstract Details 

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Maternal heparin-binding-EGF deficiency limits pregnancy success in mice. Abstract Text:

Huirong Xie,Haibin Wang,Susanne Tranguch,Ryo Iwamoto,Eisuke Mekada,Francesco J Demayo,John P Lydon,Sanjoy K Das,Sudhansu K Dey,Huirong Xie,Haibin Wang,Susanne Tranguch,Ryo Iwamoto,Eisuke Mekada,Francesco J Demayo,John P Lydon,Sanjoy K Das,Sudhansu K Dey,

An intimate discourse between the blastocyst and uterus is essential for successful implantation. However, the molecular basis of this interaction is not clearly understood. Exploiting genomic Hbegf mutant mice, we show here that maternal deficiency of heparin-binding EGF-like growth factor (HB-EGF) defers on-time implantation, leading to compromised pregnancy outcome. We also demonstrate that amphiregulin, but not epiregulin, partially compensates for the loss of HB-EGF during implantation. In search of the mechanism of this compensation, we found that reduced preimplantation estrogen secretion from ovarian HB-EGF deficiency is a cause of sustained expression of uterine amphiregulin before the initiation of implantation. To explore the significance specifically of uterine HB-EGF in implantation, we examined this event in mice with conditional deletion of uterine HB-EGF and found that this specific loss of HB-EGF in the uterus still defers on-time implantation without altering preimplantation ovarian estrogen secretion. The observation of normal induction of uterine amphiregulin surrounding the blastocyst at the time of attachment in these conditional mutant mice suggests a compensatory role of amphiregulin for uterine loss of HB-EGF, preventing complete failure of pregnancy. Our study provides genetic evidence that HB-EGF is critical for normal implantation. This finding has high clinical relevance, because HB-EGF signaling is known to be important for human implantation.

Maternal heparin-binding-EGF deficiency limits pregnancy success in mice. Publishing Authors By Initials

H Xie,H Wang,S Tranguch,R Iwamoto,E Mekada,FJ Demayo,JP Lydon,SK Das,SK Dey,H Xie,H Wang,S Tranguch,R Iwamoto,E Mekada,FJ Demayo,JP Lydon,SK Das,SK Dey,

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Maternal heparin-binding-EGF deficiency limits pregnancy success in mice. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 18315-20

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 1091-6490

DAY: 6

MONTH: 11

YEAR: 2007

Maternal heparin-binding-EGF deficiency limits pregnancy success in mice. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

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Grant and Affiliation Information for Maternal heparin-binding-EGF deficiency limits pregnancy success in mice.

AFFILIATION: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Country: United States

AGENCY: United States NICHD

GRANT: U54-HD28934

ACRONYM: HD

MEDLINETA: Proc Natl Acad Sci U S A

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