Article

Kruppel-like factor 5 (KLF5) is critical for conferring uterine receptivity to implantation

Division of Reproductive Sciences, Perinatal Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 01/2012; 109(4):1145-50. DOI: 10.1073/pnas.1118411109
Source: PubMed

ABSTRACT

A blastocyst will implant only when the uterus becomes receptive. Following attachment, luminal epithelial cells undergo degeneration at the site of the blastocyst. Although many genes critical for uterine receptivity are primarily regulated by ovarian hormones, Kruppel-like factor 5 (KLF5), a zinc finger-containing transcription factor, is persistently expressed in epithelial cells independently of ovarian hormones. Loss of uterine Klf5 causes female infertility due to defective implantation. Cox2 is normally expressed in the luminal epithelium and stroma at the site of blastocyst attachment, but luminal epithelial COX2 expression is absent with loss of Klf5. This is associated with the retention of the epithelium around the implantation chamber with arrested embryonic growth. These results suggest that Klf5 is indispensable for normal implantation.

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Available from: Huirong Xie, Feb 19, 2014
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    • "Several KLFs have been directly linked to the regulation of inflammatory signaling, defects of which may contribute to uterine pathology. In particular, uterine-specific Klf5-null mice are infertile due to aberrant expression of the prostaglandin synthesis gene Ptgs2, resulting in the enhanced expression of COX2 (Sun et al. 2012). Similarly, KLF11, the attenuated expression of which is linked to uterine leiomyoma, has been reported to inhibit prostaglandin E 2 synthesis by transcriptionally silencing the promoter of the gene encoding phospholipase A 2a , the key enzyme for prostaglandin biosynthesis (Buttar et al. 2010). "
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    ABSTRACT: Female reproductive tract pathologies arise largely from dysregulation of estrogen and progesterone receptor signaling leading to aberrant cell proliferation, survival and differentiation. The signaling pathways orchestrated by these nuclear receptors are complex, require the participation of many nuclear proteins serving as key binding partners or targets and involve a range of paracrine and autocrine regulatory circuits. Members of the Krüppel-like family of transcription factors are ubiquitously expressed in reproductive tissues and have been increasingly implicated as critical co-regulators and integrators of steroid hormone actions. Here we explore the involvement of KLF family members in uterine pathology, describe their currently known molecular mechanisms and discuss their potential as targets for therapeutic intervention.
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    • "This fi nding was later confi rmed (Nallasamy et al. 2012 ). Kruppel-like factor 5 (Klf5), a zinc fi nger–containing transcription factor, is also not directly regulated by ovarian hormones in the uterus but is nevertheless critical for implantation, as mice with uterine deletion of Klf5 are infertile that results from defective implantation (Sun et al. 2012 ). In mouse uteri, Klf5 is expressed in the luminal and glandular epithelia until day 5 of pregnancy when decidualization begins. "
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    ABSTRACT: Embryo implantation is a complex process involving endocrine, para-crine, autocrine, and juxtacrine modulators that span cell–cell and cell–matrix interactions. The quality of implantation is predictive for pregnancy success. Earlier observational studies formed the basis for genetic and molecular approaches that ensued with emerging technological advances. However, the precise sequence and details of the molecular interactions involved have yet to be defi ned. This review refl ects briefl y on aspects of our current understanding of rodent implantation as a tribute to Roger Short's lifelong contributions to the fi eld of reproductive physiology.
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    • "This fi nding was later confi rmed (Nallasamy et al. 2012 ). Kruppel-like factor 5 (Klf5), a zinc fi nger–containing transcription factor, is also not directly regulated by ovarian hormones in the uterus but is nevertheless critical for implantation, as mice with uterine deletion of Klf5 are infertile that results from defective implantation (Sun et al. 2012 ). In mouse uteri, Klf5 is expressed in the luminal and glandular epithelia until day 5 of pregnancy when decidualization begins. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Embryo implantation is a complex process involving endocrine, para-crine, autocrine, and juxtacrine modulators that span cell–cell and cell–matrix interactions. The quality of implantation is predictive for pregnancy success. Earlier observational studies formed the basis for genetic and molecular approaches that ensued with emerging technological advances. However, the precise sequence and details of the molecular interactions involved have yet to be defi ned. This review refl ects briefl y on aspects of our current understanding of rodent implantation as a tribute to Roger Short's lifelong contributions to the fi eld of reproductive physiology.
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