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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #225237

Title: Delayed Parturition and Altered Myometrial Progesterone Receptor Isoform A Expression in Mice Null for Kruppel-like Factor 9

Author
item ZENG, ZHAOYANG - ACNC/UAMS
item VELARDE, MICHAEL - ACNC/UAMS
item SIMMEN, FRANK - ACNC/UAMS
item SIMMEN, ROSALIA - ACNC/UAMS

Submitted to: Biology of Reproduction
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/15/2008
Publication Date: 5/15/2008
Citation: Zeng, Z., Velarde, M.C., Simmen, F.A., Simmen, R.C. 2008. Delayed parturition and altered myometrial progesterone receptor isoform A expression in mice null for Kruppel-like Factor 9. Biology of Reproduction. 78(6):1029-1037.

Interpretive Summary: Parturition is a complex process that is regulated by many factors. A delay in parturition and prolonged labor can cause significant problems for the mother as well as developmental problems for the infant. In the present study, we found that in mice where the gene for a protein involved in progesterone action is knocked-out, pregnant dams exhibit delayed parturition. The pups born from these dams showed lower birth weights and increased incidence of death. This study provides new data on factors made by the uterus that are important for parturition and which might be helpful in the prevention and treatment of this condition in humans.

Technical Abstract: Pre-term and delayed labor conditions are devastating health problems, with currently unknown etiologies. We previously showed that the transcription factor Krüppel-like factor 9 (KLF9) influences the expression and/or transcriptional activity of receptors for estrogen and progesterone in endometrial cells in vivo and in vitro. Given that estrogen and progesterone differentially regulate uterine myometrial contractility during gestation, we hypothesized that lack of KLF9 could compromise myometrial function, leading to defects in parturition. To test this, we used mice null for KLF9 to evaluate gestation length; response to the progesterone receptor (PGR) antagonist RU486; and expression levels of steroid receptor proteins, nuclear receptor coactivator and contractility-associated genes, and NF-kappaB DNA binding activity in myometrium near term. KLF9 knockout (KO) mice exhibited delayed parturition by one to two days relative to wildtype (WT) counterparts, in the absence of fetal genotype contribution and differences in serum estrogen and progesterone levels. KO mice near term were refractory to the abortive action of RU486, and displayed aberrant myometrial expression patterns of nuclear PGR-A and NF-kappaB p65/RELA, relative to WT mice. Myometrial expression levels of nuclear estrogen receptor-alpha did not differ, while those for Oxtr and Crebbp mRNAs were lower, in KO vs. WT mice. Results indicate that KLF9 contributes to the regulation of PGR-associated components in the myometrium necessary for timely onset of parturition in mice. The present study highlights the potential utility of KLF9 null mice to investigate pathophysiology of parturition defects involving PGR signaling.