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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #201085
Title: Gene deletion of KLF9 in mice results in aberrant endometrial proliferation and myometrial function

Author
item VELARDE, MICHAEL - UAMS GRAD STUDENT
item GENG, YAN - ACNC/UAMS
item SIMMEN, FRANK - ACNC/UAMS
item SIMMEN, ROSALIA - ACNC/UAMS

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 8/4/2006
Publication Date: N/A
Citation: N/A

Interpretive Summary: A properly timed development of the uterus is very important for successful pregnancy. Here, we demonstrated the involvement of a protein called KLF9 in controlling the function of the uterus during early and late stages of pregnancy, hence contributing to a better understanding of the mechanism involved in normal development of the uterus. Future work will involve how diet an nutritional status affect reproductive process related to uterian function.

Technical Abstract: Timely regulation of uterine function is critical for successful pregnancy. Our laboratory has previously identified Basic transcription element binding protein-1/Krüppel-like factor 9 (Bteb1/Klf9), a member of Sp/KLF family of transcription factor, as a progesterone receptor (Pgr) interacting protein. Klf9 is expressed predominantly in uterine endometrial stroma and myometrium. Female mice null for Klf9 (KO) are sub-fertile with reduced litter size and numbers of successfully implanting embryos. Moreover, while only 71% of KO mice exhibiting copulatory plugs at day post coitum (dpc) 0.5 maintained gestation to term, wild type (WT) had 100% pregnancy success. At peri-implantation, uterine luminal epithelium of KO exhibited a delayed peak in proliferation (dpc3.5) compared to WT (dpc2.5). The uterine transcript levels for insulin-like growth factor-1, keratinocyte growth factor, estrogen receptor and Pgr were differentially expressed in KO relative to WT at early pregnancy. Endometrial proliferative response (PCNA immunoreactivity) to estrogen but not progesterone was lost in ovariectomized KO mice. Parturition in KO mice occurred at dpc 20.5 compared to WT mice (dpc 19.5), and this was accompanied by higher labor complications in KO (10.5%) relative to WT (1%) dams, irrespective of male partner genotype. Serum estrogen and progesterone levels did not differ between WT and KO. Myometrial Pgr-C and oxytocin receptor mRNA and Pgr-B protein levels were altered in KO relative to WT at parturition. Results demonstrate that the reproductive phenotypes of KO mice are due partly to dysregulated uterine proliferation and gene expression and implicate Klf9 in uterine signaling critical for successful pregnancy.