title: Null mutation of Kruppel-like factor9/basic transcription element binding protein-1 alters peri-implantation uterine development in mice.
abstract: Female mice null for the basic transcription element binding protein-1 (Bteb1) gene have reduced numbers of implanting embryos. We hypothesized that the implantation defect, resulting in subfertility, is a consequence of developmental asynchrony between the embryo and uterine endometrium at peri-implantation. To address this, endometrium from wild-type (WT) and Bteb1(-/-) females at 0.5 to 5.5 days postcoitum (dpc) were evaluated for proliferation (BrdU labeling), apoptosis (TUNEL), and steroid hormone receptor expression (immunohistochemistry). Loss of BTEB1 did not affect serum estrogen (E) and progesterone (P) levels. In stroma (ST), the numbers of progesterone receptor (PGR) and HomeoboxA10 (HOXA10)-expressing cells were lower (3.5 and 4.5 dpc), while those of estrogen receptor-alpha (ESR1) were higher (3.5 dpc), with Bteb1 ablation. The peak of proliferation in luminal epithelium (LE), glandular epithelium (GE), and ST was delayed, while the apoptotic index in all cell types was increased (2.5 dpc) in Bteb1(-/-) relative to WT mice. The numbers of PGR-positive ST cells was negatively correlated with LE proliferation in WT mice; this correlation was lost in Bteb1(-/-) mice and was not observed before 2.5 dpc for both genotypes. Proliferation and apoptosis in all endometrial compartments, as well as the numbers of PGR-, HOXA10-, and ESR1-expressing ST cells, were lower in Bteb1(-/-) relative to WT mice after ovariectomy and E + P treatment. Results suggest that BTEB1, by regulating ST PGR expression and transactivation, participates in the paracrine control of LE proliferation by PGR and thus is important for establishment of a receptive uterus critical for successful implantation.
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock. AR 72202, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Velarde
authors.forename: Yan
authors.initials: Y
authors.lastname: Geng
authors.forename: Renea R
authors.initials: RR
authors.lastname: Eason
authors.forename: Frank A
authors.initials: FA
authors.lastname: Simmen
authors.forename: Rosalia C M
authors.initials: RC
authors.lastname: Simmen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D004967:Estrogens / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000096:biosynthesis; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D018345:Mice, Knockout; D010052:Ovariectomy; D011247:Pregnancy; D011374:Progesterone / Q000502:physiology; D011980:Receptors, Progesterone / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D047628:Estrogen Receptor alpha; D004967:Estrogens; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C489675:Klf9 protein, mouse; D051741:Kruppel-Like Transcription Factors; D011980:Receptors, Progesterone; D014157:Transcription Factors; C092119:Hoxa10 protein, mouse; D011374:Progesterone