AMPK is required for uterine receptivity and normal responses to steroid hormones

被引:18
|
作者
Griffiths, Richard M. [1 ,2 ]
Pru, Cindy A. [1 ,2 ]
Behura, Susanta K. [3 ,4 ]
Cronrath, Andrea R. [1 ,2 ]
McCallum, Melissa L. [1 ,2 ]
Kelp, Nicole C. [1 ,2 ]
Winuthayanon, Wipawee [1 ,2 ]
Spencer, Thomas E. [3 ,4 ]
Pru, James K. [1 ,2 ]
机构
[1] Washington State Univ, Sch Mol Biosci, Dept Anim Sci, Pullman, WA 99164 USA
[2] Washington State Univ, Ctr Reprod Biol, Pullman, WA 99164 USA
[3] Univ Missouri, Div Anim Sci, Columbia, MO USA
[4] Univ Missouri, Dept Obstet Gynecol & Womens Hlth, Columbia, MO USA
基金
美国国家卫生研究院;
关键词
ACTIVATED PROTEIN-KINASE; BLASTOCYST IMPLANTATION; PROGESTERONE SECRETION; EMBRYO IMPLANTATION; STROMAL CELLS; GROWTH-FACTOR; LIF RECEPTOR; MOUSE UTERUS; EXPRESSION; METFORMIN;
D O I
10.1530/REP-19-0402
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
We previously demonstrated that 5'-AMP-activated protein kinase (AMPK) is essential for normal reproductive functions in female mice. Conditional ablation of Prkaa1 and Prkaa2, genes that encode the alpha 1 and alpha 2 catalytic domains of AMPK, resulted in early reproductive senescence, faulty artificial decidualization, uterine inflammation and fibrotic postparturient endometrial regeneration. We also noted a delay in the timing of embryo implantation in Prkaa1/2(d/d) female mice, suggesting a role for AMPK in establishing uterine receptivity. As outlined in new studies here, conditional uterine ablation of Prkaa1/2 led to an increase in ESR1 in the uteri of Prkaa1/2(d/d) mice, resulting in prolonged epithelial cell proliferation and retention of E-2-induced gene expression (e.g. Msx1, Muc1, Ltf) through the implantation window. Within the stromal compartment, stromal cell proliferation was reduced by five-fold in Prkaa1/2(d/d) mice, and this was accompanied by a significant decrease in cell cycle regulatory genes and aberrant expression of decidualization marker genes such as Hand2, Bmp2, Fst and Inhbb. This phenotype is consistent with our prior study, demonstrating a failure of the Prkaa1/2(d/d) uterus to undergo decidualization. Despite these uterine defects, ovarian function seemed to be normal following ablation of Prkaa1/2(d/d) from peri-ovulatory follicles in which ovulation, luteinization and serum progesterone levels were not different on day 5 of pregnancy or pseudopregnancy between Prkaa1/2(fl/fl) and Prkaa1/2(d/d) mice. These cumulative findings demonstrate that AMPK activity plays a prominent role in mediating several steroid hormone-dependent events such as epithelial cell proliferation, uterine receptivity and decidualization as pregnancy is established.
引用
收藏
页码:707 / 717
页数:11
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