Thesis
A role for adenosine monophosphate-activated protein kinase (AMPK) in steroid hormone signaling and uterine receptivity
Washington State University
Master of Science (MS), Washington State University
05/2019
DOI:
https://doi.org/10.7273/000004003
Handle:
https://hdl.handle.net/2376/124944
Abstract
Approximately 6% of reproductive age women in the United States are infertile. Many such women seek Assisted Reproductive Technologies (ART) to overcome limitations to their reproductive capacity. A large and increasing percentage of women who require ART to become pregnant in first world countries are obese. Interestingly, the nutrient sensing signaling molecule adenosine monophosphate-activated protein kinase (AMPK) is down-regulated both in expression and enzymatic activity in obese women. Our lab recently established that when AMPK is not active in the female reproductive tract the result is subfertility that rapidly progresses to infertility. Additional consequences include accumulation of fibrotic tissue in the endometrial compartment that increases with each parity and endometrial inflammation, both indicative of endometritis. One possible cause of the infertility phenotype in these mutant mice is faulty steroid hormone signaling during the establishment of pregnancy. The purpose of the studies described herein are to test the hypothesis that AMPK functions to mediate some of the actions of steroid hormones within the female reproductive tract and to establish a receptive endometrium at the time of embryo implantation. The general approach was to compare steroid hormone responses and evaluate uterine receptivity in sexually mature control mice, that have AMPK in their reproductive tract, and the mutant mice. Immunohistochemistry and RT-qPCR were used to demonstrate that gene clusters associated with estrogen (E2) signaling, decidualization, cell cycle progression and inflammation were all differentially regulated in mutant uteri at the time of embryo implantation. These findings were also confirmed in an artificial model of uterine receptivity. To further verify that the ablation of AMPK from the female reproductive tract was in fact a uterine phenotype, we evaluated ovarian histology and serum progesterone (P4) of day of pregnancy 5 animals. The results showed no difference in serum P4 or ovarian histology between control and mutant mice suggesting that production of P4 occurs in an AMPK-independent fashion. Furthermore, uteri from mutant mice failed to respond properly to E2-induced epithelial proliferation, demonstrating that AMPK is a necessary mediator of E2 actions. These results define a new role for AMPK in the context of female reproduction.
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Details
- Title
- A role for adenosine monophosphate-activated protein kinase (AMPK) in steroid hormone signaling and uterine receptivity
- Creators
- RICHARD MELTON GRIFFITHS - Washington State University, UNKNOWN
- Contributors
- JAMES K PRU (Advisor)
- Awarding Institution
- Washington State University
- Academic Unit
- Department of Animal Sciences
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University
- Identifiers
- 99900890796901842
- Language
- English
- Resource Type
- Thesis