Thesis
PRKAA1 and PRKAA2 are functionally required for endometrial regeneration following parturition and fertility in the female
Washington State University
Master of Science (MS), Washington State University
2015
Handle:
https://hdl.handle.net/2376/103512
Abstract
AMP-activated protein kinase (AMPK) is a well conserved protein complex that acts as a mammalian fuel gauge. When cellular ATP is depleted, AMPK activates energy producing catabolic processes such as glucose transport and fatty acid oxidation while inhibiting anabolic processes like translation and fatty acid synthesis to reestablish cellular energy homeostasis. Pregnancy is a period of high energy use and mechanisms of energy regulation during gestation are not well known. AMPK is expressed in most reproductive organs including the ovary, uterus, mammary, and pituitary. As expression has been conserved and is found robustly in the female reproductive tract, we hypothesize that conditional ablation of Prkaa1 and Prkaa2 genes, which encode the [alpha]1 and [alpha]2 catalytic subunits of AMPK, will result in disrupted female reproductive function in the mouse. Conditional ablation of Prkaa1 Prkaa2 using the progesterone receptor-cre recombinase transgenic mouse resulted in subfertility and premature reproductive senescence. While the first pregnancy yielded comparable numbers of pups between control and Prkaa1 and Prkaa2 double conditional knockout (dcKO) female mice during a six month breeding trial, each subsequent pregnancy yielded progressively fewer pups in the dcKO mice. A lactational phenotype was also observed in dcKO mothers. This subfertility phenotype is likely due to improper uterine involution. Uterine histoarchitecture of dcKO female mice showed disorganization in both the endometrial and myometrial compartments following parturition. Stromal scarring and formation of benign stromal cell tumors were also present in aged dcKO mice. The dcKO mice had normal ovarian histology and estrous cyclicity so it is unlikely that faulty ovary or pituitary function can explain the observed subfertility phenotype. At present, few genes have been shown to be functionally required for uterine involution. It is concluded that AMPK plays a fundamental role in endometrial regeneration, maintenance of uterine histoarchitecture and fertility in the female.
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Details
- Title
- PRKAA1 and PRKAA2 are functionally required for endometrial regeneration following parturition and fertility in the female
- Creators
- Melissa Lyn McCallum
- Contributors
- James K. Pru (Degree Supervisor)
- Awarding Institution
- Washington State University
- Academic Unit
- Animal Sciences, Department of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University; [Pullman, Washington] :
- Identifiers
- 99900525171101842
- Language
- English
- Resource Type
- Thesis