Thesis
Functional role of LIM domain binding protein 1 in murine female reproductive physiology and uterine hemoglobin biosynthesis
Washington State University
Master of Science (MS), Washington State University
05/2018
DOI:
https://doi.org/10.7273/000004232
Handle:
https://hdl.handle.net/2376/125063
Abstract
A large proportion, approximately 25-60%, of human conceptions fail to result in clinical pregnancy due to failure prior to placentation. Prior to placentation, the embryo relies solely upon diffusion of gases and nutrients from the maternal decidua for survival, a process that must be tightly regulated to promote proper embryonic development. Previous research has identified novel non-erythroid hemoglobin biosynthesis within both the human and murine uterus; however, the function and regulation of uterine-produced hemoglobin is only partly understood. Lim domain binding protein 1(Ldb1) is a transcriptional co-activator that is fundamentally required for hemoglobin biosynthesis in erythroid tissue and serves as a regulator of differentiation in a variety of tissues. The objective of this study was to evaluate the function of Ldb1 in murine fertility and production of uterine-derived hemoglobin. Conditional ablation of Ldb1 from the murine reproductive tract results in subfertility due to pre-mature reproductive senescence and increased offspring mortality rate. Aged Ldb1d/d female mice lack corporal lutea yet maintain all stages of folliculogenesis suggesting that the ablation of Ldb1 results in development of an age-dependent ovulation defect. Young nulliparous Ldb1d/d mice contain embryos with delayed development and decreased size and develop subtle abnormalities within the placental labyrinth layer despite no differences in maternal progesterone production. Furthermore, Ldb1d/d females fail to undergo artificial decidualization indicating that Ldb1 is required for uterine stromal cell differentiation. Uteri from Ldb1d/d females have decreased production of the hemoglobin-beta subunit (Hbb-bs_bt) and the heme biosynthetic enzyme delta-aminolevulinate synthase 2 (Alas2) at both the mRNA and protein level despite no changes in uterine vascularization. Evaluation of the function of Ldb1 within the murine reproductive tract has revealed that Ldb1 is required for proper function of multiple reproductive organs and its role in hemoglobin production is conserved in both erythroid and uterine tissue.
Metrics
2 File views/ downloads
17 Record Views
Details
- Title
- Functional role of LIM domain binding protein 1 in murine female reproductive physiology and uterine hemoglobin biosynthesis
- Creators
- Katriana Jorgensen-Muga
- Contributors
- JAMES K PRU (Advisor)
- 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
- Identifiers
- 99900896424301842
- Language
- English
- Resource Type
- Thesis