Diabetes (db/db) mutation-induced endometrial epithelial lipoapoptosis: ultrastructural and cytochemical analysis of reproductive tract atrophy
Open accessAbstract
BACKGROUND: The diabetes (db/db) mutation in C57BL/KsJ mice promotes a progressive cytolipidemia within the endometrial epithelial (EE) layer of the female reproductive tract which results in premature cellular and organ atrophy. The current studies focus on the ultrastructural and cytochemical changes which promote nuclear apoptosis and cytostructural disruption following the expression of endometrial hypercytolipidemia which promotes diabetes-associated organoinvolution and manifest infertility. METHODS: Control (normal:+/+) and diabetes (db/db) genotype groups were prepared for high resolution light microscopic analysis of cytolipidemia and nuclear apoptosis (TUNEL-labeled 3'-DNA fragmentation) indices and compared to the transmission electron (TEM) microscopic analysis of endometrial tissue samples collected from 8-16 week-old groups. RESULTS: Compared to controls, db/db mutation expression induced a dramatic increase in EE cytolipid vacuole volume and density within the epithelial endometrial layer. TEM analysis revealed that cytolipid vacuole accumulations initially aggregated at the baso-polar regions of UEE cells in response to the systemic hyperglycemic/hypertriglyceridemic conditions which characterized the (db/db) groups. Progressive cytoplasmic movement of the lipid pools into perinuclear compartments of affected EE cells induced nuclear isolation from organelles that were displaced towards peripheral cytoplasmic compartments. Cytochemical analysis of lipid vacuole accumulations indicated attraction towards, and incorporation within, the nuclear envelope of hyperlipidemic cells. Co-localization of nuclear apoptotic 3'-DNA fragments within identified hyperlipidemic EE cells was coincident with the cytochemical and ultrastructural identification of lipid penetration through the nuclear envelope in db/db mutants. CONCLUSION: These results are the first cytochemical indication that the metabolic disturbances in db/db mutants which promote hypercytolipidemia are coincident with lipoapoptosis-induced nuclear dissolution, as denoted by DNA fragmentation analysis. The lipidemia-induced alterations in intracellular organelle and nuclear architectures suggests that the metabolic disturbances in glucose and lipid metabolic cascades in diabetes (db/db) mutants disrupts cytointegrity, culminating in nuclear disregulation (as indicated by lipoapoptosis) and eventual premature reproductive tract organoinvolution and resultant, manifest, reproductive sterility.
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Some animal models have demonstrated that GLP1 might have a direct impact on the hypothalamus-pituitary-testicular axis beyond weight reduction.
“Furthermore, some animal models have demonstrated that GLP1 might even have a direct impact on HPT that is beyond WR (10, 11, 12, 13, 14).”
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- Authors
- Garris, D. R.
- Affiliations
- University of Missouri–Kansas City (US)
- Corresponding author
- Garris, David R
- Venue
- Reproductive Biology and Endocrinology
- Published
- 2005-04-27
- Volume
- 3
- Issue
- 1
- Pages
- 15-15
- ISSN
- 1477-7827 (ISSN-L)
- PMC
- PMC1097758
- OpenAlex
- W2141930962
- Cited by
- 19
- References
- 27
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2021: 1 · 2019: 3 · 2018: 2 · 2017: 1 · 2015: 1 · 2014: 4 · 2013: 1 · 2012: 1
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Reproductive Biology and Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MOspace Institutional Repository (University of Missouri) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Universidad de Especialidades Espíritu Santo
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Agricultural and Biological Sciences › Agronomy and Crop Science › Reproductive Physiology in Livestock
- Keywords
- db/db mice, type 2 diabetes, endometrial epithelium, lipoapoptosis, DNA fragmentation, nuclear envelope, lipid vacuoles, infertility, hypertriglyceridemia, hyperglycemia, ultrastructure
- MeSH terms
- Animals, Atrophy, Diabetes Mellitus, Type 2, Endometrium, Epithelial Cells, Female, Hyperglycemia, Mice, Obese, Models, Biological, Mutation, Phenotype, Uterine Diseases, Apoptosis, Genetic Predisposition to Disease, Microscopy, Electron, Transmission, Diabetes Complications, Lipid Metabolism, Mice
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