Establishment and characterization of epithelial and fibroblast cell lines from the bovine endometrium

Berg, Malia D.; Chen, Ziting; Dean, Matthew

doi:10.1007/s11626-021-00640-z

Cited by 5 publications

(4 citation statements)

References 19 publications

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“…BUTE cells are an immortalized cell line generated from the luminal epithelium of a Holstein dairy cow. They have been shown to express keratin and lack vimentin by immunofluorescence, confirming their identity as a pure uterine epithelial cell population (Berg et al., 2022; Gonzalez et al., 2022). They respond to progesterone in other contexts (unpublished observations), but it is unknown if they respond to oxytocin.…”

Section: Methodsmentioning

confidence: 69%

“…One potential explanation for our results is that BUTE cells do not have a functional progesterone receptor. However, we have previously shown that BUTE cells express the progesterone receptor (Berg et al., 2022). Additionally, we have found that progesterone affects gene expression in BUTE cells via RNAseq, affecting expression of genes known to be regulated by progesterone such as SERPINE2 , SERPING1 , SULT1A1 and PRDX6 (unpublished observations).…”

Section: Discussionmentioning

confidence: 93%

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The glycogenolytic enzyme acid α‐glucosidase is expressed in the bovine uterine endometrium

Berg,

Dean

2024

Reprod Domestic Animals

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Progesterone has been shown to stimulate glycogen catabolism in uterine epithelial cells. Acid α‐glucosidase (GAA) is an enzyme that breaks down glycogen within lysosomes. We hypothesized that progesterone may stimulate glycogenolysis in the uterine epithelium via GAA. We found that GAA was more highly expressed in the stroma on Day 1 than on Day 11. However, GAA did not appear to differ in the epithelium on Days 1 and 11. Progesterone (0‐10 μM) had no effect on the levels of the full‐length inactive protein (110 kDa) or the cleaved (active) peptides present inside the lysosome (70 and 76 kDa) in immortalized bovine uterine epithelial (BUTE) cells. Furthermore, the activity of GAA did not differ between the BUTE cells treated with 10 μM progesterone or control. Overall, we confirmed that GAA is present in the cow endometrium and BUTE cells. However, progesterone did not affect protein levels or enzyme activity.

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Section: Methodsmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 93%

The glycogenolytic enzyme acid α‐glucosidase is expressed in the bovine uterine endometrium

Berg,

Dean

2024

Reprod Domestic Animals

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“…Obesity is associated with lower fertility in women receiving donated ova or serving as surrogates ( DeUgarte et al 2010 , Bellver et al 2013 ). Type 2 diabetes and obesity are associated with hyperinsulinemia, hyperglycemia, and other systemic changes in metabolism, any of which could contribute to uterine dysfunction ( Lathi et al 2005 , Khaliq et al 2020 , Berg et al 2022 ). In mice, diet-induced obesity dysregulates glycolysis in the endometrium, impairs decidualization, and reduces litter size ( Chen et al 2023 ).…”

Section: Maternal Metabolism and Fertilitymentioning

confidence: 99%

“…In agreement, estradiol stimulates the production of IGF1 in the uterine stroma, and a study showed that IGF1 increases glycogen levels in BUTE cells ( Cooke et al 1997 , Gonzalez et al 2022 ). Insulin has also been shown to increase glycogen levels in uterine epithelial cells ( Dean and Rose 2018 , Berg et al 2022 ). This might indicate that hyperinsulinemia increases uterine epithelial glycogen storage.…”

Section: Metabolism and Secretion Of Nutrients By The Uterine Epitheliummentioning

confidence: 99%

Endometrial glucose metabolism during early pregnancy

Chen,

Dean

2023

Reproduction and Fertility

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Approximately 50% of human pregnancies humans fail, most before or during implantation. One factor contributing to pregnancy loss is abnormal glucose metabolism in the endometrium. Glucose contributes to preimplantation embryo development, uterine receptivity, and attachment of the embryo. Across multiple species, the epithelium stores glucose as the macromolecule glycogen at estrus. This reserve is mobilized during the preimplantation period. Glucose from circulation or glycogenolysis can be secreted into the uterine lumen for use by the embryo or metabolized via glycolysis, producing ATP for the cell. The resulting pyruvate could be converted to lactate, another important nutrient for the embryo. Fructose is an important nutrient for early embryos, and the epithelium and placenta can convert glucose to fructose via the polyol pathway. The epithelium also uses glucose to glycosylate proteins, which regulates embryo attachment. In some species, decidualization of the stroma is critical to successful implantation. Formation of the decidua requires increased glucose metabolism via the pentose phosphate pathway and glycolysis. After decidualization, the cells switch to aerobic glycolysis to produce ATP. Paradoxically, the decidua also stores large amounts of glucose as glycogen. Too little glucose or an inability to take up glucose impairs embryo development and decidualization. Conversely, too much glucose inhibits these same processes. This likely contributes to the reduced pregnancy rates associated with conditions like obesity and diabetes. Collectively, precise control of glucose metabolism is important for several endometrial processes required to establish a successful pregnancy. The factors regulating these metabolic processes remain poorly understood.

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Progesterone increases metabolism via the pentose phosphate pathway in bovine uterine epithelial cells

Berg,

Braz,

Dean

2024

Mol Biol Rep

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Background During early pregnancy, glucose is essential for the uterine epithelium and the developing embryo. In cows, progesterone increases the secretion of glucose into the uterine lumen. The uterine epithelium can convert glucose to fructose, but other fates of glucose in the uterine epithelium have been sparsely investigated. Therefore, our objective was to investigate how progesterone influences glucose metabolism in immortalized bovine uterine epithelial (BUTE) cells. Methods BUTE cells were grown to 80% confluence and treated with vehicle (DMSO) or 10 µM progesterone for 24 h. Cells were collected and analyzed. Immunohistochemistry was performed on endometrial samples collected from the bovine endometrium on days 1 and 11 of the reproductive cycle. Results Progesterone treatment increased glucose consumption of BUTE cells. RNAseq identified 3,072 genes regulated by progesterone. KEGG analysis indicated that progesterone altered genes associated with metabolic pathways and glutathione metabolism. Manually examining genes unique to specific glucose metabolic pathways identified an increase in the rate-limiting enzyme in the pentose phosphate pathway—glucose-6-phosphate dehydrogenase. Functionally, a major product of the pentose phosphate pathway is NADPH, and progesterone treatment increased NADPH levels in BUTE cells. In cows, immunohistochemistry confirmed that glucose-6-phosphate dehydrogenase levels were higher in the uterine epithelium in the luteal phase when progesterone concentrations are high. Conclusions Progesterone increased glucose-6-phosphate dehydrogenase expression and metabolism via the pentose phosphate pathway in the bovine uterine epithelium. This metabolism could provide substrates for cell proliferation, molecules to be secreted into the uterine lumen, or maintain reduction/oxidation balance in the uterine epithelium. Supplementary Information The online version contains supplementary material available at 10.1007/s11033-024-10001-0.

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Establishment and characterization of epithelial and fibroblast cell lines from the bovine endometrium

Cited by 5 publications

References 19 publications

The glycogenolytic enzyme acid α‐glucosidase is expressed in the bovine uterine endometrium

The glycogenolytic enzyme acid α‐glucosidase is expressed in the bovine uterine endometrium

Endometrial glucose metabolism during early pregnancy

Progesterone increases metabolism via the pentose phosphate pathway in bovine uterine epithelial cells

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