Contribution of the immune system to follicle differentiation, ovulation and early corpus luteum formation

Abdulrahman, Noof; Fair, Trudee

doi:10.21451/1984-3143-ar2019-0087

Cited by 10 publications

(6 citation statements)

References 110 publications

(98 reference statements)

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“…The complement system is involved in the innate immune system and mostly functions to remove pathogens, dead cells, and debris. During early pregnancy there are changes to immune cells and markers in the endometrium (75,76). In ruminants, receptivity to implantation involves a set of orchestrated events, among which is the suppression of genes for immune recognition of the conceptus (embryo/ fetus and associated membranes) and the increase in vascularization of the endometrium (reviewed by (77)).…”

Section: Discussionmentioning

confidence: 99%

Endometrium On-a-Chip Reveals Insulin- and Glucose-induced Alterations in the Transcriptome and Proteomic Secretome

Tinning

Vasconcelos

et al. 2021

Endocrinology

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The molecular interactions between the maternal environment and the developing embryo that are key for early pregnancy success and are influenced by factors such as maternal metabolic status. Our understanding of the mechanism(s) through which these individual nutritional stressors alter endometrial function and the in utero environment for early pregnancy success is, however, limited. Here we report, for the first time, the use of an endometrium-on-a-chip microfluidics approach to produce a multi-cellular endometrium in vitro. Isolated endometrial cells (epithelial and stromal) from the uteri of non-pregnant cows in the early-luteal phase (Day 4-7), were seeded in the upper chamber of the device (epithelial cells; 4-6 10 4 cells/mL) and stromal cells seeded in the lower chamber (1.5-2 10 4 cells/mL). Exposure of cells to different concentrations of glucose (0.5, 5.0 or 50 mM) or insulin (Vehicle, 1 or 10 ng/mL) were performed at a flow rate of 1µL/min for 72 hr. Quantitative differences in the cellular transcriptome and the secreted proteome of in vitro-derived uterine luminal fluid (ULF) were determined by RNA-sequencing and Tandem Mass Tagging Mass Spectrometry (TMT-MS), respectively. High glucose concentrations altered 21 and 191 protein-coding genes in epithelial and stromal cells, respectively (p<0.05), with a dose-dependent quantitative change in the protein secretome (1 and 23 proteins). Altering insulin concentrations resulted in limited transcriptional changes including transcripts for insulin-like binding proteins that were cell specific but altered the quantitative secretion of 196 proteins. These findings highlight one potential mechanism by which changes to maternal glucose and insulin alter uterine function.

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Section: Discussionmentioning

confidence: 99%

Endometrium On-a-Chip Reveals Insulin- and Glucose-induced Alterations in the Transcriptome and Proteomic Secretome

Tinning

Vasconcelos

et al. 2021

Endocrinology

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“…The complement system involved in the innate immune system and mostly functions to remove pathogens, dead cells, and debris. During early pregnancy there are changes to immune cells and markers in the endometrium (67, 68). In ruminants, receptivity to implantation involves a set of orchestrated events, among which the suppression of genes for immune recognition of the conceptus (embryo/fetus and associated membranes) and the increase in vascularization of the endometrium (Reviewed by (69)).…”

Section: Discussionmentioning

confidence: 99%

Endometrium-on-a-chip reveals the endometrial transcriptome, and protein content of secretome are altered by changes in circulating concentrations of insulin and glucose in vitro

Thc

Tinning

Ejr

et al. 2020

Preprint

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The molecular interactions between the maternal environment and developing embryo that are key for early pregnancy success are known to be influenced by factors such as the metabolic status. We are, however, limited in our understanding of the mechanism by which these individual nutritional stressors alter endometrial function and the in utero environment for early pregnancy success. Here we report for the first time the use of endometrium-on-a-chip microfluidics approach to produce a multi-cellular endometrium in vitro, that is exposed to glucose and insulin concentrations associated with maternal metabolic stressors. Following isolation of endometrial cells (epithelial and stromal) from the uteri of non-pregnant cows in early-luteal phase (Day 4-7 approximately) epithelial cells were seeded into the upper chamber (4-6 104 cells/mL) and stromal cells seeded in the lower chamber (1.5-2 104 cells/mL). Three different concentration of glucose 1) 0.5 mM 2) 5.0 mM or 3) 50.0 mM or insulin 1) Vehicle, 2) 1.0 ng/mL or 3) 10.0 ng/mL were performed in the endometrial cells at a flow rate of 1uL/min for 72 hr to mimic the rate of secretion in vivo. Quantitative differences in the transcriptomic response of the cells and the secreted proteome of in vitro-derived uterine luminal fluid (ULF) were determined by RNA-sequencing and TMT respectively. Changes in maternal glucose altered 21 and 191 protein coding genes in epithelial and stromal cells respectively (p<0.05). While there was a dose-dependent quantitative change in protein secretome (1 and 23 proteins). Insulin resulted in limited transcriptional changes including insulin-like binding proteins that were cell specific (5, 12, and 20) but altered the quantitative secretion of 196 proteins including those involved in extracellular matrix-receptor interaction and proteoglycan siganlinng in cancer. Collectively, these highlight the potential mechanism by which changes to maternal glucose and insulin alter uterine function.

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“…Macrophages are the most abundant immune cells within the ovary and significantly increase in number in the developing corpus luteum [101,102]. Progressive macrophage ablation increases the amount of ovarian hemorrhage in luteal and thecal tissue due to significant endothelial cell depletion and erythrocyte accumulation [103].…”

Section: Role Of Macrophages On Angiogenesis Of the Ovarian Corpus Lu...mentioning

confidence: 99%

Immune and vascular contributions to organogenesis of the testis and ovary

DeFalco

2021

The FEBS Journal

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Contribution of the immune system to follicle differentiation, ovulation and early corpus luteum formation

Cited by 10 publications

References 110 publications

Endometrium On-a-Chip Reveals Insulin- and Glucose-induced Alterations in the Transcriptome and Proteomic Secretome

Endometrium On-a-Chip Reveals Insulin- and Glucose-induced Alterations in the Transcriptome and Proteomic Secretome

Endometrium-on-a-chip reveals the endometrial transcriptome, and protein content of secretome are altered by changes in circulating concentrations of insulin and glucose in vitro

Immune and vascular contributions to organogenesis of the testis and ovary

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