Adenosine Triphosphate Regresses Endometrial Explants in a Rat Model of Endometriosis

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Adenosine triphosphate reduced endometriotic explant size in rats while not affecting eutopic endometrial stromal cell proliferation.

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This paper investigated whether adenosine triphosphate (ATP) can regress endometrial explants in a rat model of endometriosis and whether ATP affects proliferation of eutopic endometrium stromal cells. After surgical induction of endometriosis, rats were treated with intragastric normal saline, gestrinone, ATP (3.4 mg/kg/d IG), or ATP (1.0 mg/kg/d intramuscular), and explant and eutopic uterine histology were assessed after four weeks; proliferation of human endometrial stromal hEM15A cells was measured over 24–72 hours using a CCK-8 assay. ATP administration increased explant regression compared with controls (notably higher regression in the intramuscular ATP group with similar pretreatment implant sizes), and epithelial preservation was better in saline than in ATP groups, while hEM15A proliferation showed no significant ATP-related difference versus controls. The paper does not explicitly address limitations in the abstract, but it relies on a small in vivo sample size (3 killed at baseline, with remaining rats split across groups) and an in vitro proliferation readout of a single stromal cell line. This paper is centrally about endometriosis—testing ATP’s ability to regress endometrial explants in a rat endometriosis model.

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Abstract

The aim of this study was to determine the effects of adenosine triphosphate (ATP) in a rat endometriosis model. After surgical induction of endometriosis, 3 rats were killed, and explants were measured in the remaining 19 rats, which were then randomly assigned to 4 groups. Group 1 (n = 4) received normal saline (2 mL/d intragastric [IG]), group 2 (n = 4) gestrinone (0.5 mg/kg/d IG), group 3 (n = 5) ATP (3.4 mg/kg/d IG), and group 4 (n = 6) ATP (1.0 mg/kg/d; intramuscularly), respectively. Four weeks after medication, they were euthanized to evaluate histological features of explants and eutopic uterine tissues. To test the effect of ATP on the growth of eutopic endometrium stromal cells, proliferation rates of hEM15A cells at 24, 48, and 72 hours after treatment with different concentrations of ATP and vehicle control were detected with the Cell Counting Kit-8 (CCK-8) method. There was a significant difference between pretreatment and posttreatment volumes within group 2 (positive control; P = .048) and group 4 (P = .044). On condition that pretreatment implant size was similar in both groups (P = .516), regression of explants in group 4 was significantly higher than that in group 1 (negative control; P = .035). Epithelial cells were significantly better preserved in group 1 than in group 3 (P = .008) and group 4 (P = .037). The CCK-8 assay showed no significant difference in proliferation among hEM15A cells treated with ATP and controls. These results suggest that ATP regresses endometriotic tissues in a rat endometriosis model but has no impact on the growth of eutopic endometrium stromal cells.
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Abstract

The aim of this study was to determine the effects of adenosine triphosphate (ATP) in a rat endometriosis model. After surgical induction of endometriosis, 3 rats were killed, and explants were measured in the remaining 19 rats, which were then randomly assigned to 4 groups. Group 1 (n = 4) received normal saline (2 mL/d intragastric [IG]), group 2 (n = 4) gestrinone (0.5 mg/kg/d IG), group 3 (n = 5) ATP (3.4 mg/kg/d IG), and group 4 (n = 6) ATP (1.0 mg/kg/d; intramuscularly), respectively. Four weeks after medication, they were euthanized to evaluate histological features of explants and eutopic uterine tissues. To test the effect of ATP on the growth of eutopic endometrium stromal cells, proliferation rates of hEM15A cells at 24, 48, and 72 hours after treatment with different concentrations of ATP and vehicle control were detected with the Cell Counting Kit-8 (CCK-8) method. There was a significant difference between pretreatment and posttreatment volumes within group 2 (positive control; P = .048) and group 4 (P = .044). On condition that pretreatment implant size was similar in both groups (P = .516), regression of explants in group 4 was significantly higher than that in group 1 (negative control; P = .035). Epithelial cells were significantly better preserved in group 1 than in group 3 (P = .008) and group 4 (P = .037). The CCK-8 assay showed no significant difference in proliferation among hEM15A cells treated with ATP and controls. These results suggest that ATP regresses endometriotic tissues in a rat endometriosis model but has no impact on the growth of eutopic endometrium stromal cells. Similar content being viewed by others

References

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Adenosine Triphosphate Regresses Endometrial Explants in a Rat Model of Endometriosis. Reprod. Sci. 23, 924–930 (2016). https://doi.org/10.1177/1933719115625847 Published: Issue date: DOI: https://doi.org/10.1177/1933719115625847

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endometriosis

MeSH descriptors

Adenosine Triphosphate Endometriosis Adenosine Triphosphate Animals Cell Line Cell Proliferation Disease Models, Animal Endometriosis Endometriosis Endometrium Endometrium Endometrium Female Humans Rats Rats, Sprague-Dawley Stromal Cells Stromal Cells Stromal Cells

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