Selective Apoptosis of Luteal Endothelial Cells in Dexamethasone-Treated Rats Leads to Ischemic Necrosis of Luteal Tissue1

Gaytán, Francisco; Morales, C.; Bellido, C. Bernal; Sánchez-Criado, José E.

doi:10.1095/biolreprod66.1.232

Cited by 28 publications

(14 citation statements)

References 45 publications

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“…In human P. falciparum malaria, heparin (21), anti-TNF-␣ antibodies (52), and pentoxifylline (24,35) have failed to provide any therapeutic benefit, while dexamethasone (which is known to induce endothelial apoptosis in vivo [15,53]) was even deleterious (25,54). Activated or apoptotic endothelial cells become procoagulant, reflected by decreased protein C and elevated plasma thrombin-antithrombin III levels in P. falciparum malaria (5,22,44).…”

Section: Discussionmentioning

confidence: 99%

Plasmodium falciparumMalaria: Reduction of Endothelial Cell Apoptosis In Vitro

Hemmer

Lehr²,

Westphal

et al. 2005

Infect Immun

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Organ failure in Plasmodium falciparum malaria is associated with neutrophil activation and endothelial damage. This study investigates whether neutrophil-induced endothelial damage involves apoptosis and whether it can be prevented by neutralization of neutrophil secretory products. Endothelial cells from human umbilical veins were coincubated with neutrophils from healthy donors and with sera from eight patients with P. falciparum malaria, three patients with P. vivax malaria, and three healthy controls. Endothelial apoptosis was demonstrated by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) and annexin V staining. The rate of apoptosis of cells was markedly increased after incubation with patient serum compared to that with control serum. Apoptosis was most pronounced after incubation with sera from two patients with fatal cases of P. falciparum malaria, followed by sera of survivors with severe P. falciparum malaria and, finally, by sera of patients with mild P. falciparum and P. vivax malaria. Ascorbic acid, tocopherol, and ulinastatin reduced the apoptosis rate, but gabexate mesilate and pentoxifylline did not. Furthermore, in fatal P. falciparum malaria, apoptotic endothelial cells were identified in renal and pulmonary tissue by TUNEL staining. These findings show that apoptosis caused by neutrophil secretory products plays a major role in endothelial cell damage in malaria. The antioxidants ascorbic acid and tocopherol and the protease inhibitor ulinastatin can reduce malaria-associated endothelial apoptosis in vitro.

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Section: Discussionmentioning

confidence: 99%

Plasmodium falciparumMalaria: Reduction of Endothelial Cell Apoptosis In Vitro

Hemmer

Lehr²,

Westphal

et al. 2005

Infect Immun

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“…The ovary expresses glucocorticoid receptor (GR) and direct action of glucocorticoid on various ovarian functions has been reported in several species (Hsueh & Erickson 1978, Luck 1988, Fitzpatrick & Richards 1991, Kawate et al 1993, Urban et al 1994, Spicer & Chamberlain 1998, Gaytan et al 2002, Yang et al 2002. The ovary does not produce glucocorticoid per se and the access of active glucocorticoid (i.e.…”

Section: Introductionmentioning

confidence: 99%

Expression of 11beta-hydroxysteroid dehydrogenases in bovine follicle and corpus luteum

Tetsuka¹,

Yamamoto²,

Hayashida³

et al. 2003

Journal of Endocrinology

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In glucocorticoid target organs, local concentrations of active glucocorticoid are determined by the relative expression of two 11 -hydroxysteroid dehydrogenases (HSDs): bi-directional 11 -HSD type1 (11HSD1) that mainly activates cortisone to cortisol, and dehydrogenase 11 -HSD type2 (11HSD2) that inactivates cortisol to cortisone. In this study, we examined the expression of mRNA encoding these two 11 -HSDs in bovine granulosa cells harvested from preovulatory follicles and corpora lutea (CL). Ovaries were obtained from Holstein cows at a local slaughterhouse. Follicles larger than 10 mm in diameter and CL were dissected and follicular fluid and granulosa cells were taken. Corpora lutea were weighed and their stages were morphologically assessed (stage I, days 1-4; stage II, days 5-10; stage III, days 11-17; stage IV, days 8-20). Follicles were classified into four groups according to their hormonal status (oestradiol (E 2 ): progesterone (P 4 )>1: oestrogen active; E 2 :P 4 <1: oestrogen inactive) and stage of the oestrous cycle (luteal or follicular phase). Total RNA was extracted with phenol-chloroform and subjected to a semi-quantitative RT-PCR for 11HSD1, 11HSD2 and -actin. Concentrations of steroids in follicular fluid were determined by an enzyme immunoassay. In granulosa cells, only 11HSD1 mRNA was detected. There was a negative correlation between the expression of 11HSD1 and the concentration of cortisol in follicular fluid (P<0·05), indicating 11HSD1 may act as a dehydrogenase in the bovine follicle. Both types of 11 -HSDs were expressed in CL. The levels of mRNA for both isozymes were high in stage I and II, and were decreased in stage III CL. In stage IV CL, the expression of 11HSD2 but not 11HSD1 mRNA increased. These results indicate that the bovine granulosa cells and CL express 11HSD1 and 11HSD2, and they may play an important physiological role in the bovine ovary through modulating the local glucocorticoid environment.

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“…In conclusion, although luteolysis is associated with early deletion of the endothelium in some species (Azmi & O'Shea 1984, Sawyer et al 1990, Modlich et al 1996, Gaytan et al 2002, there is no evidence that endothelial cell death is the trigger for naturally occurring luteolysis in the mare, because we have established that the death of both endothelial and hormone-producing cells is temporally associated. However, this does not exclude the possibility that inducing selective regression of the immature vasculature could trigger functional and structural luteolysis as a result of decreased blood supply.…”

Section: Discussionmentioning

confidence: 57%

“…This suggests that in domestic species, in which structural luteolysis is brought about by endogenous uterine PG, the endothelial cell death plays a major role in the luteolytic cascade. By contrast in primates, where there is no endogenous luteolysin, luteolysis is a relatively protracted event involving predominantly non-apoptotic mechanisms (Fraser et al 1999) or necrosis of other luteal cells (Gaytan et al 2002), and in which apoptosis of endothelial cells is less apparent.…”

Section: Discussionmentioning

confidence: 98%

“…At the end of the luteal phase, the release of PGF-2a causes a dramatic decrease in plasma progesterone, which is defined as functional luteolysis and precedes structural regression of the CL (Douglas & Ginther 1972, 1976, Henderson & McNatty 1975. A distinct sequence of events is associated with the demise of the CL, including changes in blood supply (Miyamoto et al 2005), infiltration of leucocytes (Bukovsky et al 1995, Gaytan et al 1998, and death of steroidogenic and endothelial cells by both apoptotic (Juengel et al 1993, McCormack et al 1998) and non-apoptotic mechanisms (Fraser et al 1999, Morales et al 2000, Gaytan et al 2002. However, the mechanisms involved in regression of luteal tissue in the mare are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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Temporal relationship between proliferating and apoptotic hormone-producing and endothelial cells in the equine corpus luteum

Aguilar¹,

Fraser²,

Wilson³

et al. 2006

Reproduction

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The temporal relationship between endothelial cell death, vascular regression and the death of hormone-producing cells in the mare has not been established. To determine the dynamics of cell proliferation and death throughout the luteal phase, corpora lutea were studied at the early, mid-and late luteal phase, and after treatment with cloprostenol in the mid-luteal phase to induce premature luteolysis. Changes in cell proliferation and apoptosis were investigated utilising specific markers (phosphorylated histone-3 and activated caspase-3 respectively). Histone-3 positive cells were most abundant during the early luteal phase, and were mainly present in endothelial cells. Histone-3 activity significantly increased in hormone-producing cells 36 h after cloprostenol treatment. Frequency of activated caspase-3 staining peaked on day 14, and was induced by 36 h after cloprostenol administration in mid-luteal phase. However, cell death occurred simultaneously in the endothelial and hormone-producing cells. These results show that a subset of hormone-producing cells enter the early stages of cell division around luteolysis, while the majority of cells are undergoing cell death. Natural and induced functional and structural luteal regression in the mare can be at least partially attributed to simultaneous apoptosis of endothelial and hormone-producing cells. However, there is no evidence that endothelial cell death is the trigger for naturally occurring luteolysis.

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Selective Apoptosis of Luteal Endothelial Cells in Dexamethasone-Treated Rats Leads to Ischemic Necrosis of Luteal Tissue1

Cited by 28 publications

References 45 publications

Plasmodium falciparumMalaria: Reduction of Endothelial Cell Apoptosis In Vitro

Plasmodium falciparumMalaria: Reduction of Endothelial Cell Apoptosis In Vitro

Expression of 11beta-hydroxysteroid dehydrogenases in bovine follicle and corpus luteum

Temporal relationship between proliferating and apoptotic hormone-producing and endothelial cells in the equine corpus luteum

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