Changes in apoptosis and Bcl-2 expression in human hyperglycemic, term placental trophoblast

Apoptosis and its associated regulatory mechanisms are physiological events crucial to the maintenance of placental homeostasis; imbalance of these processes, however, such as occurs under various pathological conditions, may compromise placenta function and, consequently, pregnancy success. Increased apoptosis occurs in the placentas of pregnant women with several developmental disabilities, while increased Bcl-2 expression is generally associated with pregnancy-associated tumors. Herein, we tested the hypothesis that apoptosis-associated disturbs might be involved in the placental physiopathology subjected to different maternal hyperglycemic conditions.Thus, in the present study we investigated and compared the incidence of apoptosis using TUNEL reaction and Bcl-2 expression, in term-placentas of normoglycemic, diabetic and daily hyperglycemic patients. Tissue samples were collected from 37 placentas, being 15 from healthy mothers with normally delivered healthy babies, and 22 from mothers with glucose disturbances. From these latter 22 patients, 10 showed maternal daily hyperglycemia and 12 were clinically diabetics. Both Bcl-2 expression and apoptotic DNA fragmentation were established and quantified in the trophoblasts of healthy mothers. Compared to these reference values, a higher apoptosis index and lower Bcl-2 expression were disclosed in the placentas of the diabetic women, while in the daily hyperglycemic group, values were intermediate between the diabetic and normoglycemic patients. The TUNEL/Bcl-2 index ratio in the placentas varied from 0.02 to 0.09 for pregnant normoglycemic and diabetic women, respectively, revealing a predominance of apoptosis in the diabetic group. Our findings suggest that hyperglycemia may be a key factor evoking apoptosis in the placental trophoblast, and therefore, is relevant to diabetic placenta function. (c) 2006 Elsevier B.V.. All rights reserved.

BLOOD and PLACENTAL OXIDATIVE STRESS ASSESSMENT IN RATS WITH MILD DIABETES

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Histopathological placental lesions in mild gestational hyperglycemic and diabetic women

Objective: To investigate and compare the incidence of histopathological placental lesions in mild gestational hyperglycemia, gestational diabetes and overt diabetes at term and preterm gestation.Research design and methods: One-hundred-and-thirty-one placental samples were collected from Diabetes mellitus (DM) positive screened patients. Two diagnostic tests, glycemic profile and 100 g oral glucose tolerance test (OGTT) in parallel identified 4 groups normoglycemic, mild gestational hyperglycemia (MGH), gestational DM (GDM) or overt DM (DM). Placental tissue specimens and sections from 4 groups were obtained by uniform random sampling and stained with hematoxylin-eosin.Results: Placentas from MGH group presented 17 types of histopathological change and higher rates of syncytial nodes and endarteritis. GDM placentas presented only nine types of histopathological change, high rates of dysmaturity, low rates of calcification and no syncytial nodes. Overt DM placentas showed 22 types of histopathological change, 21 of which were present in the preterm period. There were histopathological similarities between MGH and DM placentas, but the former exhibited a higher incidence of endarteritis, which has been described as a post-mortem phenomenon.Conclusion: Our results confirmed that the distinct placental changes associated with DM and MGH depend on gestational period during which the diabetic insult occurs. It may reasonably be inferred that subclinical maternal hyperglycemia during pregnancy, as showed in MGH group, is responsible for increased placental endarteritis, a postmortem lesion in the live fetus.

Neonatally Induced Mild Diabetes in Rats and Its Effect on Maternal, Placental, and Fetal Parameters

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)