Trophoblast phagocytic program: roles in different placental systems

Although not belonging to the class of professional phagocytes, in many species trophoblast cells exhibit intense phagocytic activity. The complete range of physiological functions of trophoblast phagocytosis has not yet been fully characterized. Close association between the trophoblast and nutrition was determined many years ago. Hubrecht (1889) when proposing for the first time the name trophoblast to the external layer of the blastocyst, directly established the nutritive significance of this embryonic layer. Indeed, histotrophic phagocytosis, i.e. the internalization of maternal cells and secreted materials, is considered an important function of the trophoblast before the completion of the placenta. Recently, however, unexpected characteristics of the trophoblast have significantly enhanced our understanding of this process. Roles in acquisition of space for embryo development, in tissue remodeling during implantation and placentation and in defense mechanisms are highlighting how this cellular activity may be relevant for the maternal-fetal relationship beyond its nutritional function.

Inhibition of Trypanosoma brucei glucose-6-phosphate dehydrogenase by human steroids and their effects on the viability of cultured parasites

Dehydroepiandrosterone ( DHEA) is known as an intermediate in the synthesis of mammalian steroids and a potent uncompetitive inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH), but not the enzyme from plants and lower eukaryotes. G6PDH catalyzes the first step of the pentose-phosphate pathway supplying cells with ribose 5-phosphate, a precursor of nucleic acid synthesis, and NADPH for biosynthetic processes and protection against oxidative stress. In this paper we demonstrate that also G6PDH of the protozoan parasite Trypanosoma brucei is uncompetitively inhibited by DHEA and epiandrosterone (EA), with K(i) values in the lower micromolar range. A viability assay confirmed the toxic effect of both steroids on cultured T. brucei bloodstream form cells. Additionally, RNAi mediated reduction of the G6PDH level in T. brucei bloodstream forms validated this enzyme as a drug target against Human African Trypanosomiasis. Together these findings show that inhibition of G6PDH by DHEA derivatives may lead to the development of a new class of anti-trypanosomatid compounds. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.

Steroidogenesis in cumulus cells of bovine cumulus-oocyte-complexes matured in vitro with BSA and different concentrations of steroids

The present in vitro experiments were designed to evaluate the ability of bovine cumulus-oocyte-complexes (COCs)to produce steroids and also to evaluate the modulatory effects of added estradiol, progesterone and testosterone on the steroidogenic activity of COCs. Considerable estradiol accumulation was observed in the control maturation medium for in vitro maturation of bovine COCs during the 24h of maturation (P < 0.05). When testosterone was added to the medium at various concentrations, a slight estradiol accumulation occurred, which, however, was lower (P < 0.05) than that observed in the control medium. Slight estradiol accumulation was observed in maturation medium containing progesterone at concentrations of 2.5, 5.0 and 10.0 mug/ml, but these increases were less (P < 0.05) than those observed in the control medium. However, in the presence of 1.0 mug/ml progesterone, estradiol accumulation was equal to that of the control medium (P > 0.05). Progesterone accumulation (P < 0.05) was observed in the control medium for in vitro maturation of bovine COCs. When estradiol was added to the maturation medium, progesterone accumulation was observed, but was significant (P < 0.05) only when the medium was supplemented with the lesser concentrations of estradiol utilized in the experiment (1.0 mug/ml). The results demonstrated that (1) cumulus cells of bovine COCs are able to secrete estradiol and progesterone in culture systems for in vitro maturation, and this steroidogenesis is modulated by the steroids progesterone, testosterone and estradiol, and (2) the addition of estradiol to the in vitro maturation medium of bovine oocytes should be reviewed, since cumulus cells of COCs have been demonstrated to secrete estradiol in the maturation medium. (C) 2002 Elsevier B.V. B.V. All rights reserved.

Gonadal steroids levels and vitellogenesis in the formation of oocytes in Prochilodus lineatus (Valenciennes) (Teleostei: Characiformes)

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

Evaluation of placental glycogen storage in mild diabetic rats

Purpose: To evaluate the placental glycogen storage and fetal development in the pregnancy of neonatally streptozocin-induced diabetic rats and to establish relation with glycemia and insulin levels. Methods: At the birth day, 147 female rats were randomly distributed in two experimental groups: 1) Non-diabetic Group (Control, n=45) - received the vehicle; 2) Diabetic Group (STZ, n=102) received 100 mg streptozocin/kg in neonatal period. At day 0 of pregnancy, adult female rats were included in the control group when presented glycemia below 120 mg/dL and, in the group STZ with glycemia between 120 and 300 mg/dL. At day 21 of pregnancy, blood samples were collected for glycemia and insulin determination, and placentas withdrawn for placental glycogen determination. The newborns (NB) were classified in small (SGA), appropriate (AGA) and large (LGA) for gestational age. Results: Rats STZ presented higher glycemia at days 0 and 14 of pregnancy. At end of pregnancy, rats STZ showed higher proportion of NB SGA and LGA; reduced rate of NB AGA and unaltered glycemia, insulin and placental glycogen determinations. Conclusion: Mild diabetes altered the maternal glycemia in the early pregnancy, impairing future fetal development, but it caused no alteration on insulin and placental glycogen determination, confirming that this glycemic intensity was insufficient to change glycogen metabolism.

Plasma concentrations and placental immunostaining of interleukin-10 and tumor necrosis factor-alpha as predictors of alterations in the embryo-fetal organism and the placental development of diabetic rats

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

Morphometric study of placental villi and vessels in women with mild hyperglycemia or gestational or overt diabetes

In this study, morphometric measures of placental terminal villi and villous vessels were compared in overt, as well as gestational diabetes mellitus, and mild hyperglycemia diagnosed by oral 100 g glucose tolerance test (100 g-OGTT) and glucose profile (GP). At delivery (gestational age >= 34 weeks) a total of 207 placentas were assigned to a control group (n = 56) or to one of three groups complicated by mild hyperglycemia (n = 5 1), gestational diabetes (n = 59) and overt diabetes (n = 4 1). Placenta samples were randomly selected for blind morphometric assessment with an image analyser. Morphometric measures obtained included area and number of terminal villi and their respective villous vessels. Statistical analyses were performed using the chi-square test, ANOVA and stepwise regression (p <= 0.05). Glycemic means were 86.2 mg/dL in controls, 98.9 mg/dL in mild hyperglycemia, 114.1 mg/dL in gestational diabetes and 122.1 mg/dL in overt diabetes. Our results show that abnormal maternal glycemic levels may change the placental morphometric characteristics related to materno-fetal exchanges. (C) 2007 Elsevier B.V.. All rights reserved.

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.