Placental Effects of Systemic Tumour Necrosis Factor-α in an Animal Model of Gestational Diabetes Mellitus

被引:16
作者
Bobadilla, R. A. [1 ,2 ]
van Bree, R. [1 ]
Vercruysse, L. [1 ]
Pijnenborga, R. [1 ]
Verhaeghe, J. [1 ]
机构
[1] Katholieke Univ Leuven, Dept Obstet & Gynecol, B-3000 Leuven, Belgium
[2] Inst Politecn Nacl, Escuela Super Med, Mexico City 11340, DF, Mexico
关键词
Apoptosis; Gestational diabetes mellitus; TNF; Trophoblast invasion; Uterine natural killer cells; DIET-INDUCED OBESITY; METRIAL GLAND-CELLS; INSULIN-RESISTANCE; LEPR(DB/+) MICE; ADIPOSE-TISSUE; TNF-ALPHA; PREGNANCY; GROWTH; MOUSE; RAT;
D O I
10.1016/j.placenta.2010.09.017
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Gestational diabetes mellitus (GDM) may adversely affect fetoplacental interaction. Numerous reports demonstrate that GDM women have increased circulating tumour necrosis factor-alpha (TNF), a pro-apoptotic peptide. Objective: To examine whether implantation site apoptosis is increased by exogenous TNF in mice heterozygous for a defective leptin receptor (db/+), a GDm animal model. Study design: Implantation sites were studied at gestational day (gd)18.5 in 3 groups: saline-treated wild-type (wt) and db/+ mice, and TNF-treated db/+ mice. Saline or TNF (total dose 4 mu g) was administered by miniosmotic pump from gd11.5. Immunostaining for cleaved caspase-3,PAS and cytokeratin was performed for quantification of apoptotic cells, uterine natural killer (uNK) cells, and trophoblast invasion, respectively. The mRNA expression of TNF and TNF-induced apoptotic markers in placenta and mesometrial triangle (MT) was measured by quantitative RT-PCR. Results: The implantation sites from saline-treated wt and db/+ mice showed comparable numbers of apoptotic cells and uNK cells. Compared with the saline-treated groups, TNF-treated db/+ dams had less fetuses; the placental labyrinth and trophospongium contained more apoptotic cells; and the MT contained a higher total number of uNK cells including more cells intensely stained for cleaved caspase-3 as well as cells with negative staining. Trophoblast invasion was shallower in db/+ than in wt mice (14% and 30% of total invasion into MT, respectively) but this was not affected by TNF. The mRNA expression of TNF and apoptotic markers was comparable in the 3 groups. Conclusions: TNF treatment in dbl+ mice raises the number of apoptotic cells in the placenta, and appears to increase the retention of uNK cells in the MT. Db/+ mice demonstrate shallower trophoblast invasion which is unaffected by exogenous TNF. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1057 / 1063
页数:7
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