TY - JOUR
T1 - Placental Effects of Systemic Tumour Necrosis Factor-α in an Animal Model of Gestational Diabetes Mellitus
AU - Bobadilla, R. A.
AU - Van Bree, R.
AU - Vercruysse, L.
AU - Pijnenborg, R.
AU - Verhaeghe, J.
N1 - Funding Information:
This work was supported by grant no. G.0285.07 from the Fonds voor Wetenschappelijk Onderzoek (FWO)-Vlaanderen (Belgium) . The FWO did not interfere with any part of the study. R.A. Bobadilla was a senior scientist on sabbatical leave from the Escuela Superior de Medicina del Instituto Politécnico Nacional (Mexico), and was partly supported by ICYTDF and COFAA (Mexico).
PY - 2010/12
Y1 - 2010/12
N2 - Background: Gestational diabetes mellitus (GDM) may adversely affect fetoplacental interaction. Numerous reports demonstrate that GDM women have increased circulating tumour necrosis factor-α (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 μg) 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 db/+ 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.
AB - Background: Gestational diabetes mellitus (GDM) may adversely affect fetoplacental interaction. Numerous reports demonstrate that GDM women have increased circulating tumour necrosis factor-α (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 μg) 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 db/+ 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.
KW - Apoptosis
KW - Gestational diabetes mellitus
KW - TNF
KW - Trophoblast invasion
KW - Uterine natural killer cells
UR - http://www.scopus.com/inward/record.url?scp=78649449864&partnerID=8YFLogxK
U2 - 10.1016/j.placenta.2010.09.017
DO - 10.1016/j.placenta.2010.09.017
M3 - Artículo
SN - 0143-4004
VL - 31
SP - 1057
EP - 1063
JO - Placenta
JF - Placenta
IS - 12
ER -