Limits...
Folate Deficiency Could Restrain Decidual Angiogenesis in Pregnant Mice.

Li Y, Gao R, Liu X, Chen X, Liao X, Geng Y, Ding Y, Wang Y, He J - Nutrients (2015)

Bottom Line: It also showed a reduction in the expressions of VEGFA, VEGFR2, and PLGF.In addition, the serum levels of P4, E2, LH, and PRL were reduced in folate-deficient mice, and the expression of progesterone receptor (PR) and estrogen receptor α (ERα) were abnormal.These results indicated that folate deficiency could impaire decidual angiogenesis and it may be related to the vasculotoxic properties of Hcy and the imbalance of the reproductive hormone.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing 400016, China. colourful0324@yeah.net.

ABSTRACT
The mechanism of birth defects induced by folate deficiency was focused on mainly in fetal development. Little is known about the effect of folate deficiency on the maternal uterus, especially on decidual angiogenesis after implantation which establishes vessel networks to support embryo development. The aim of this study was to investigate the effects of folate deficiency on decidual angiogenesis. Serum folate levels were measured by electrochemiluminescence. The status of decidual angiogenesis was examined by cluster designation 34 (CD34) immunohistochemistry and the expression of angiogenic factors, including vascular endothelial growth factor A (VEGFA), placental growth factor (PLGF), and VEGF receptor 2 (VEGFR2) were also tested. Serum levels of homocysteine (Hcy), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone (P4), and estradiol (E2) were detected by Enzyme-linked immunosorbent assay. The folate-deficient mice had a lower folate level and a higher Hcy level. Folate deficiency restrained decidual angiogenesis with significant abnormalities in vascular density and the enlargement and elongation of the vascular sinus. It also showed a reduction in the expressions of VEGFA, VEGFR2, and PLGF. In addition, the serum levels of P4, E2, LH, and PRL were reduced in folate-deficient mice, and the expression of progesterone receptor (PR) and estrogen receptor α (ERα) were abnormal. These results indicated that folate deficiency could impaire decidual angiogenesis and it may be related to the vasculotoxic properties of Hcy and the imbalance of the reproductive hormone.

No MeSH data available.


Related in: MedlinePlus

Real-time polymerase chain reaction (RT-PCR) and western blot analysis of the expression of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), and placental growth factor (PLGF) from Embryonic day 6 (E6) to Embryonic day 8 (E8). (A) The mRNA levels of VEGFA, VEGFR2, and PLGF in folate-deficient mice were significantly decreased compared with normal mice from E6 to E8 (** p < 0.01). Data are presented as the mean ± standard error of the mean (SEM). (B) Protein levels in folate-deficient mice were compared with normal mice. Statistical analysis of protein expression was from three independent experiments (* p < 0.05). Data are presented as the mean ± SEM. (C) Western blot analysis of three angiogenic growth factors. β-actin was used as a loading control. The protein levels of VEGFA, VEGFR2, and PLGF showed similar trends to the mRNAs levels. N: normal group, FD: folate-deficient group.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4555123&req=5

nutrients-07-05284-f004: Real-time polymerase chain reaction (RT-PCR) and western blot analysis of the expression of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), and placental growth factor (PLGF) from Embryonic day 6 (E6) to Embryonic day 8 (E8). (A) The mRNA levels of VEGFA, VEGFR2, and PLGF in folate-deficient mice were significantly decreased compared with normal mice from E6 to E8 (** p < 0.01). Data are presented as the mean ± standard error of the mean (SEM). (B) Protein levels in folate-deficient mice were compared with normal mice. Statistical analysis of protein expression was from three independent experiments (* p < 0.05). Data are presented as the mean ± SEM. (C) Western blot analysis of three angiogenic growth factors. β-actin was used as a loading control. The protein levels of VEGFA, VEGFR2, and PLGF showed similar trends to the mRNAs levels. N: normal group, FD: folate-deficient group.

Mentions: Immunohistochemical staining for VEGFA, PLGF, and VEGFR2 in the decidual tissue on E8 is shown in Figure 3. VEGFA was distributed mainly in a wide area of the secondary decidual zone (PDZ) and embryo in both normal and folate-deficient mice, but the expression of VEGFA in folate-deficient mice was depressed (Figure 3A). VEGFR2 was localized mainly in the vascular sinus folding close to the anti-mesometrial region in normal mice, whereas VEGFR2 surrounded the embryo mainly in folate-deficient mice (Figure 3B). The localization of PLGF was similar to VEGFA in normal mice, but it did not distribute in the embryo. However, PLGF was mainly located in the central region of the uterus instead of the PDZ in folate-deficient mice (Figure 3C). The relative amounts of VEGFA, PLGF, and VEGFR2 mRNAs detected by real-time RT-PCR are shown in Figure 4A. The relative fold change of VEGFA, PLGF, and VEGFR2 mRNA in the folate-deficient mice was decreased compared with the levels in normal mice from E6 to E8 (p < 0.01). The protein expression levels of VEGFA, PLGF, and VEGFR2 analyzed by Western blotting were correlated with the level of mRNAs (Figure 4B).


Folate Deficiency Could Restrain Decidual Angiogenesis in Pregnant Mice.

Li Y, Gao R, Liu X, Chen X, Liao X, Geng Y, Ding Y, Wang Y, He J - Nutrients (2015)

Real-time polymerase chain reaction (RT-PCR) and western blot analysis of the expression of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), and placental growth factor (PLGF) from Embryonic day 6 (E6) to Embryonic day 8 (E8). (A) The mRNA levels of VEGFA, VEGFR2, and PLGF in folate-deficient mice were significantly decreased compared with normal mice from E6 to E8 (** p < 0.01). Data are presented as the mean ± standard error of the mean (SEM). (B) Protein levels in folate-deficient mice were compared with normal mice. Statistical analysis of protein expression was from three independent experiments (* p < 0.05). Data are presented as the mean ± SEM. (C) Western blot analysis of three angiogenic growth factors. β-actin was used as a loading control. The protein levels of VEGFA, VEGFR2, and PLGF showed similar trends to the mRNAs levels. N: normal group, FD: folate-deficient group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555123&req=5

nutrients-07-05284-f004: Real-time polymerase chain reaction (RT-PCR) and western blot analysis of the expression of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), and placental growth factor (PLGF) from Embryonic day 6 (E6) to Embryonic day 8 (E8). (A) The mRNA levels of VEGFA, VEGFR2, and PLGF in folate-deficient mice were significantly decreased compared with normal mice from E6 to E8 (** p < 0.01). Data are presented as the mean ± standard error of the mean (SEM). (B) Protein levels in folate-deficient mice were compared with normal mice. Statistical analysis of protein expression was from three independent experiments (* p < 0.05). Data are presented as the mean ± SEM. (C) Western blot analysis of three angiogenic growth factors. β-actin was used as a loading control. The protein levels of VEGFA, VEGFR2, and PLGF showed similar trends to the mRNAs levels. N: normal group, FD: folate-deficient group.
Mentions: Immunohistochemical staining for VEGFA, PLGF, and VEGFR2 in the decidual tissue on E8 is shown in Figure 3. VEGFA was distributed mainly in a wide area of the secondary decidual zone (PDZ) and embryo in both normal and folate-deficient mice, but the expression of VEGFA in folate-deficient mice was depressed (Figure 3A). VEGFR2 was localized mainly in the vascular sinus folding close to the anti-mesometrial region in normal mice, whereas VEGFR2 surrounded the embryo mainly in folate-deficient mice (Figure 3B). The localization of PLGF was similar to VEGFA in normal mice, but it did not distribute in the embryo. However, PLGF was mainly located in the central region of the uterus instead of the PDZ in folate-deficient mice (Figure 3C). The relative amounts of VEGFA, PLGF, and VEGFR2 mRNAs detected by real-time RT-PCR are shown in Figure 4A. The relative fold change of VEGFA, PLGF, and VEGFR2 mRNA in the folate-deficient mice was decreased compared with the levels in normal mice from E6 to E8 (p < 0.01). The protein expression levels of VEGFA, PLGF, and VEGFR2 analyzed by Western blotting were correlated with the level of mRNAs (Figure 4B).

Bottom Line: It also showed a reduction in the expressions of VEGFA, VEGFR2, and PLGF.In addition, the serum levels of P4, E2, LH, and PRL were reduced in folate-deficient mice, and the expression of progesterone receptor (PR) and estrogen receptor α (ERα) were abnormal.These results indicated that folate deficiency could impaire decidual angiogenesis and it may be related to the vasculotoxic properties of Hcy and the imbalance of the reproductive hormone.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing 400016, China. colourful0324@yeah.net.

ABSTRACT
The mechanism of birth defects induced by folate deficiency was focused on mainly in fetal development. Little is known about the effect of folate deficiency on the maternal uterus, especially on decidual angiogenesis after implantation which establishes vessel networks to support embryo development. The aim of this study was to investigate the effects of folate deficiency on decidual angiogenesis. Serum folate levels were measured by electrochemiluminescence. The status of decidual angiogenesis was examined by cluster designation 34 (CD34) immunohistochemistry and the expression of angiogenic factors, including vascular endothelial growth factor A (VEGFA), placental growth factor (PLGF), and VEGF receptor 2 (VEGFR2) were also tested. Serum levels of homocysteine (Hcy), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone (P4), and estradiol (E2) were detected by Enzyme-linked immunosorbent assay. The folate-deficient mice had a lower folate level and a higher Hcy level. Folate deficiency restrained decidual angiogenesis with significant abnormalities in vascular density and the enlargement and elongation of the vascular sinus. It also showed a reduction in the expressions of VEGFA, VEGFR2, and PLGF. In addition, the serum levels of P4, E2, LH, and PRL were reduced in folate-deficient mice, and the expression of progesterone receptor (PR) and estrogen receptor α (ERα) were abnormal. These results indicated that folate deficiency could impaire decidual angiogenesis and it may be related to the vasculotoxic properties of Hcy and the imbalance of the reproductive hormone.

No MeSH data available.


Related in: MedlinePlus