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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

Immunohistochemistry staining with cluster designation 34 (CD34) from Embryonic day 6 (E6) to Embryonic day 8 (E8). Impaired formation of decidual angiogenesis was detected in the folate-deficient group. The pictures in the right column are the higher magnification images of the black boxes in the left column. (A) The magnified area was the central region around the embryo in uterus at E6. (B, C) The magnified area was one side of VSF at E7 and E8. Arrow indicates the variable-sized blood vessels. N: normal group; FD: folate-deficient group; E: embryo; L: luminal epithelium; G: glandular epithelium; M: mesometrial; AM: anti-mesometrial; VSF: vascular sinus folding. Scale bar: 500 μm (left), 100 μm (right).
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nutrients-07-05284-f002: Immunohistochemistry staining with cluster designation 34 (CD34) from Embryonic day 6 (E6) to Embryonic day 8 (E8). Impaired formation of decidual angiogenesis was detected in the folate-deficient group. The pictures in the right column are the higher magnification images of the black boxes in the left column. (A) The magnified area was the central region around the embryo in uterus at E6. (B, C) The magnified area was one side of VSF at E7 and E8. Arrow indicates the variable-sized blood vessels. N: normal group; FD: folate-deficient group; E: embryo; L: luminal epithelium; G: glandular epithelium; M: mesometrial; AM: anti-mesometrial; VSF: vascular sinus folding. Scale bar: 500 μm (left), 100 μm (right).

Mentions: To determine whether there was any abnormal angiogenesis in the folate-deficient group, the structural changes in blood vessels, the molecular regulation of angiogenesis, and the vascular remodeling in the uterus were analyzed from E6 to E8, which was after implantation (E4–5) but prior to initial placenta establishment (E9–10). As illustrated in the H&E staining, no obvious abnormalities could be seen in the folate-deficient group (Figure 1). With the development of the process of pregnancy, there was no significant difference in morphology and structure in the two groups. In the folate-deficient mice, the blastocyst could implant in the mesangial contralateral visibly. Stroma cell decidulization occurred around the blastocyst continuously and formed the primary decidual zone and secondary decidual zone gradually. The development of the blastocyst was normal as well. However, the significant abnormalities were observed in the vascular density and the enlargement and elongation of vascular sinus folding in folate-deficient pregnant mice, as evidenced with CD34 staining from E6 to E8 (Figure 2). Normally, variable-sized vascular sinus foldings [21] are distributed symmetrically in the central region of the uterus and are enlarged and elongated over time, whereas fine mesh-like blood vessels are arrayed in the anti-mesometrial region, which was similar to our findings (Figure 2). Closer observation of the central region revealed that the sprouting process was most active at E6 (Figure 2A), whereas enlargement and elongation of vascular sinus folding and intussusception of blood vessels [22] were dominant from E7 to E8. Time-series analyses indicated that, compared with E6, the number of large-sized vascular sinus foldings in the central region as well as blood vessel densities in the anti-mesometrial region were markedly increased at E7 and E8 (Figure 2B,C). A significant decrease in vascular density was observed in the folate-deficient group from E6 to E8 as compared with the normal group (Figure 2). The vascular sinus foldings, which predominantly extend into the intermediate zone from the mesometrial to the anti-mesometrial region of the decidua, appeared to be diminished in the folate-deficient group as compared with the normal group, especially at E7 and E8 (Figure 2B,C).


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)

Immunohistochemistry staining with cluster designation 34 (CD34) from Embryonic day 6 (E6) to Embryonic day 8 (E8). Impaired formation of decidual angiogenesis was detected in the folate-deficient group. The pictures in the right column are the higher magnification images of the black boxes in the left column. (A) The magnified area was the central region around the embryo in uterus at E6. (B, C) The magnified area was one side of VSF at E7 and E8. Arrow indicates the variable-sized blood vessels. N: normal group; FD: folate-deficient group; E: embryo; L: luminal epithelium; G: glandular epithelium; M: mesometrial; AM: anti-mesometrial; VSF: vascular sinus folding. Scale bar: 500 μm (left), 100 μm (right).
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Related In: Results  -  Collection

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nutrients-07-05284-f002: Immunohistochemistry staining with cluster designation 34 (CD34) from Embryonic day 6 (E6) to Embryonic day 8 (E8). Impaired formation of decidual angiogenesis was detected in the folate-deficient group. The pictures in the right column are the higher magnification images of the black boxes in the left column. (A) The magnified area was the central region around the embryo in uterus at E6. (B, C) The magnified area was one side of VSF at E7 and E8. Arrow indicates the variable-sized blood vessels. N: normal group; FD: folate-deficient group; E: embryo; L: luminal epithelium; G: glandular epithelium; M: mesometrial; AM: anti-mesometrial; VSF: vascular sinus folding. Scale bar: 500 μm (left), 100 μm (right).
Mentions: To determine whether there was any abnormal angiogenesis in the folate-deficient group, the structural changes in blood vessels, the molecular regulation of angiogenesis, and the vascular remodeling in the uterus were analyzed from E6 to E8, which was after implantation (E4–5) but prior to initial placenta establishment (E9–10). As illustrated in the H&E staining, no obvious abnormalities could be seen in the folate-deficient group (Figure 1). With the development of the process of pregnancy, there was no significant difference in morphology and structure in the two groups. In the folate-deficient mice, the blastocyst could implant in the mesangial contralateral visibly. Stroma cell decidulization occurred around the blastocyst continuously and formed the primary decidual zone and secondary decidual zone gradually. The development of the blastocyst was normal as well. However, the significant abnormalities were observed in the vascular density and the enlargement and elongation of vascular sinus folding in folate-deficient pregnant mice, as evidenced with CD34 staining from E6 to E8 (Figure 2). Normally, variable-sized vascular sinus foldings [21] are distributed symmetrically in the central region of the uterus and are enlarged and elongated over time, whereas fine mesh-like blood vessels are arrayed in the anti-mesometrial region, which was similar to our findings (Figure 2). Closer observation of the central region revealed that the sprouting process was most active at E6 (Figure 2A), whereas enlargement and elongation of vascular sinus folding and intussusception of blood vessels [22] were dominant from E7 to E8. Time-series analyses indicated that, compared with E6, the number of large-sized vascular sinus foldings in the central region as well as blood vessel densities in the anti-mesometrial region were markedly increased at E7 and E8 (Figure 2B,C). A significant decrease in vascular density was observed in the folate-deficient group from E6 to E8 as compared with the normal group (Figure 2). The vascular sinus foldings, which predominantly extend into the intermediate zone from the mesometrial to the anti-mesometrial region of the decidua, appeared to be diminished in the folate-deficient group as compared with the normal group, especially at E7 and E8 (Figure 2B,C).

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