The role of ACE2, angiotensin-(1–7) and Mas1 receptor axis in glucocorticoid-induced intrauterine growth restriction
Abstract Background Plasma and urine levels of the potent vasodilator Ang-(1–7) are elevated in mid and late pregnancy and are correlated with elevated placental angiogenesis, fetal blood flow, and rapid fetal growth. We hypothesized that Ang-(1–7), its receptor (Mas1) and the enzymes involved in An...
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| Format: | Article |
| Language: | English |
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BMC
2017-12-01
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| Series: | Reproductive Biology and Endocrinology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12958-017-0316-8 |
| _version_ | 1811302948246913024 |
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| author | Elham Ghadhanfar Aseel Alsalem Shaimaa Al-Kandari Jumana Naser Fawzi Babiker Maie Al-Bader |
| author_facet | Elham Ghadhanfar Aseel Alsalem Shaimaa Al-Kandari Jumana Naser Fawzi Babiker Maie Al-Bader |
| author_sort | Elham Ghadhanfar |
| collection | DOAJ |
| description | Abstract Background Plasma and urine levels of the potent vasodilator Ang-(1–7) are elevated in mid and late pregnancy and are correlated with elevated placental angiogenesis, fetal blood flow, and rapid fetal growth. We hypothesized that Ang-(1–7), its receptor (Mas1) and the enzymes involved in Ang-(1–7) production (ACE2 and Membrane metallo-endopeptidase; MME) are down regulated in response to glucocorticoid administration contributing to IUGR. Methods Pregnant female Sprague–Dawley rats were injected with dexamethasone (DEX; 0.4 mg/kg/day) starting from 14 day gestation (dg) till sacrifice at 19 or 21 dg while control groups were injected with saline (n = 6/group). The gene and protein expression of ACE2, MME, Ang-(1–7) and Mas1 receptor in the placental labyrinth (LZ) and basal zones (BZ) were studied. Results DEX administration caused a reduction in LZ weight at 19 and 21 dg (p < 0.001). IUGR, as shown by decreased fetal weights, was evident in DEX treated rats at 21 dg (p < 0.01). ACE2 gene expression was elevated in the LZ of control placentas at 21 dg (p < 0.01) compared to 19 dg and DEX prevented this rise at both gene (p < 0.01) and protein levels (p < 0.05). In addition, Ang-(1–7) protein expression in LZ was significantly reduced in DEX treated rats at 21 dg (p < 0.05). On the other hand, Mas1 and MME were upregulated in LZ at 21 dg in both groups (p < 0.05 and p < 0.001, respectively). Conclusion The results of this study indicate that a reduced expression of ACE2 and Ang-(1–7) in the placenta by DEX treatment may be responsible for IUGR and consequent disease programming later in life. |
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| format | Article |
| id | doaj.art-d30a4f5fc3db41769bdb816a383516b9 |
| institution | Directory Open Access Journal |
| issn | 1477-7827 |
| language | English |
| last_indexed | 2024-04-13T07:38:25Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Reproductive Biology and Endocrinology |
| spelling | doaj.art-d30a4f5fc3db41769bdb816a383516b92022-12-22T02:56:03ZengBMCReproductive Biology and Endocrinology1477-78272017-12-011511910.1186/s12958-017-0316-8The role of ACE2, angiotensin-(1–7) and Mas1 receptor axis in glucocorticoid-induced intrauterine growth restrictionElham Ghadhanfar0Aseel Alsalem1Shaimaa Al-Kandari2Jumana Naser3Fawzi Babiker4Maie Al-Bader5Department of Physiology, Faculty of Medicine, Kuwait UniversityFaculty of Medicine, Kuwait UniversityFaculty of Medicine, Kuwait UniversityFaculty of Medicine, Kuwait UniversityDepartment of Physiology, Faculty of Medicine, Kuwait UniversityDepartment of Physiology, Faculty of Medicine, Kuwait UniversityAbstract Background Plasma and urine levels of the potent vasodilator Ang-(1–7) are elevated in mid and late pregnancy and are correlated with elevated placental angiogenesis, fetal blood flow, and rapid fetal growth. We hypothesized that Ang-(1–7), its receptor (Mas1) and the enzymes involved in Ang-(1–7) production (ACE2 and Membrane metallo-endopeptidase; MME) are down regulated in response to glucocorticoid administration contributing to IUGR. Methods Pregnant female Sprague–Dawley rats were injected with dexamethasone (DEX; 0.4 mg/kg/day) starting from 14 day gestation (dg) till sacrifice at 19 or 21 dg while control groups were injected with saline (n = 6/group). The gene and protein expression of ACE2, MME, Ang-(1–7) and Mas1 receptor in the placental labyrinth (LZ) and basal zones (BZ) were studied. Results DEX administration caused a reduction in LZ weight at 19 and 21 dg (p < 0.001). IUGR, as shown by decreased fetal weights, was evident in DEX treated rats at 21 dg (p < 0.01). ACE2 gene expression was elevated in the LZ of control placentas at 21 dg (p < 0.01) compared to 19 dg and DEX prevented this rise at both gene (p < 0.01) and protein levels (p < 0.05). In addition, Ang-(1–7) protein expression in LZ was significantly reduced in DEX treated rats at 21 dg (p < 0.05). On the other hand, Mas1 and MME were upregulated in LZ at 21 dg in both groups (p < 0.05 and p < 0.001, respectively). Conclusion The results of this study indicate that a reduced expression of ACE2 and Ang-(1–7) in the placenta by DEX treatment may be responsible for IUGR and consequent disease programming later in life.http://link.springer.com/article/10.1186/s12958-017-0316-8DexamethasoneIUGRAng-(1–7)ACE2MMEMas1 receptor |
| spellingShingle | Elham Ghadhanfar Aseel Alsalem Shaimaa Al-Kandari Jumana Naser Fawzi Babiker Maie Al-Bader The role of ACE2, angiotensin-(1–7) and Mas1 receptor axis in glucocorticoid-induced intrauterine growth restriction Reproductive Biology and Endocrinology Dexamethasone IUGR Ang-(1–7) ACE2 MME Mas1 receptor |
| title | The role of ACE2, angiotensin-(1–7) and Mas1 receptor axis in glucocorticoid-induced intrauterine growth restriction |
| title_full | The role of ACE2, angiotensin-(1–7) and Mas1 receptor axis in glucocorticoid-induced intrauterine growth restriction |
| title_fullStr | The role of ACE2, angiotensin-(1–7) and Mas1 receptor axis in glucocorticoid-induced intrauterine growth restriction |
| title_full_unstemmed | The role of ACE2, angiotensin-(1–7) and Mas1 receptor axis in glucocorticoid-induced intrauterine growth restriction |
| title_short | The role of ACE2, angiotensin-(1–7) and Mas1 receptor axis in glucocorticoid-induced intrauterine growth restriction |
| title_sort | role of ace2 angiotensin 1 7 and mas1 receptor axis in glucocorticoid induced intrauterine growth restriction |
| topic | Dexamethasone IUGR Ang-(1–7) ACE2 MME Mas1 receptor |
| url | http://link.springer.com/article/10.1186/s12958-017-0316-8 |
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