Акушерство и Гинекология Санкт-Петербурга. 2019; : 19-24
Современные представления о патогенезе гипоксии плода и роли в нем гипоксия-индуцируемого фактора (HIF)
Аннотация
В обзоре представлены данные литературы о гипоксии плода и роли в ней гипоксия-индуцируемого фактора (HIF). Особое внимание сконцентрировано на рассмотрении физиологических характеристик HIF в условиях нормоксии и гипоксии.
Список литературы
1. Кирова Ю.И. Регуляторная роль сукцинатзависимых сигнальных систем (HIF-1α и GPR91) при адаптации к гипоксии (экспериментальное исследование): Дисс. …д-р биол. наук. М.; 2016: 279.
2. Alam H., Weck J., Maizels E. et al. Role of the phosphatidylinositol-3-kinase and extracellular regulated kinase pathways in the induction of hypoxia-inducible factor (HIF)-1 activity and the HIF-1 target vascular endothelial growth factor in ovarian granulosa cells in response to folliclestimulating hormone. J.Endocrinology. 2009; 150 (2): 915-928.
3. Berra E., Roux D., Richard D.E., Pouyssegur J. Hypoxia inducible factor-1a (HIF1a) escapes O2-driven proteasomal degradation irrespective of its subcellular localization: nucleus or cytoplasm. EMBO Rep. 2001; 2 (7): 615-620.
4. Fandrey J., Gorr T.A., Gassmann M. Regulating cellular oxygen sensing by hydroxylation. J. Cardiovasc. Res. 2006; 71 (4): 642-651.
5. Wang G.L., Semenza G.L. General involvement of hypoxia-inducible factor 1 in transcriptional response hypoxia. Proc. Natl. Acad. Sci. U.S.A. 1993; 90 (9): 4304-4308.
6. Wang G.L., Semenza G.L. Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction. Blood. 1993; 82: 3610-3615.
7. Wang G.L., Jiang B.H., Semenza G.L. etal. Effect of protein kinase and phosphatase inhibitors on expression of hypoxiainducible factor 1. Biochem. Biophys. Res. Commun. 1995; 216: 669-675.
8. Wang G.L., Semenza G.L. Purification and characterization of hypoxia-inducible factor 1. J. Biol. Chem. 1995; 270 (3): 1230-1237.
9. Antonsson С., Arulampalam V., Whitelaw M.L. et al. Constitutive function of the basic helix-loop-helix/PAS factor Arnt. Regulation of target promoters via the E box motif. C J Biol Chem. 1995 Jun 9; 270 (23): 13968-72.
10. Berra E., Benizri E., Ginouves A. et al. HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1 in normoxia. The EMBO Journal. 2003; 22 (16): 4082-4090.
11. Bruik R.K. Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc. Natl. Acad. Sci. 2000; 97: 9082-9087.
12. Carmeliet P.I., Dor Y., M.Herbert J. et al. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature. 1998; 30: 485-90.
13. Carrero P.I., Okamoto K., Coumailleau P. et al. Redox-regulated recruitment of the transcriptional coactivators CREB-binding protein and SRC-1 to hypoxia-inducible factor 1alpha. Mol Cell Biol. 2000; 20 (1): 402-15.
14. Catrina S.B., Okamoto K., Pereira T. et al. Hyperglycemia regulates hypoxia-inducible factor-1alpha protein stability and function. Diabetes. 2004; 53 (12): 3226-32.
15. Xia Y., Choi H.K., Lee K. Recent advances in hypoxia-inducible factor (HIF)-1 inhibitors. Eur J Med Chem. 2012; 49: 24-40.
16. Correia S.C., Moreira P.I. Hypoxia-inducible factor 1: a new hope to counteract neurodegeneration? J. Neurochem. 2010; 112 (1): 1-12.
17. Dimasuay K.G., Boeuf P., Powell T.L. etal. Placental responses to changes in the maternal environment determine fetal Growth. Front. Physiol. 2016; 7: 12.
18. Dubinsky V., Poehlmann T., Suman P. et al. Role of regulatory and angiogenic cytokines in invasion of trophoblastic cells. J. Reproductive Immunol. 2010; 63: 193-199.
19. D’Angelo G., Duplan E., Boyer N. et al. Hypoxia up-regulates prolyl hydroxylase activity: a feedback mechanism that limits HIF-1 responses during reoxygenation. J. Biol Chem. 2003; 278 (40): 38183-38187.
20. Faa A., Faa G., Papalois A. et al. Effects of Erythropoietin Administration on Cardiomyocytes in Landrace. Large White Pigs after Ventricular Fibrillation. J. Clin. Cardiol. 2016: 1-6.
21. Stockmann C., Fandrey J. Hypoxia-induced erythropoietin production: a paradigm for oxygen-regulated gene expression. Clin. Exp Pharmacol Physiol. 2006; 33 (10): 968-979.
22. Gradin K., Takasaki C., Fujii-Kuriyama Y. et al. The transcriptional activation function of the HIF-like factor requires phosphorylation at a conserved threonine. J. Biol. Chem. 2002; 277: 23508-23514.
23. Helton R., Cui J., Scheel J.R. et al. Brain-Specific Knock-Outof Hypoxia-Inducible Factor-1α Reduces Rather Than Increases Hypoxic-Ischemic Damage. The j. of Neuroscience. 2005; 25 (16): 4099-4107.
24. Hewitson K.S., McNeill L.A., Riordan M.V. et al. Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. J Biol Chem. 2002; 277 (29): 26351-26355.
25. Huang L.E, Gu J., Schau M. et al. Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc. Natl Acad Sci USA. 1998; 95 (14): 7987-8992.
26. Hudson C.C., Liu M., Chiang G.G. et al. Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. J.Mol. Cell. Biol. 2002; 22 (20): 7004-7014.
27. Huppertz I., Attig J., D’Ambrogio A. et al. iCLIP: protein-RNA interactions at nucleotide resolution. J.Methods. 2014; 65 (3): 274-287.
28. Ietta F., Wu Y., Winter J., Xu J., Wang J., Post M. et al. Dynamic HIF1a regulation during human placental development. Biology of Reproduction. 2006; 75: 112-121.
29. Ivan M., Kondo K., Yang H. et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. J.Science. 2001; 292: 464-468.
30. Kaelin W.G. Jr., Ratcliffe P.J. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. J.Mol. Cell. 2008; 30: 393-402.
31. Katschinski D.M., Le L., Schindler S.G. et al. Interaction of the PAS B domain with HSP90 accelerates hypoxia-inducible factor-1 alpha; stabilization. J.Cell Physiol Biochem. 2004; 14 (4): 351-360.
32. Kim J.W., Tchernyshyov I., Semenza G.L. et al. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. J.Cell Metab. 2006; 3: 177-185.
33. Lando D., Peet D.J., Whelan D.A. et al. Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. J.Science. 2002; 295: 858-861.
34. Levine B., Klionsky D.J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. J. Dev Cell. 2004; 6: 463-477.
35. Lonergan K.M., Iliopoulos O., Ohh M. etal. Regulation of hypoxia-inducible mRNAs by the von Hippel-Lindau tumor suppressor protein requires binding to complexes containing elongins B/C and Cul2. J.Mol Cell Biol. 1998; 18: 732-741.
36. Laughner E., Taghavi P., Chiles K. et al. HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. J. Mol Cell Biol. 2001; 21: 3995-4004.
37. Mahon P.C., Hirota K., Semenza G.L. FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. J.Genes Dev. 2001; 15: 2675-2686.
38. Maiuri M.C., Zalckvar E., Kimchi A. et al. Self-eating and self-killing: crosstalk between autophagy and apoptosis. J.Nat.Rev. Mol. Cell. Biol. 2007; 8: 741-752.
39. Masson N., Willam C., Maxwell P.H. et al. Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation. J.EMBO. 2001; 20: 5197-5206.
40. Mellor H.R., Harris A.L. The role of the hypoxia-inducible BH3-only proteins BNIP3 and BNIP3L in cancer. J. Cancer Metastasis Rev. 2007; 26: 553-566.
41. Metzen E., Berchner-Pfannschmidt U., Stengel P. et al. Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing. J. Cell. Sci. 2003; 116: 1319-1326.
42. Ojeda S.R., Lomniczi A., Sandau U.S. Glial-gonadotrophin hormone (GnRH) neurone interactions in the median eminence and the control of GnRH secretion. J. Neuroendocrinol. 2008; 20: 732-742.
43. Onogi A., Naruse K., Sado T. et al. Hypoxia inhibits invasion of extravillous trophoblast cells through reduction of matrix metalloproteinase (MMP)-2 activation in the early first trimester of human pregnancy. Placenta. 2011; 32: 665-670.
44. Papandreou I., Cairns R.A., Fontana L. et al. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. J.Cell. Metab. 2006; 3: 187-197.
45. Piret J.P., Mottet D., Raes M. et al. CoCl2, a chemical inducer of hypoxia-inducible factor-1, and hypoxia reduce apoptotic cell death in hepatoma cell line HepG2. J.Ann.Acad. Sci. 2002; 973: 443-447.
46. Schlotz W., Phillips D.W. Fetal origins of mental health: Evidence and mechanisms. J. Brain Behav. Immun. 23: 905-916
47. Newby J.M. Systematic review and meta-analysis of transdiagnostic psychological treatments for anxiety and depressive disorders in adulthood. J.Clinical Psychology Review. 2015; 40: 91-110.
48. Huppertz C. The Dopaminergic Reward System and Leisure Time Exercise Behavior: A Candidate Allele Study. J. BioMed Research International. 2014; 4: 9-16.
49. Richardson B.S., Bocking A.D. Metabolic and circulatory adaptations to chronic hypoxia in the fetus. J.Comp Biochem Physiol A Mol Integr Physiol. 1998; 119: 717-23.
50. Semenza G.L., Wang G.L. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. J. Mol. Cell. Biol. 1992; 12: 5447-5454.
51. Semenza G.L. Regulation of cancer cell metabolism by hypoxia-inducible factor 1. J.Semin Cancer Biol. 2009; 19: 12-6, 320.
52. Semenza G.L. Targeting HIF-1 for cancer therapy. J.Nat.Rev.Cancer. 2003; 3 (10): 721-732.
53. Semenza G.L. Regulation of oxygen homeostasis by hypoxia-inducible factor 1. J.Physiology. 2009; 24 (97): 96-106.
54. Rajakumar A., Conrad K.P. Expression, ontogeny, and regulation of hypoxiainducible transcription factors in the human placenta. J.Biol. Reprod. 2000; 63: 559-569.
55. Cowden Dahl K.D., Fryer B.H., Mack F.A. et al. Hypoxia-inducible factors 1alpha and 2alpha regulate trophoblast differentiation. J.Mol. Cell. Biol. 2005; 25: 10479-10491.
56. Tissot van Patot M.C., Murray A.J., Beckey V. et al. Human placental metabolic adaptation to chronic hypoxia, high altitude: hypoxic preconditioning. J. Physiol. Regul. Integr. Comp. Physiol. 2010; 298: 166-172.
Obstetrics and Gynaecology of Saint-Petersburg. 2019; : 19-24
Modern ideas about the pathogenesis of fetal hypoxia and the role of hypoxia-inducible factor (HIF) in it
Abstract
References
1. Kirova Yu.I. Regulyatornaya rol' suktsinatzavisimykh signal'nykh sistem (HIF-1α i GPR91) pri adaptatsii k gipoksii (eksperimental'noe issledovanie): Diss. …d-r biol. nauk. M.; 2016: 279.
2. Alam H., Weck J., Maizels E. et al. Role of the phosphatidylinositol-3-kinase and extracellular regulated kinase pathways in the induction of hypoxia-inducible factor (HIF)-1 activity and the HIF-1 target vascular endothelial growth factor in ovarian granulosa cells in response to folliclestimulating hormone. J.Endocrinology. 2009; 150 (2): 915-928.
3. Berra E., Roux D., Richard D.E., Pouyssegur J. Hypoxia inducible factor-1a (HIF1a) escapes O2-driven proteasomal degradation irrespective of its subcellular localization: nucleus or cytoplasm. EMBO Rep. 2001; 2 (7): 615-620.
4. Fandrey J., Gorr T.A., Gassmann M. Regulating cellular oxygen sensing by hydroxylation. J. Cardiovasc. Res. 2006; 71 (4): 642-651.
5. Wang G.L., Semenza G.L. General involvement of hypoxia-inducible factor 1 in transcriptional response hypoxia. Proc. Natl. Acad. Sci. U.S.A. 1993; 90 (9): 4304-4308.
6. Wang G.L., Semenza G.L. Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction. Blood. 1993; 82: 3610-3615.
7. Wang G.L., Jiang B.H., Semenza G.L. etal. Effect of protein kinase and phosphatase inhibitors on expression of hypoxiainducible factor 1. Biochem. Biophys. Res. Commun. 1995; 216: 669-675.
8. Wang G.L., Semenza G.L. Purification and characterization of hypoxia-inducible factor 1. J. Biol. Chem. 1995; 270 (3): 1230-1237.
9. Antonsson S., Arulampalam V., Whitelaw M.L. et al. Constitutive function of the basic helix-loop-helix/PAS factor Arnt. Regulation of target promoters via the E box motif. C J Biol Chem. 1995 Jun 9; 270 (23): 13968-72.
10. Berra E., Benizri E., Ginouves A. et al. HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1 in normoxia. The EMBO Journal. 2003; 22 (16): 4082-4090.
11. Bruik R.K. Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc. Natl. Acad. Sci. 2000; 97: 9082-9087.
12. Carmeliet P.I., Dor Y., M.Herbert J. et al. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature. 1998; 30: 485-90.
13. Carrero P.I., Okamoto K., Coumailleau P. et al. Redox-regulated recruitment of the transcriptional coactivators CREB-binding protein and SRC-1 to hypoxia-inducible factor 1alpha. Mol Cell Biol. 2000; 20 (1): 402-15.
14. Catrina S.B., Okamoto K., Pereira T. et al. Hyperglycemia regulates hypoxia-inducible factor-1alpha protein stability and function. Diabetes. 2004; 53 (12): 3226-32.
15. Xia Y., Choi H.K., Lee K. Recent advances in hypoxia-inducible factor (HIF)-1 inhibitors. Eur J Med Chem. 2012; 49: 24-40.
16. Correia S.C., Moreira P.I. Hypoxia-inducible factor 1: a new hope to counteract neurodegeneration? J. Neurochem. 2010; 112 (1): 1-12.
17. Dimasuay K.G., Boeuf P., Powell T.L. etal. Placental responses to changes in the maternal environment determine fetal Growth. Front. Physiol. 2016; 7: 12.
18. Dubinsky V., Poehlmann T., Suman P. et al. Role of regulatory and angiogenic cytokines in invasion of trophoblastic cells. J. Reproductive Immunol. 2010; 63: 193-199.
19. D’Angelo G., Duplan E., Boyer N. et al. Hypoxia up-regulates prolyl hydroxylase activity: a feedback mechanism that limits HIF-1 responses during reoxygenation. J. Biol Chem. 2003; 278 (40): 38183-38187.
20. Faa A., Faa G., Papalois A. et al. Effects of Erythropoietin Administration on Cardiomyocytes in Landrace. Large White Pigs after Ventricular Fibrillation. J. Clin. Cardiol. 2016: 1-6.
21. Stockmann C., Fandrey J. Hypoxia-induced erythropoietin production: a paradigm for oxygen-regulated gene expression. Clin. Exp Pharmacol Physiol. 2006; 33 (10): 968-979.
22. Gradin K., Takasaki C., Fujii-Kuriyama Y. et al. The transcriptional activation function of the HIF-like factor requires phosphorylation at a conserved threonine. J. Biol. Chem. 2002; 277: 23508-23514.
23. Helton R., Cui J., Scheel J.R. et al. Brain-Specific Knock-Outof Hypoxia-Inducible Factor-1α Reduces Rather Than Increases Hypoxic-Ischemic Damage. The j. of Neuroscience. 2005; 25 (16): 4099-4107.
24. Hewitson K.S., McNeill L.A., Riordan M.V. et al. Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. J Biol Chem. 2002; 277 (29): 26351-26355.
25. Huang L.E, Gu J., Schau M. et al. Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc. Natl Acad Sci USA. 1998; 95 (14): 7987-8992.
26. Hudson C.C., Liu M., Chiang G.G. et al. Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. J.Mol. Cell. Biol. 2002; 22 (20): 7004-7014.
27. Huppertz I., Attig J., D’Ambrogio A. et al. iCLIP: protein-RNA interactions at nucleotide resolution. J.Methods. 2014; 65 (3): 274-287.
28. Ietta F., Wu Y., Winter J., Xu J., Wang J., Post M. et al. Dynamic HIF1a regulation during human placental development. Biology of Reproduction. 2006; 75: 112-121.
29. Ivan M., Kondo K., Yang H. et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. J.Science. 2001; 292: 464-468.
30. Kaelin W.G. Jr., Ratcliffe P.J. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. J.Mol. Cell. 2008; 30: 393-402.
31. Katschinski D.M., Le L., Schindler S.G. et al. Interaction of the PAS B domain with HSP90 accelerates hypoxia-inducible factor-1 alpha; stabilization. J.Cell Physiol Biochem. 2004; 14 (4): 351-360.
32. Kim J.W., Tchernyshyov I., Semenza G.L. et al. HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. J.Cell Metab. 2006; 3: 177-185.
33. Lando D., Peet D.J., Whelan D.A. et al. Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. J.Science. 2002; 295: 858-861.
34. Levine B., Klionsky D.J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. J. Dev Cell. 2004; 6: 463-477.
35. Lonergan K.M., Iliopoulos O., Ohh M. etal. Regulation of hypoxia-inducible mRNAs by the von Hippel-Lindau tumor suppressor protein requires binding to complexes containing elongins B/C and Cul2. J.Mol Cell Biol. 1998; 18: 732-741.
36. Laughner E., Taghavi P., Chiles K. et al. HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression. J. Mol Cell Biol. 2001; 21: 3995-4004.
37. Mahon P.C., Hirota K., Semenza G.L. FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. J.Genes Dev. 2001; 15: 2675-2686.
38. Maiuri M.C., Zalckvar E., Kimchi A. et al. Self-eating and self-killing: crosstalk between autophagy and apoptosis. J.Nat.Rev. Mol. Cell. Biol. 2007; 8: 741-752.
39. Masson N., Willam C., Maxwell P.H. et al. Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation. J.EMBO. 2001; 20: 5197-5206.
40. Mellor H.R., Harris A.L. The role of the hypoxia-inducible BH3-only proteins BNIP3 and BNIP3L in cancer. J. Cancer Metastasis Rev. 2007; 26: 553-566.
41. Metzen E., Berchner-Pfannschmidt U., Stengel P. et al. Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing. J. Cell. Sci. 2003; 116: 1319-1326.
42. Ojeda S.R., Lomniczi A., Sandau U.S. Glial-gonadotrophin hormone (GnRH) neurone interactions in the median eminence and the control of GnRH secretion. J. Neuroendocrinol. 2008; 20: 732-742.
43. Onogi A., Naruse K., Sado T. et al. Hypoxia inhibits invasion of extravillous trophoblast cells through reduction of matrix metalloproteinase (MMP)-2 activation in the early first trimester of human pregnancy. Placenta. 2011; 32: 665-670.
44. Papandreou I., Cairns R.A., Fontana L. et al. HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. J.Cell. Metab. 2006; 3: 187-197.
45. Piret J.P., Mottet D., Raes M. et al. CoCl2, a chemical inducer of hypoxia-inducible factor-1, and hypoxia reduce apoptotic cell death in hepatoma cell line HepG2. J.Ann.Acad. Sci. 2002; 973: 443-447.
46. Schlotz W., Phillips D.W. Fetal origins of mental health: Evidence and mechanisms. J. Brain Behav. Immun. 23: 905-916
47. Newby J.M. Systematic review and meta-analysis of transdiagnostic psychological treatments for anxiety and depressive disorders in adulthood. J.Clinical Psychology Review. 2015; 40: 91-110.
48. Huppertz C. The Dopaminergic Reward System and Leisure Time Exercise Behavior: A Candidate Allele Study. J. BioMed Research International. 2014; 4: 9-16.
49. Richardson B.S., Bocking A.D. Metabolic and circulatory adaptations to chronic hypoxia in the fetus. J.Comp Biochem Physiol A Mol Integr Physiol. 1998; 119: 717-23.
50. Semenza G.L., Wang G.L. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. J. Mol. Cell. Biol. 1992; 12: 5447-5454.
51. Semenza G.L. Regulation of cancer cell metabolism by hypoxia-inducible factor 1. J.Semin Cancer Biol. 2009; 19: 12-6, 320.
52. Semenza G.L. Targeting HIF-1 for cancer therapy. J.Nat.Rev.Cancer. 2003; 3 (10): 721-732.
53. Semenza G.L. Regulation of oxygen homeostasis by hypoxia-inducible factor 1. J.Physiology. 2009; 24 (97): 96-106.
54. Rajakumar A., Conrad K.P. Expression, ontogeny, and regulation of hypoxiainducible transcription factors in the human placenta. J.Biol. Reprod. 2000; 63: 559-569.
55. Cowden Dahl K.D., Fryer B.H., Mack F.A. et al. Hypoxia-inducible factors 1alpha and 2alpha regulate trophoblast differentiation. J.Mol. Cell. Biol. 2005; 25: 10479-10491.
56. Tissot van Patot M.C., Murray A.J., Beckey V. et al. Human placental metabolic adaptation to chronic hypoxia, high altitude: hypoxic preconditioning. J. Physiol. Regul. Integr. Comp. Physiol. 2010; 298: 166-172.
