Placenta: an organ with high energy requirements

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Abstract

Placenta is a unique organ, without which the very phenomenon of human pregnancy is impossible. Semiallogeneous nature, localization of the placenta, complex and heterogeneous cellular composition determines its complex and multifaceted role in the course of physiological pregnancy, indicates the importance of studying this organ in a number of reproductive pathologies. The purpose of this review was to analyze the literature sources illustrating the importance of energydependent processes in placental metabolism and to determine the molecular basis of placental energy conversion. Publications of foreign and Russian authors from PubMed database and scientific electronic library eLIBRARY.ru were used when writing the review. The review highlights the main functions of the placenta: transport and synthetic functions in terms of their place in the structure of energy expenditure of the organ. The systems by which the transport of ions and gases from maternal blood through the placental barrier is performed, are considered. The role of the placenta in the synthesis of steroid hormones and glucocorticoids is detailed. The main bioenergetic systems are also considered: placental glucose metabolism, the functional activity of mitochondria and the creatine kinase system of the placenta. These data allow us to put the placenta on a par with other organs with high energy requirements (brain, transverse striated skeletal muscles, heart, kidneys, liver), which are most susceptible to metabolic disorders. Maintaining a balance between expenditure and synthesis of macroergic compounds in the placenta is critical for an adequate course of physiological pregnancy, and imbalances can lead to such pathologies as fetal retardation syndrome or preeclampsia. Further study of placental energy supply systems seems important for understanding the mechanisms of intrauterine development disorders and developing their pathogenetic treatment.

About the authors

Maia A. Shestakova

National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov

Email: vpa2002@mail.ru
ORCID iD: 0000-0002-6154-9481
Moscow, Russian Federation

Polina A. Vishnyakova

National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov

Author for correspondence.
Email: vpa2002@mail.ru
ORCID iD: 0000-0001-8650-8240
Moscow, Russian Federation

Timur Kh. Fatkhudinov

Avtsyn Research Institute of Human Morphology of Federal state budgetary scientific institution “Petrovsky National Research Centre of Surgery”

Email: vpa2002@mail.ru
ORCID iD: 0000-0002-6498-5764
Moscow, Russian Federation

References

  1. Enders AC, Blankenship TN, Fazleabas AT, Jones CJP. Structure of anchoring villi and the trophoblastic shell in the human, baboon and macaque placenta. Placenta. 2001;22(4):284-303. doi: 10.1053/plac.2001.0626
  2. Bloise E, Ortiga-Carvalho TM, Reis FM, Lye SJ, Gibb W, Matthews S. ATP-binding cassette transporters in reproduction: a new frontier. Hum Reprod Update. 2016;22(2):164-181. doi:10.1093/ humupd/dmv049
  3. Sibley CP, Birdsey TJ, Brownbill P, Clarson LH, Doughty I, Glazier JD. Mechanisms of maternofetal exchange across the human placenta. Biochem Soc Trans. 1998;26(2):86-91.
  4. Walker N, Filis P, Soffientini U, Bellingham M, O’Shaughnessy PJ, Fowler PA. Placental transporter localization and expression in the Human: the importance of species, sex, and gestational age differences. Biol Reprod. 2017;96(4):733-742. doi:10.1093/ biolre/iox012
  5. Johansson M, Jansson T, Powell TL. Na(+)-K(+)ATPase is distributed to microvillous and basal membrane of the syncytiotrophoblast in human placenta. Am J Physiol Regul Integr Comp Physiol. 2000;279(1):287-294. doi: 10.1152/ajpregu.2000.279.1.R 287
  6. Stulc J, Stulcová B, Smíd M, Sach I. Parallel mechanisms of Ca++ transfer across the perfused human placental cotyledon. Am J Obstet Gynecol. 1994;170(1):162-167. doi: 10.1016/s0002- 9378(94)70403-1
  7. Haché S, Takser L, LeBellego F, Weiler H, Leduc L, Forest JC. Alteration of calcium homeostasis in primary preeclamptic syncytiotrophoblasts: effect on calcium exchange in placenta. J Cell Mol Med. 2011;15(3):654-667. doi: 10.1111/j.1582-4934.2010.01039.x
  8. Fowden AL, Forhead AJ, Coan PM, Burton GJ. The placenta and intrauterine programming. J Neuroendocrinol. 2008;20(4):439- 450. doi: 10.1111/j.1365-2826.2008.01663.x
  9. Costa MA. The endocrine function of human placenta: an overview. Reprod Biomed Online. 2016;32(1):14-43. doi:10.1016/j. rbmo.2015.10.005
  10. Lowry P, Woods R. The placenta controls the physiology of pregnancy by increasing the half-life in blood and receptor activity of its secreted peptide hormones. J Mol Endocrinol. 2018;60(1):23-30. doi: 10.1530/jme-17-0275
  11. Kawakami T, Yoshimi M, Kadota Y, Inoue M, Sato M, Suzuki S. Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight. Toxicol Appl Pharmacol. 2014;275(2):134-144. doi: 10.1016/j.taap.2013.12.008
  12. Gaignard P, Liere P, Thérond P, Schumacher M, Slama A, Guennoun R. Role of sex hormones on brain mitochondrial function, with special reference to aging and neurodegenerative diseases. Frontiers in aging neuroscience. 2017;9:406. doi: 10.3389/ fnagi.2017.00406
  13. Tuckey RC, Kostadinovic Z, Cameron KJ. Cytochrome P-450scc activity and substrate supply in human placental trophoblasts. Mol Cell Endocrinol. 1994;105(2):123-9.
  14. Klimek J, Bogusławski W, Zelewski L. The relationship between energy generation and cholesterol side-chain cleavage reaction in the mitochondria from human term placenta. Biochim Biophys Acta. 1979;587(3):362-372. doi: 10.1016/0304-4165(79)90440-9
  15. Stefulj J, Panzenboeck U, Becker T, Hirschmugl B, Schweinzer C, Lang I. Human endothelial cells of the placental barrier efficiently deliver cholesterol to the fetal circulation via ABCA1 and ABCG1. Circ Res. 2009;104(5):600-608. doi:10.1161/ circresaha.108.185066
  16. Sanderson JT. Placental and fetal steroidogenesis. Methods Mol Biol. 2009;550:127-136. doi: 10.1007/978-1-60327-009-0_
  17. Bukovsky A, Cekanova M, Caudle MR, Wimalasena J, Foster JS, Henley DC, Elder RF. Expression and localization of estrogen receptor-alpha protein in normal and abnormal term placentae and stimulation of trophoblast differentiation by estradiol. Reprod Biol Endocrinol. 2003;1:13. doi: 10.1186/1477-7827-1-13
  18. Ozer A, Tolun F, Aslan F, Hatirnaz S, Alkan F. The role of G protein-associated estrogen receptor (GPER) 1, corin, raftlin, and estrogen in etiopathogenesis of intrauterine growth retardation. The Journal of Maternal-Fetal & Neonatal Medicine. 2021;34(5):755-760. doi: 10.1080/14767058.2019.1615433
  19. Irwin RW, Yao J, Hamilton RT, Cadenas E, Brinton RD, Nilsen J. Progesterone and estrogen regulate oxidative metabolism in brain mitochondria. Endocrinology. 2008;149(6):3167-3175. doi: 10.1210/en.2007-1227
  20. Wang J, Green PS, Simpkins JW. Estradiol protects against ATP depletion, mitochondrial membrane potential decline and the generation of reactive oxygen species induced by 3-nitroproprionic acid in SK-N-SH human neuroblastoma cells. J Neurochem. 2001;77(3):804-11.
  21. Klinge CM. Estrogenic control of mitochondrial function and biogenesis. J Cell Biochem. 2008;105(6):1342-1351. doi:10.1002/ jcb.21936
  22. Yager JD, Chen JQ. Mitochondrial estrogen receptors - new insights into specific functions. Trends Endocrinol Metab. 2007;18(3):89-91. doi: 10.1016/j.tem.2007.02.006
  23. Chatuphonprasert W, Jarukamjorn K, Ellinger I. Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta. Front Pharmacol. 2018;9:1027. doi:10.3389/ fphar.2018.01027
  24. Hay WW. Glucose metabolism in the fetal-placental unit. In: Cowett RM, editors. Principles of Perinatal-Neonatal Metabolsm. New York: Springer; 1991. p. 250-275.
  25. Diamant YZ, Mayorek N, Neumann S, Shafrir E. Enzymes of glucose and fatty acid metabolism in early and term human placenta. Am J Obstet Gynecol. 1975;121(1):58-61. doi: 10.1016/0002- 9378(75)90975-8
  26. Bax BE, Bloxam DL. Energy metabolism and glycolysis in human placental trophoblast cells during differentiation. Biochim Biophys Acta. 1997;1319(2-3):283-292. doi: 10.1016/s0005- 2728(96)00169-7
  27. Williams SF, Fik E, Zamudio S, Illsley NP. Global protein synthesis in human trophoblast is resistant to inhibition by hypoxia. Placenta. 2012;33(1):31-38. doi: 10.1016/j.placenta.2011.09.021
  28. Holland O, Dekker Nitert M, Gallo LA, Vejzovic M, Fisher JJ, Perkins AV. Review: Placental mitochondrial function and structure in gestational disorders. Placenta. 2017; 54:2-9. doi:10.1016/j. placenta.2016.12.012
  29. Jones CJ, Harris LK, Whittingham J, Aplin JD, Mayhew TM. A re-appraisal of the morphophenotype and basal lamina coverage of cytotrophoblasts in human term placenta. Placenta. 2008;29(2):215 doi: 10.1016/j.placenta.2007.11.004
  30. Kolahi KS, Valent AM, Thornburg KL. Cytotrophoblast, Not Syncytiotrophoblast, Dominates Glycolysis and Oxidative Phosphorylation in Human Term Placenta. Sci Rep. 2017;7:42941. doi: 10.1038/srep4294
  31. Shekhawat P, Bennett MJ, Sadovsky Y, Nelson DM, Rakheja D, Strauss AW. Human placenta metabolizes fatty acids: implications for fetal fatty acid oxidation disorders and maternal liver diseases. Am J Physiol Endocrinol Metab. 2003;284(6):1098-1105 doi:10.1152/ ajpendo.00481.2002
  32. Oey NA, den Boer ME, Ruiter JP, Wanders RJ, Duran M, Waterham HR. High activity of fatty acid oxidation enzymes in human placenta: implications for fetal-maternal disease. J Inherit Metab Dis. 2003;26(4):385-392.
  33. Thomas MM, Haghiac M, Grozav C, Minium J, CalabuigNavarro V, O’Tierney-Ginn P. Oxidative Stress Impairs Fatty Acid Oxidation and Mitochondrial Function in the Term Placenta. Reprod Sci. 2019;26(7):972-978. doi: 10.1177/1933719118802054
  34. Bartha JL, Visiedo F, Fernández-Deudero A, Bugatto F, Perdomo G. Decreased mitochondrial fatty acid oxidation in placentas from women with preeclampsia. Placenta. 2012;33(2):132-134. doi: 10.1016/j.placenta.2011.11.027
  35. Matsubara S, Takayama T, Iwasaki R, Minakami H, Takizawa T, Sato I. Morphology of the mitochondria and endoplasmic reticula of chorion laeve cytotrophoblasts: their resemblance to villous syncytiotrophoblasts rather than villous cytotrophoblasts. Histochem Cell Biol. 2001;116(1):9-15.
  36. Bucher M, Kadam L, Ahuna K, Myatt L. Differences in Glycolysis and Mitochondrial Respiration between Cytotrophoblast and Syncytiotrophoblast In-Vitro: Evidence for Sexual Dimorphism. International journal of molecular sciences. 2021;22(19). doi: 10.3390/ ijms221910875
  37. Hanukoglu I. Antioxidant protective mechanisms against reactive oxygen species (ROS) generated by mitochondrial P450 systems in steroidogenic cells. Drug metabolism reviews. 2006:38(1- :171-196. doi: 10.1080/03602530600570040
  38. Watson AL, Skepper JN, Jauniaux E, Burton GJ. Susceptibility of human placental syncytiotrophoblastic mitochondria to oxygenmediated damage in relation to gestational age. J Clin Endocrinol Metab. 1998;83(5):1697-1705. doi: 10.1210/jcem.83.5.4830
  39. Holland OJ, Hickey AJR, Alvsaker A, Moran S, Hedges C, Chamley LW. Changes in mitochondrial respiration in the human placenta over gestation. Placenta. 2017; 57:102-112. doi:10.1016/j. placenta.2017.06.011
  40. Vishnyakova PA, Kan NE, Khodzhaeva ZU, Vysokikh MYu. Placental mitochondria in health and in preeclampsia. Obstetrics & Gynecology. 2017;5:5-8. doi: 10.18565/aig.2017.5.5-8. (In Russian).
  41. Perfilova V. Role of placental mitochondria in the etiology and pathogenesis of complicated pregnancy. Obstetrics & Gynecology. 2019;4:5-11. doi: 10.18565/aig.2019.4.5-11. (In Russian).
  42. Thomure MF, Gast MJ, Srivastava N, Payne RM. Regulation of creatine kinase isoenzymes in human placenta during early, mid-, and late gestation. J Soc Gynecol Investig. 1996;3(6):322-327
  43. Payne RM, Friedman DL, Grant JW, Perryman MB, Strauss AW. Creatine kinase isoenzymes are highly regulated during pregnancy in rat uterus and placenta. Am J Physiol. 1993;265(4Pt1):624-635. doi: 10.1152/ajpendo.1993.265.4.E 624
  44. McWhorter ES, Russ JE, Winger QA, Bourma GJ. Androgen and estrogen receptors in placental physiology and dysfunction. Frontiers in Biology. 2018;13(5):315-326. doi: 10.1007/s11515018-1517-z
  45. Kazi AA, Koos RD. Estrogen-induced activation of hypoxiainducible factor-1alpha, vascular endothelial growth factor expression, and edema in the uterus are mediated by the phosphatidylinositol 3-kinase/Akt pathway. Endocrinology. 2007;148(5):2363-2374. doi: 10.1210/en.2006-1394
  46. Steeghs K, Peters W, Brückwilder M, Croes H, Van Alewijk D, Wieringa B. Mouse ubiquitous mitochondrial creatine kinase: gene organization and consequences from inactivation in mouse embryonic stem cells. DNA Cell Biol. 1995;14(6):539-553. doi:10.1089/ dna.1995.14.539
  47. Weisman Y, Golander A, Binderman I, Spirer Z, Kaye AM, Sömjen D. Stimulation of creatine kinase activity by calcium-regulating hormones in explants of human amnion, decidua, and placenta. J Clin Endocrinol Metab. 1986; 63(5):1052-1056. doi: 10.1210/jcem-63- 5-1052
  48. Dickinson H, Ellery S, Della Gatta P, Ghattas L, Baharo S, Davies-Tuck M. A novel energy source for the feto-placental unit- creatine. Placenta. 2014;35(9):68. doi: 10.1016/j.placenta.2014.06.221
  49. Ireland Z, Russell AP, Wallimann T, Walker DW, Snow R. Developmental changes in the expression of creatine synthesizing enzymes and creatine transporter in a precocial rodent, the spiny mouse. BMC Dev Biol. 2009;9:39. doi: 10.1186/1471-213x-9-39
  50. Ellery SJ, Della Gatta PA, Bruce CR, Kowalski GM, Davies-Tuck M, Mockler JC. Creatine biosynthesis and transport by the term human placenta. Placenta. 2017;52:86-93. doi:10.1016/j. placenta.2017.02.020
  51. Sandell LL, Guan XJ, Ingram R, Tilghman SM. Gatm, a creatine synthesis enzyme, is imprinted in mouse placenta. Proc Natl Acad Sci USA. 2003;100(8):4622-4627 doi: 10.1073/pnas.0230424100

Copyright (c) 2022 Shestakova M.A., Vishnyakova P.A., Fatkhudinov T.K.

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