ЗАДЕРЖКА РОСТА ПЛОДА: МОЛЕКУЛЯРНЫЕ АСПЕКТЫ ФОРМИРОВАНИЯ, ПРОГНОЗ НА БУДУЩЕЕ (ОБЗОР ЛИТЕРАТУРЫ)
Реферат
Задержка роста плода (ЗРП) – одна из ведущих причин перинатальной заболеваемости и смертности. Основным механизмом, лежащим в основе задержки роста плода, является хроническая плацентарная дисфункция в виде нарушения адекватного поступления кислорода и питательных веществ к плоду, что и приводит к нарушению его роста и развития. ЗРП ассоциирована с рядом метаболических, сердечно-сосудистых, неврологических нарушений, респираторных заболеваний в раннем младенчестве и в зрелом возрасте, требует длительного диспансерного наблюдения, проведения корригирующей терапии на протяжении всей последующей жизни. В настоящее время большой интерес представляет изучение молекулярных механизмов формирования ЗРП, ее дородовых и послеродовых осложнений. С развитием молекулярной биологии растет список генетических причин ЗРП. В обзоре мы постарались охватить генетические, метаболические и эндокринные факторы, ответственные за развитие ЗРП. Углубленное изучение основных молекулярных механизмов, формирующих ЗРП, позволит расширить спектр профилактических мероприятий, диагностических возможностей ее раннего выявления и своевременной коррекции, что позволит у данной группы пациентов снизить перинатальную заболеваемость, смертность, риск развития краткосрочных и долгосрочных последствий.
Тэги
1. Александрова А.А., Гутникова Л.В., Деревянчук Е.Г. Геномные и постгеномные маркеры развития плаценты и плода. Ростов-на-Дону: ЮФУ, 2011. 48–70.
2. Всемирная организация здравоохранения. Новорожденные: снижение смертности. Информационный бюллетень № 333. Январь 2016 г.
3. Замалеева Р.С., Мальцева Л.И., Черепанова Н.А., Фризина А.В., Лазарева В.К., Юпатов Е.Ю., Коган Я.Э., Фаттахова Ф.А. Состояние проблемы лечения и прогнозирования задержки развития плода // Практ. медицина. 2016. (1). 41–44.
4. Льюин Б., Кассимерис Л., Лингаппа В.П., Плоппер Д. Клетки. М.: БИНОМ, 2011. 951 с.
5. Ремнёва О.В., Буркова Т.В. Социальные и акушерские факторы риска гибели плода в срочных родах // Репродуктивный потенциал России: версии и контрверсии: сб. тез. X Общерос. семинара, Сочи, 9–12 сентября 2017 г. М., 2017. 19–20.
6. Чабанова Н.Б., Матаев С.И., Василькова Т.Н., Трошина И.А. Метаболические нарушения при адипоцитокиновом дисбалансе и гестационные осложнения // Ожирение и метаболизм. 2017. 14. (1). 9–16.
7. Alcаzar M.A., Dinger K., Rother E., Ostreicher I., Vohlen C., Plank C., Dotsch J. Prevention of early postnatal hyperalimentation protects against activation of transforming growth factor-β/bone morphogenetic protein and interleukin-6 signaling in rat lungs after intrauterine growth restriction // J. Nutr. 2014. 144. (12). 1943–1951.
8. Alcazar M.A., Morty R.E., Lendzian L., Vohlen C., Oestreicher I., Plank C., Schneider H., Dötsch J. Inhibition of tgf-β signaling and decreased apoptosis in IUGR-associated lung disease in rats // PLoS One. 2011. 6. (10). e26371.
9. Araujo J.R., Correia-Branco A., Pereira A.C., Pinho M.J., Keating E., Martel F. Oxidative stress decreases uptake of neutral amino acids in a human placental cell line (BeWo cells) // Reprod Toxicol. 2013. 40. 76–81.
10. Arslan M., Yazici G., Erdem A., Erdem M., Ozturk Arslanc E., Himmetoglub O. Endothelin 1 and leptin in the pathophysiology of intrauterine growth restriction // Int. J. Gynaecol. Obstet. 2004. 84. (2). 120–126.
11. Biron-Shental T., Sukenik-Halevy R., Sharon Y., Goldberg-Bittman L., Kidron D., Fejgin M.D., Amiel A. Short telomeres may play a role in placental dysfunction in preeclampsia and intrauterine growth restriction // Am. J. Obstet. Gynecol. 2010. 202. (4). 381. e1–e7.
12. Biron-Shental T., Sukenik-Halevy R., Sharon Y., Laish I., Fejgin M.D., Amiel A. Telomere shortening in intra uterine growth restriction placentas // Early Hum. Dev. 2014. 90. (9). 465–469.
13. Bjarnegard N., Morsing E., Cinthio M., Lanne T., Brodszki J. Cardiovascular function in adulthood following intrauterine growth restriction with abnormal fetal blood flow // Ultrasound Obstet. Gynecol. 2013. 41. (2). 177–184.
14. Borras D., Perales-Puchalt A., Ruiz Sacedon N., Perales A. Angiogenic growth factors in maternal and fetal serum in pregnancies complicated with intrauterine growth restriction // J. Obstet. Gynecol. 2014. 34. 218–220.
15. Borzsonyi B., Demendi C., Nagy Z., Toth K., Csanad M., Pajor A., Rig J.Jr., Joo J.G. Gene expression patterns of insulin-like growth factor 1, insulin-like growth factor 2 and insulin-like growth factor binding protein 3 in human placenta from pregnancies with intrauterine growth restriction // J. Perinat. Med. 2011. 39. (6). 701–707.
16. Borzsonyi B., Demendi C., Pajor A., Rigo J.Jr., Marosi K., Agota A., Nagy Z.B., Joo J.G. Gene expression patterns of the 11b-hydroxysteroid dehydrogenase 2 enzyme in human placenta from intrauterine growth restriction: the role of impaired feto-maternal glucocorticoid metabolism // Eur. J. Obstet. Gynecol. Reprod. Biol. 2012. 161. (1). 12–17.
17. Borzsonyi B., Demendi C., Rigo J., Szentpeteri I., Rab A., Joo J.G. The regulation of apoptosis in intrauterine growth restriction: a study of Bcl-2 and Bax gene expression in human placenta // J. Matern. Fetal. Neonatal. Med. 2013. 26. (4). 347–350.
18. Caniggia I., Winter J.L. Adriana and Luisa Castellucci Award lecture 2001. Hypoxia inducible factor-1: oxygen regulation of trophoblast differentiation in normal and preeclamptic pregnancies a review // Placenta. 2002. 23. 47–57.
19. Casalini P., Iorio M.V., Galmozzi E., Menard S. Role of HER receptors family in development and differentiation // J. Cell Physiol. 2004. 200. (3). 343–350.
20. Cetin I., Mazzocco M.I., Giardini V., Cardellicchio M., Calabrese S., Algeri P., Martinelli A., Todyrenchuk L., Vergani P. PIGF in a clinical setting of pregnancies at risk of preeclampsia and/or intrauterine growth restriction // J. Matern. Fetal Neonatal Med. 2017. 30. (2). 144–149.
21. Chauvin S., Yinon Y., Xu J., Ermini L., Sallais J., Tagliaferro A., Todros T., Post M., Caniggia I. Aberrant TGFβ signalling contributes to dysregulation of sphingolipid metabolism in intrauterine growth restriction // J. Clin. Endocrinol. Metab. 2015. 100. 986–996.
22. Chelbi S.T., Wilson M.L., Veillard A.-C., Ingles S.A., Zhang J., Mondon F., Gascoin-Lachambre G., Doridot L., Mignot T.M., Rebourcet R., Carbonne B., Concordet J.P., Barbaux S., Vaiman D. Genetic and epigenetic mechanisms collaborate to control SERPINA3 expression and its association with placental diseases // Hum. Mol. Genet. 2012. 21. (9). 1968–78.
23. Cowans N.J., Stamatopoulou A., Matwejew E., von Kaisenberg C.S., Spencer K. First-trimester placental growth factor as a marker for hypertensive disorders and SGA // Prenat. Diagn. 2010. 30. 565–570.
24. Diamond F.B. Jr., Eichler D.C. Leptin and the adipocyte endocrine system // Crit. Rev. Clin. Lab. Sci. 2002. 39. (4-5). 499–525.
25. Ferencz A., Orvos H., Hermesz E. Major differences in the levels of redox status and antioxidant defence markers in the erythrocytes of pre- and full-term neonates with intrauterine growth restriction // Reprod. Toxicol. 2015. 53. 10–14.
26. Ferreira J.C., Choufani S., Kingdom J., Weksberg R. Epigenetic programming and fetal growth restrictions // Fetal Matern. Med. Rev. 2010. 21. (3). 204–224.
27. Gascoin-Lachambre G., Buffat C., Rebourcet R., Chelbi S.T., Rigourd V., Mondon F., Mignot T.M., Legras E., Simeoni U., Vaiman D., Barbaux S. Cullins in human intra-uterine growth restriction: expressional and epigenetic alterations // Placenta. 2010. 31. (2). 151–157.
28. Gourvas V., Dalpa E., Konstantinidou A., Vrachnis N., Spandidos D.A., Sifakis S. Angiogenic factors in placentas from pregnancies complicated by fetal growth restriction (review) // Mol. Med. Rep. 2012. 6. 23–27.
29. Harradine K.A., Akhurst R.J. Mutations of TGFß signaling molecules in human disease // Ann. Med. 2006. 38. (6). 403–414.
30. Haşmaşanu M.G., Baizat M., Procopciuc L.M., Blaga L., Valeanu M.A., Drugan T.C., Zaharie G.C., Bolboaca S.D. Serum levels and ApaI polymorphism of insulin-like growth factor 2 on intrauterine growth restriction infants // J. Matern. Fetal Neonatal Med. 2018. 31. (11). 1470–1476.
31. Heshmat S.H. Intrauterine growth restriction – A review article // Anatomy Physiol. Biochem. Int. J. 2017. 1. (5). 555–572.
32. Joo J.G., Rigo J.Jr., Börzsönyi B., Demendi C., Kornya L. Placental gene expression of the placental growth factor (PlGF) in intrauterine growth restriction // J. Matern. Fetal Neonatal Med. 2017. 30. (12). 1471–1475.
33. Ke X., Xing B., Yu B., Yu X., Majnik A., Cohen S., Lane R., Joss-Moore L. IUGR disrupts the PPARγ-Setd8-H4K20me1 and Wnt signaling pathways in the juvenile rat hippocampus // Int. J. Dev. Neurosci. 2014. 38. 59–67.
34. Rao Krishna R., Vishnu Bhat B. Molecular mechanisms of intrauterine growth restriction // J. Matern. Fetal Neonatal Med. 2018. 31. (19). 2634–2640.
35. Lee M.H., Jeon Y.J., Lee S.M., Park M.H., Jung S.C., Kim Y.J. Placental gene expression is related to glucose metabolism and fetal cord blood levels of insulin and insulin-like growth factors in intrauterine growth restriction // Early Hum. Dev. 2010.86. (1). 45–50.
36. Leung J.C., Chan L.Y., Tang S.C., Chu K.M., Lai K.N. Leptin induces TGF-β synthesis through functional leptin receptor expressed by human peritoneal mesothelial cell // Kidney Int. 2006. 69. (11). 2078–2086.
37. Lewis J.B., Mejia C., Jordan C., Monson T.D., Bodine J.S., Dunaway T.M., Egbert K.M., Lewis A.L., Wright T.J., Ogden K.C., Broberg D.S., Hall P.D., Nelson S.M., Hirschi K.M., Reynolds P.R., Arroyo J.A. Inhibition of the receptor for advanced glycation end-products (RAGE) protects from secondhand smoke (SHS) induced intrauterine growth restriction IUGR in mice // Cell Tissue Res. 2017. 370. (3). 513–521.
38. Li S.-W., Ling Y., Jin S., Lin Y.F., Chen Z.J., Hu C.X., Wang M.H., Yao M.Z. Expression of soluble vascular endothelial growth factor receptor-1 and placental growth factor in fetal growth restriction cases and intervention effect of tetramethylpyrazine // Asian Pac. J. Trop. Med. 2014. 7. 663–667.
39. Longo S., Bollani L., Decembrino L., di Comite A., Angelini M., Stronati M. Short-term and long-term sequelae in intrauterine growth retardation (IUGR) // J. Matern. Fetal Neonatal Med. 2013. 26. (3). 222–225.
40. Maisonneuve E., Delvin E., Ouellet A., Morin L., Dube J., Boucoiran I., Moutquin J.M., Fouron J.C., Klam S., Levy E., Leduc L. Oxidative conditions prevail in severe IUGR with vascular disease and Doppler anomalies // J. Matern. Fetal Neonatal Med. 2014. 15. 1–5.
41. Martín-Estal I., de la Garza R.G., Castilla-Cortázar I. Intrauterine growth retardation (IUGR) as a novel condition of insulin-like growth factor-1 (IGF-1) deficiency // Rev. Physiol. Biochem. Pharmacol. 2016. 170. 1–35.
42. Murki S., Sharma D. Intrauterine growth retardation – a review article // J. Neonatal Biol. 2014. 3. 315.
43. Murthi P. Review: placental homeobox genes and their role in regulating human fetal growth // Placenta. 2014. 35. 46–50.
44. Murthi P., Rajaraman G., Brennecke S.P., Kalionis B. The role of placental homeobox genes in human fetal growth restriction // J. Pregnancy. 2011. 2011. 11.
45. Pathirage N.A., Cocquebert M., Sadovsky Y., Abumaree M., Manuelpillai U., Borg A., Keogh R.J., Brennecke S.P., Evain-Brion D., Fournier T., Kalionis B., Murthi P. Homeobox gene transforming growth factor β-induced factor-1 (TGIF-1) is a regulator of villous trophoblast differentiation and its expression is increased in human idiopathic fetal growth restriction // Mol. Hum. Reprod. 2013. 19. (10). 665–675.
46. Peng J., Monsivais D., You R., Zhong H., Pangas S.A., Matzuk M.M. Uterine activin receptor-like kinase 5 is crucial for blastocyst implantation and placental development // Proc. Natl. Acad. Sci. 2015. 112. (36). 5098–5107.
47. Perrone S., Tataranno M.L., Stazzoni G., Buonocore G. Biomarkers of oxidative stress in fetal and neonatal diseases // J. Matern. Fetal Neonatal Med. 2012. 25. 2575–2578.
48. Rab A., Szentpeteri I., Kornya L., Borzsonyi B., Demendi C., Joo J.G. Placental gene expression patterns of epidermal growth factor in intrauterine growth restriction // Eur. J. Obstet. Gynecol. Reprod. Biol. 2013. 170. (1). 96–99.
49. Radon-Pokracka M., Huras H., Jach R. Intrauterine growth restriction-diagnosis and treatment // Przegl. Lek. 2015. 72. (7). 376–382.
50. Radulescu L., Ferechide D., Popa F. The importance of fetal gender in intrauterine growth restriction // J. Med. Life. 2013. 6. (1). 38–39.
51. Raia-Barjat T., Prieux C., Gris J.C., Chapelle C., Laporte S., Chauleur C. Angiogenic factors for prediction of preeclampsia and intrauterine growth restriction onset in high-risk women: AngioPred study // J. Matern. Fetal Neonatal Med. 2017. 1–10. doi 10.1080/14767058.2017.1378325
52. Romero R., Erez O., Espinoza J., Fu W., Todem D., Kusanovic J.P., Gotsch F., Edwin S., Nien J.K., Chaiworapongsa T., Mittal P., Mazaki-Tovi S., Than N.G., Gomez R., Hassan S.S. The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age// J. Matern. Fetal Neonatal Med. 2008. 21. (5). 279–287.
53. Romero R., Nien J.K., Espinoza J., Todem D., Fu W., Chung H., Kusanovic J.P., Gotsch F., Erez O., Mazaki-Tovi S., Gomez R., Edwin S., Chaiworapongsa T., Levine R.J., Karumanchi S.A. A longitudinal study of angiogenic (placental growth factor) and antiangiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate // J. Matern. Fetal Neonatal Med. 2008. 21. (1). 9–23.
54. Rozance P.J., Anderson M., Martinez M., Fahy A., Macko A.R., Kailey J., Seedorf G.J., Abman S.H., Hay WW. Jr., Limesand S.W. Placental insufficiency decreases pancreatic vascularity and disrupts hepatocyte growth factor signaling in the pancreatic islet endothelial cell in fetal sheep // Diabetes. 2015. 64. (2). 555–564.
55. Schneider D., Hernandez C., Farias M., Uauy R., Krause B.J., Casanello P. Oxidative stress as common trait of endothelial dysfunction in chorionic arteries from fetuses with IUGR and LGA // Placenta. 2015. 36. 552–558.
56. Sharma D., Shastri S., Sharma P. Intrauterine growth restriction: Antenatal and postnatal aspects // Clin. Med. Insights: Pediatrics. 2016. 10. 67–83.
57. Stepan H., Krämer T., Faber R. Maternal plasma concentrations of soluble endoglin in pregnancies with intrauterine growth restriction// J. Clin. Endocrinol. Metab. 2007. 92. 2831–2834.
58. Suhag A., Berghella V. Intrauterine growth restriction (IUGR): etiology and diagnosis // Curr. Obstet. Gynecol. Rep. 2013. 2. 102–111.
59. Szentpeteri I., Rab A., Kornya L., Kovacs P., Brubel R., Joo J.G. Placental gene expression patterns of endoglin (CD105) in intrauterine growth restriction // J. Matern. Fetal Neonatal Med. 2014. 27. (4). 350–354.
60. Szentpeteri I., Rab A., Kornya L., Kovács P., Joo J.G. Gene expression patterns of vascular endothelial growth factor (VEGF-A) in human placenta from pregnancies with intrauterine growth restriction // J. Matern. Fetal Neonatal Med. 2013. 26. 984–9899
61. Wachter R., Masarik L., Burzle M., Mallik A., von Mandach U. Differential expression and activity of 11beta-hydroxysteroid dehydrogenase in human placenta and fetal membranes from pregnancies with intrauterine growth restriction // Fetal Diagn Ther. 2009. 25. 328–335.
62. Wixey J.A., Chand K.K., Colditz P.B., Bjorkman S.T. Neuroinflammation in intrauterine growth restriction // Placenta. 2017. 54. 117–124.
63. Wu F., Tian F.-J., Lin Y., Xu W.-M. Oxidative stress: placenta function and dysfunction // Am. J. Reprod. Immunol. 2016. 76. 258–271.
64. Toutain J., Prochazkova-Carlotti M., Cappellen D., Jarne A., Chevret E., Ferre J., Idrissi Y., Pelluard F., Carles D., Maugey-Laulon B., Lacombe D., Horovitz J., Merlio J.P., Saura R. Reduced placental telomere length during pregnancies complicated by intrauterine growth restriction // PLoS One. 2013. 8. (1). e54013.
65. Tzschoppe A., Struwe E., Blessing H., Fahlbusch F., Liebhaber G., Dörr H.G., Rauh M., Rascher W., Goecke T.W., Schild R.L., Schleussner E., Scheler C., Hübler A., Dahlem P., Dötsch J. Placental 11beta-HSD2 gene expression at birth is inversely correlated with growth velocity in the first year of life after intrauterine growth restriction // Pediatr. Res. 2009. 65. (6). 647–53.
66. Vahatalo R., Asikainen T.M., Karikoski R., Kinnula V.L., White C.W., Andersson S., Heikinheimo M., Myllarniemi M. Expression of transcription factor GATA-6 in alveolar epithelial cells is linked to neonatal lung disease // Neonatology. 2010. 9. 9. (3). 231–240.
67. Vattam K.K., Ali Khan I., Movva S., Mukkavali K.K., Upendram P., Poornima S., Rao P., Hasan Q. IGF2 ApaI A/G polymorphism evaluated in ESRD individuals as a biomarker to identify patients with new onset diabetes mellitus after renal transplant in Asian Indians // Open J. Nephrol. 2013. 3. 104–108.
68. Ye J., Zheng R., Wang Q., Liao L., Ying Y., Lu H., Cianflone K., Ning Q., Luo X. Down regulating SOCS3 with siRNA ameliorates insulin signaling and glucose metabolism in hepatocytes of IUGR rats with catch-up growth // Pediatr. Res. 2012. 72. (6). 550–559.
Долгова Н.С. – аспирант кафедры акушерства и гинекологии с курсом ДПО, e-mail: dolgovans@yandex.ru
