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The impact of the placenta on neuropsychic development of the fetus

https://doi.org/10.46563/1560-9561-2025-28-5-373-379

EDN: mvcmdv

Abstract

Introduction. The placenta is a key organ that determines the conditions of fetal development and neuropsychological health. It performs endocrine, metabolic, and barrier functions, regulates the supply of oxygen, nutrients, and hormones and protects the fetus from xenobiotics and pathogens. The aim of this review is to determine the interactions between the placenta and the fetal nervous system and the potential impact of their disorders on the further neuropsychological development of the fetus. The literature search was conducted in the Embase, PubMed, Google Scholar, and Medline databases. Placental process disorders lead to hypoxia, inflammation, and endocrine imbalances, which are associated with fetal growth restriction, preterm birth, and central nervous system damage. Placental infection (chorioamnionitis) further increases cytokine exposure, causes epigenetic changes, and is associated with the risk of psychiatric disorders, including attention deficit hyperactivity disorder, autism, and schizophrenia. Placental insufficiency is accompanied by blood flow remodeling, mitochondrial dysfunction, and activation of inflammatory cascades, which contribute to the development of gliosis and impaired neuronal differentiation. The endocrine role of the placenta is manifested in the synthesis of neurosteroids (allopregnanolone, which plays a multifaceted role in the development of the central nervous system), the regulation of glucocorticoid levels, and the transport of thyroid hormones. These factors are critical for myelination, synaptic formation, and the emotional and cognitive stability of the fetus. Imbalances in these factors are associated with cortical thinning, impaired sensory processing, and behavioral disorders in the fetus. An additional mechanism of placental effect is the subcellular transport of microRNAs and extracellular vesicles involved in epigenetic regulation. These molecules are considered as promising biomarkers for early detection of cognitive and motor disorders in the fetus.

Contribution:
Sibirskaya E.V., Sharkov S.M., Ivannikov N.Yu. — study concept and design, data analysis, editing the text;
Aigistova N.M., Gorshkova D.V. — data collection, processing, analysis, writing the text;
Sibirskaya E.V. — editing the text.
All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgment. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: September 10, 2025
Accepted: October 02, 2025
Published: October 30, 2025

About the Authors

Elena V. Sibirskaya
Russian Children’s Clinical Hospital — branch of the Pirogov Russian National Research Medical University (Pirogov University); Pirogov Russian National Research Medical University (Pirogov University); Russian University of Medicine
Russian Federation

MD, Ph.D., prof., Department of obstetrics, gynecology and reproductive medicine, Pirogov Russian National Research Medical University; Prof., Department of obstetrics and gynecology named after Academician G.M. Saveleva, Pirogov University; Head, Surgical gynecology department, Russian Children’s Clinical Hospital, Pirogov University

e-mail: elsibirskaya@yandex.ru



Sergey M. Sharkov
Morozovskaya Children Municipal Clinical Hospital; I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation


Nikolai Yu. Ivannikov
Pirogov Russian National Research Medical University (Pirogov University); Dolgoprudennskaya Hospital
Russian Federation


Nina M. Aigistova
Pirogov Russian National Research Medical University (Pirogov University)
Russian Federation


Daria V. Gorshkova
Pirogov Russian National Research Medical University (Pirogov University)
Russian Federation


References

1. Cindrova-Davies T., Sferruzzi-Perri A.N. Human placental development and function. Semin Cell Dev. Biol. 2022; 131: 66–77. https://doi.org/10.1016/j.semcdb.2022.03.039

2. Khorami-Sarvestani S., Vanaki N., Shojaeian S., Zarnani K., Stensballe A., Jeddi-Tehrani M., et al. Placenta: an old organ with new functions. Front. Immunol. 2024; 15: 1385762. https://doi.org/10.3389/fimmu.2024.1385762

3. Shah D.K., Pereira S., Lodygensky G.A. Long-term neurologic consequences following Fetal growth restriction: the impact on brain reserve. Dev. Neurosci. 2025; 47(2): 139–46. https://doi.org/10.1159/000539266

4. Lazzara A., Boss R.D. Ethical complexities of neonatal neurocritical care. Clin. Perinatol. 2025; 52(2): 439–48. https://doi.org/10.1016/j.clp.2025.02.014

5. Meenai Z.M., Nair M.K.C., Dalwai S., Nair L.D.V., Gulati S., Mukherjee S.B., et al. Consensus guidelines of the Indian Academy of Pediatrics (IAP)-neurodevelopmental pediatrics chapter on developmentally supportive follow-up for high-risk infants. Indian Pediatr. 2025; 62(8): 638–9. https://doi.org/10.1007/s13312-025-00128-z

6. Wang P., Zhou Y., Zhao Y., Zhao W., Wang H., Li J., et al. Prenatal fine particulate matter exposure associated with placental small extracellular vesicle derived microRNA and child neurodevelopmental delays. Sci. Total. Environ. 2022; 841: 156747. https://doi.org/10.1016/j.scitotenv.2022.156747

7. Tsechoeva T.K., Burdukova Yu.A., Lenyushkina A.A., Degtyarev D.N. Comparison of methods for assessing the psychomotor development of preterm infants born with extremely low birth weight and very low birth weight. Neonatologiya: novosti, mneniya, obuchenie. 2025; 13(1): 32–40. https://doi.org/10.33029/2308-2402-2025-13-1-32-40 https://elibrary.ru/hcsfvi (in Russian)

8. Hussain T., Murtaza G., Metwally E., Kalhoro D.H., Kalhoro M.S., Rahu B.A., et al. The role of oxidative stress and antioxidant balance in pregnancy. Mediators Inflamm. 2021; 2021: 9962860. https://doi.org/10.1155/2021/9962860

9. Aplin J.D., Myers J.E., Timms K., Westwood M. Tracking placental development in health and disease. Nat. Rev. Endocrinol. 2020; 16(9): 479–94. https://doi.org/10.1038/s41574-020-0372-6

10. Sun C., Groom K.M., Oyston C., Chamley L.W., Clark A.R., James J.L. The placenta in fetal growth restriction: What is going wrong? Placenta. 2020; 96: 10–8. https://doi.org/10.1016/j.placenta.2020.05.003

11. Colson A., Sonveaux P., Debiève F., Sferruzzi-Perri A.N. Adaptations of the human placenta to hypoxia: opportunities for interventions in fetal growth restriction. Hum. Reprod. Update. 2021; 27(3): 531–69. https://doi.org/10.1093/humupd/dmaa053

12. Melchiorre K., Giorgione V., Thilaganathan B. The placenta and preeclampsia: villain or victim? Am. J. Obstet. Gynecol. 2022; 226(2S): 954–62. https://doi.org/10.1016/j.ajog.2020.10.024

13. Simone N., Campagnolo L., Fazleabas A. Clinical consequences of defective decidualization. Tissue Cell. 2021; 72: 101586. https://doi.org/10.1016/j.tice.2021.101586

14. Zur R.L., Kingdom J.C., Parks W.T., Hobson S.R. The placental basis of fetal growth restriction. Obstet. Gynecol. Clin. North Am. 2020; 47(1): 81–98. https://doi.org/10.1016/j.ogc.2019.10.008

15. Ahmadzadeh E., Polglase G.R., Stojanovska V., Herlenius E., Walker D.W., Miller S.L., et al. Does fetal growth restriction induce neuropathology within the developing brainstem? J. Physiol. 2023; 601(21): 4667–89. https://doi.org/10.1113/JP284191

16. Ali S., Kawooya M.G., Byamugisha J., Kakibogo I.M., Biira E.A., Kagimu A.N., et al. Middle cerebral arterial flow redistribution is an indicator for intrauterine fetal compromise in late pregnancy in low-resource settings: A prospective cohort study. BJOG. 2022; 129(10): 1712–20. https://doi.org/10.1111/1471-0528.17115

17. Oros D., Figueras F., Cruz-Martinez R., Padilla N., Meler E., Hernandez-Andrade E., et al. Middle versus anterior cerebral artery Doppler for the prediction of perinatal outcome and neonatal neurobehavior in term small-for-gestational-age fetuses with normal umbilical artery Doppler. Ultrasound Obstet. Gynecol. 2010; 35(4): 456–61. https://doi.org/10.1002/uog.7588

18. Ostrem B.E.L., Domínguez-Iturza N., Stogsdill J.A., Faits T., Kim K., Levin J.Z., et al. Fetal brain response to maternal inflammation requires microglia. Development. 2024; 151(10): dev202252. https://doi.org/10.1242/dev.202252

19. Woods R.M., Lorusso J.M., Fletcher J., ElTaher H., McEwan F., Harris I., et al. Maternal immune activation and role of placenta in the prenatal programming of neurodevelopmental disorders. Neuronal Signal. 2023; 7(2): NS20220064. https://doi.org/10.1042/NS20220064

20. Sahay A., Kale A., Joshi S. Role of neurotrophins in pregnancy and offspring brain development. Neuropeptides. 2020; 83: 102075. https://doi.org/10.1016/j.npep.2020.102075

21. Chen S., Shenoy A. Placental pathology and the developing brain. Semin. Pediatr. Neurol. 2022; 42: 100975. https://doi.org/10.1016/j.spen.2022.100975

22. Briana D.D., Malamitsi-Puchner A. Chorioamnionitis in utero, schizophrenia in adulthood: limited current evidence-future research focus? J. Matern. Fetal. Neonatal. Med. 2022; 35(24): 4782–7. https://doi.org/10.1080/14767058.2020.1863370

23. Redline R.W., Roberts D.J., Parast M.M., Ernst L.M., Morgan T.K., Greene M.F., et al. Placental pathology is necessary to understand common pregnancy complications and achieve an improved taxonomy of obstetrical disease. Am. J. Obstet. Gynecol. 2023; 228(2): 187–202. https://doi.org/10.1016/j.ajog.2022.08.010

24. Vacher C.M., Bonnin A., Mir I.N., Penn A.A. Advances and perspectives in neuroplacentology. Front. Endocrinol. (Lausanne). 2023; 14: 1206072. https://doi.org/10.3389/fendo.2023.1206072

25. Yates N., Gunn A.J., Bennet L., Dhillon S.K., Davidson J.O. Preventing brain injury in the preterm infant-current controversies and potential therapies. Int. J. Mol. Sci. 2021; 22(4): 1671. https://doi.org/10.3390/ijms22041671

26. Ng N.S., Razak A., Chandrasekharan P., McLean G., Sackett V., Zhou L., et al. Early neurodevelopmental outcomes of preterm infants with intraventricular haemorrhage and periventricular leukomalacia. J. Paediatr. Child Health. 2024; 60(11): 669–74. https://doi.org/10.1111/jpc.16654

27. Song I.G. Neurodevelopmental outcomes of preterm infants. Clin. Exp. Pediatr. 2023; 66(7): 281–7. https://doi.org/10.3345/cep.2022.00822

28. Lautarescu A., Craig M.C., Glover V. Prenatal stress: Effects on fetal and child brain development. Int. Rev. Neurobiol. 2020; 150: 17–40. https://doi.org/10.1016/bs.irn.2019.11.002

29. Musillo C., Berry A., Cirulli F. Prenatal psychological or metabolic stress increases the risk for psychiatric disorders: the “funnel effect” model. Neurosci. Biobehav. Rev. 2022; 136: 104624. https://doi.org/10.1016/j.neubiorev.2022.104624

30. Wang T., Chen S., Mao Z., Shang Y., Brinton R.D. Allopregnanolone pleiotropic action in neurons and astrocytes: calcium signaling as a unifying mechanism. Front. Endocrinol. (Lausanne). 2023; 14: 1286931. https://doi.org/10.3389/fendo.2023.1286931

31. Haraguchi S., Tsutsui K. Pineal neurosteroids: biosynthesis and physiological functions. Front. Endocrinol. (Lausanne). 2020; 11: 549. https://doi.org/10.3389/fendo.2020.00549

32. Shaw J.C., Crombie G.K., Palliser H.K., Hirst J.J. Impaired oligodendrocyte development following preterm birth: promoting GABAergic action to improve outcomes. Front. Pediatr. 2021; 9: 618052. https://doi.org/10.3389/fped.2021.618052

33. Schumacher M., Liere P., Ghoumari A. Progesterone and fetal-neonatal neuroprotection. Best Pract. Res. Clin. Obstet. Gynaecol. 2020; 69: 50–61. https://doi.org/10.1016/j.bpobgyn.2020.09.001

34. Mayer E., Winkler I., Huber E., Urbanek M., Kiechl-Kohlendorfer U., Griesmaier E., et al. Effects of DHEA and DHEAS in neonatal hypoxic-ischemic brain injury. Antioxidants (Basel). 2024; 13(12): 1542. https://doi.org/10.3390/antiox13121542

35. Vahidinia Z., Karimian M., Joghataei M.T. Neurosteroids and their receptors in ischemic stroke: From molecular mechanisms to therapeutic opportunities. Pharmacol. Res. 2020; 160: 105163. https://doi.org/10.1016/j.phrs.2020.105163

36. Hirst J.J., Palliser H.K., Pavy C., Shaw J.C., Moloney R.A. Neurosteroid replacement approaches for improving outcomes after compromised pregnancies and preterm birth. Front. Neuroendocrinol. 2025; 76: 101169. https://doi.org/10.1016/j.yfrne.2024.101169

37. Vacher C.M., Lacaille H., O’Reilly J.J., Salzbank J., Bakalar D., Sebaoui S., et al. Placental endocrine function shapes cerebellar development and social behavior. Nat. Neurosci. 2021; 24(10): 1392–401. https://doi.org/10.1038/s41593-021-00896-4

38. Bakalar D., O’Reilly J.J., Lacaille H., Salzbank J., Ellegood J., Lerch J.P., et al. Lack of placental neurosteroid alters cortical development and female somatosensory function. Front. Endocrinol. (Lausanne). 2022; 13: 972033. https://doi.org/10.3389/fendo.2022.972033

39. Crombie G.K., Palliser H.K., Shaw J.C., Hanley B.A., Moloney R.A., Hirst J.J. Prenatal stress induces translational disruption associated with myelination deficits. Dev. Neurosci. 2023; 45(5): 290–08. https://doi.org/10.1159/000530282

40. Eng L., Lam L. Thyroid function during the fetal and neonatal periods. Neoreviews. 2020; 21(1): 30–6. https://doi.org/10.1542/neo.21-1-30

41. Chen Y., Luo Z.C., Zhang T., Fan P., Ma R., Zhang J., et al. Maternal thyroid dysfunction and neuropsychological development in children. J. Clin. Endocrinol. Metab. 2023; 108(2): 339–50. https://doi.org/10.1210/clinem/dgac577

42. Thyroid Disease in Pregnancy: ACOG Practice Bulletin, Number 223. Obstet. Gynecol. 2020; 135(6): 261–74. https://doi.org/10.1097/AOG.0000000000003893

43. Adibi J.J., Xun X., Zhao Y., Yin Q., LeWinn K., Bush N.R., et al. Second-trimester placental and thyroid hormones are associated with cognitive development from ages 1 to 3 years. J. Endocr. Soc. 2021; 5(5): bvab027. https://doi.org/10.1210/jendso/bvab027

44. Adibi J.J., Zhao Y., Koistinen H., Mitchell R.T., Barrett E.S., Miller R., et al. Molecular pathways in placental-fetal development and disruption. Mol. Cell Endocrinol. 2024; 581: 112075. https://doi.org/10.1016/j.mce.2023.112075

45. Chen Z., van der Sman A.S.E., Groeneweg S., de Rooij L.J., Visser W.E., Peeters R.P., et al. Thyroid hormone transporters in a human placental cell model. Thyroid. 2022; 32(9): 1129–37. https://doi.org/10.1089/thy.2021.0503

46. Rosenfeld C.S. Placental serotonin signaling, pregnancy outcomes, and regulation of fetal brain development. Biol. Reprod. 2020; 102(3): 532–8. https://doi.org/10.1093/biolre/ioz204

47. Perić M., Bečeheli I., Čičin-Šain L., Desoye G., Štefulj J. Serotonin system in the human placenta — the knowns and unknowns. Front. Endocrinol. (Lausanne). 2022; 13: 1061317. https://doi.org/10.3389/fendo.2022.1061317

48. Karahoda R., Abad C., Horackova H., Kastner P., Zaugg J., Cerveny L., et al. Dynamics of tryptophan metabolic pathways in human placenta and placental-derived cells: effect of gestation age and trophoblast differentiation. Front. Cell Dev. Biol. 2020; 8: 574034. https://doi.org/10.3389/fcell.2020.574034

49. Bravo K., González-Ortiz M., Beltrán-Castillo S., Cáceres D., Eugenín J. Development of the placenta and brain are affected by selective serotonin reuptake inhibitor exposure during critical periods. Adv. Exp. Med. Biol. 2023; 1428: 179–98. https://doi.org/10.1007/978-3-031-32554-0_8

50. Portillo R., Abad C., Synova T., Kastner P., Heblik D., Kucera R., et al. Cannabidiol disrupts tryptophan metabolism in the human term placenta. Toxicology. 2024; 505: 153813. https://doi.org/10.1016/j.tox.2024.153813

51. Melnikova V., Lifantseva N., Voronova S., Bondarenko N. Prenatal stress modulates placental and fetal serotonin levels and determines behavior patterns in offspring of mice. Int. J. Mol. Sci. 2024; 25(24): 13565. https://doi.org/10.3390/ijms252413565

52. Hanswijk S.I., Spoelder M., Shan L., Verheij M.M.M., Muilwijk O.G., Li W., et al. Gestational factors throughout fetal neurodevelopment: the serotonin link. Int. J. Mol. Sci. 2020; 21(16): 5850. https://doi.org/10.3390/ijms21165850

53. Gumusoglu S., Scroggins S., Vignato J., Santillan D., Santillan M. The serotonin-immune Axis in preeclampsia. Curr. Hypertens. Rep. 2021; 23(7): 37. https://doi.org/10.1007/s11906-021-01155-4

54. Rosenfeld C.S. Placenta extracellular vesicles: messengers connecting maternal and fetal systems. Biomolecules. 2024; 14(8): 995. https://doi.org/10.3390/biom14080995

55. Su Z., Frost E.L., Lammert C.R., Przanowska R.K., Lukens J.R., Dutta A. tRNA-derived fragments and microRNAs in the maternal-fetal interface of a mouse maternal-immune-activation autism model. RNA Biol. 2020; 17(8): 1183–95. https://doi.org/10.1080/15476286.2020.1721047

56. Andjus P., Kosanović M., Milićević K., Gautam M., Vainio S.J., Jagečić D., et al. Extracellular vesicles as innovative tool for diagnosis, regeneration and protection against neurological damage. Int. J. Mol. Sci. 2020; 21(18): 6859. https://doi.org/10.3390/ijms21186859

57. Rank O. Das Тrauma der Geburt. Frankfurt am Main: Fischer; 1924.

58. Brekhman G.I. Emotional life of the fetus: from vague guesses to scientific research. Zhinochiy Likar. 2011; (2): 10–5. (in Russian)

59. Maldonado-Duran J.M., Lartique T., Feintuch M. Perinatal psychiatry: infant mental health interventions during pregnancy. Bull. Menninger. Clin. 2000; 64(3): 317–43.

60. Mulder E.J.H., Robles de Medina P.G., Huizink A.C., Van den Bergh B.R.N., Buitelaar J.K., Visser G.H.A. Prenatal maternal stress: effects on pregnancy and the (unborn) child. Early Hum. Dev. 2000; 70(1–2): 3–14. https://doi.org/10.1016/s0378-3782(02)00075-0

61. Whitaker R.C., Orzol S.M., Kahn R.S. Maternal mental health, substance use, and domestic violence in the year after delivery and subsequent behavior problems in children at age 3 years. Arch. Gen. Psychiatry. 2006; 63(5): 551–60. https://doi.org/10.1001/archpsyc.63.5.551

62. Brekhman G.I., Yagav R., Gonopolsky M.H., Tsibulevskaya M.Yu. Prenatal stress as a risk factor for development of schizophrenia and bipolar affective disorder. Vestnik Ivanovskoy meditsinskoy akademii. 2010; 15(1): 23–7. https://elibrary.ru/mbcsav (in Russian)


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Sibirskaya E.V., Sharkov S.M., Ivannikov N.Yu., Aigistova N.M., Gorshkova D.V. The impact of the placenta on neuropsychic development of the fetus. Russian Pediatric Journal. 2025;28(5):373-379. (In Russ.) https://doi.org/10.46563/1560-9561-2025-28-5-373-379. EDN: mvcmdv

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