Clinicopathological Insights to the Nerve Growth Factor NGF Associated Stress Response in Pregnancy and Therapeutic Potential in Fetal Neurodevelopment: Clinicopathological Insights to the Nerve Growth Factor Associated Stress Response in Pregnancy

Tayyaba Siddique; Sahrish Bhutto; Naeemullah Syed; Muhammad Azam Javaid; Ayesha Zubair; Seemi Tanvir; Haseeb Khaliq

doi:10.54393/pjhs.v5i09.2249

Authors

Tayyaba Siddique Department of Gynaecology and Obstetrics, Tehsil Headquarters Hospital Wazirabad, Gujranwala, Pakistan
Sahrish Bhutto Department of Paediatrics, Dr Ziauddin Hospital, Karachi, Pakistan
Naeemullah Syed Department of Neurology, Federal Postgraduate Medical Institute, Lahore, Pakistan
Muhammad Azam Javaid Child Specialist, Hayat Memorial Teaching Hospital, Lahore, Pakistan
Ayesha Zubair Department of Biochemistry, Combined Military Hospital Lahore Medical College and Institute of Dentistry, Lahore, Pakistan
Seemi Tanvir Department of Pathology, Margalla Institute of Health Sciences, Rawalpindi, Pakistan
Haseeb Khaliq Department of Pathology, University of Health Sciences, Lahore, Pakistan

DOI:

https://doi.org/10.54393/pjhs.v5i09.2249

Keywords:

Nerve Growth Factor, Pregnancy, Maternal Stress, Fetal Neurodevelopment

Abstract

The nerve growth factor has a significant role in fetal neurogenesis and sustaining pregnancy. Objectives: To investigate the effects of nerve growth factor in stress response during pregnancy on developing fetus to bring clinicopathological correlation on the role of nerve growth factor in maternal stress markers (cortisol levels, glucocorticoids, depression, anxiety, and brain-derived neurotrophic factor levels) and fetal brain development. Methods: Following PRISMA guidelines, this study was extracted from PubMed, ScienceDirect, Nature, and Google Scholar articles from January 2014 to April 2024. The examination of pregnant women in published research gave a possibility to understand the application of nerve growth factor as a suitable biomarker for brain stress and fetal neuronal development. To exclude studies with lower ranks, each of the selected studies was assessed for adherence to evidence-based research methodology. The studies were taken from China, Europe, America and South Asia (including Pakistan). Results: Increased nerve growth factor levels were associated with maternal stress reactions which caused changes in cortisol levels and the amygdaloidal complex area. However, the increased nerve growth factor level was linked to changes in the fetal brain such as the weight of the fetal brain and stress biomarkers in the amniotic fluid sample inferring a critical role in the modulation of maternal stress on the fetal neurodevelopmental spheres. Conclusions: It was concluded that it is important to note how stress and nerve growth factors interact during pregnancy to create effective interventions to reduce stress dependence for the better health of both the mother and child.

References

Dhobale M, Mehendale S, Pisal H, Nimbargi V, Joshi S. Reduced Maternal and Cord Nerve Growth Factor Levels in Preterm Deliveries. International Journal of Developmental Neuroscience. 2012 Apr; 30(2): 99-103. doi: 10.1016/j.ijdevneu.2011.12.007. DOI: https://doi.org/10.1016/j.ijdevneu.2011.12.007

Tometten M, Blois S, Arck PC. Nerve Growth Factor in Reproductive Biology: The Link Between the Immune, Endocrine and Nervous System? Immunology of Pregnancy. 2005; 89: 135-48. doi: 10.1159/000087962. DOI: https://doi.org/10.1159/000087962

Tometten M, Blois S, Kuhlmei A, Stretz A, Klapp BF, Arck PC. Nerve Growth Factor Translates Stress Response and Subsequent Murine Abortion Via Adhesion Molecule-Dependent Pathways. Biology of Reproduction. 2006 Apr; 74(4): 674-83. doi: 10.1095/biolreprod.105.044651. DOI: https://doi.org/10.1095/biolreprod.105.044651

Dhobale M. Neurotrophins: Role in Adverse Pregnancy Outcome. International Journal of Developmental Neuroscience. 2014 Oct; 37: 8-14. doi: 10.1016/j.ijdevneu.2014.06.005. DOI: https://doi.org/10.1016/j.ijdevneu.2014.06.005

Wu Y, Espinosa KM, Barnett SD, Kapse A, Quistorff JL, Lopez C et al. Association of Elevated Maternal Psychological Distress, Altered Fetal Brain, and Offspring Cognitive and Social-Emotional Outcomes at 18 Months. Journal of the American Medical Association Network Open. 2022 Apr; 5(4): e229244-. doi: 10.1001/jamanetworkopen.2022.9244. DOI: https://doi.org/10.1001/jamanetworkopen.2022.9244

Lubrano C, Parisi F, Cetin I. Impact of Maternal Environment and Inflammation on Fetal Neurodevelopment. Antioxidants. 2024 Apr; 13(4): 453. doi: 10.3390/antiox13040453. DOI: https://doi.org/10.3390/antiox13040453

Wu Y, De Asis-Cruz J, Limperopoulos C. Brain Structural and Functional Outcomes in the Offspring of Women Experiencing Psychological Distress During Pregnancy. Molecular Psychiatry. 2024 Feb: 1-8. doi: 10.1038/s41380-024-02449-0. DOI: https://doi.org/10.1038/s41380-024-02449-0

García-Blanco A, Monferrer A, Grimaldos J, Hervás D, Balanzá-Martínez V, Diago V et al. A Preliminary Study to Assess the Impact of Maternal Age on Stress-Related Variables in Healthy Nulliparous Women. Psychoneuroendocrinology. 2017 Apr; 78: 97-104. doi: 10.1016/j.psyneuen.2017.01.018. DOI: https://doi.org/10.1016/j.psyneuen.2017.01.018

Zhang L, Huang R, Lei J, Liu Y, Liu D. Factors Associated with Stress Among Pregnant Women with a Second Child in Hunan Province Under China’s Two-child Policy: A Mixed-Method Study. BioMed Central Psychiatry. 2024 Feb; 24(1): 157. doi: 10.1186/s12888-024-05604-7. DOI: https://doi.org/10.1186/s12888-024-05604-7

Kazi A, Fatmi Z, Hatcher J, Niaz U, Aziz A. Development of a Stress Scale for Pregnant Women in the South Asian context: the AZ Stress Scale. Eastern Mediterranean Health Journal. 2009: 15(2): 353-361. doi: 10.26719/2009.15.2.353. DOI: https://doi.org/10.26719/2009.15.2.353

Graham AM, Doyle O, Tilden EL, Sullivan EL, Gustafsson HC, Marr M et al. Effects of Maternal Psychological Stress During Pregnancy on Offspring Brain Development: Considering the Role of Inflammation and Potential for Preventive Intervention. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2022 May; 7(5): 461-70. doi: 10.1016/j.bpsc.2021.10.012. DOI: https://doi.org/10.1016/j.bpsc.2021.10.012

D'souza V, Kilari A, Pisal H, Patil V, Mehendale S, Wagh G et al. Maternal Nerve Growth Factor Levels During Pregnancy in Women with Preeclampsia: A Longitudinal Study. International Journal of Developmental Neuroscience. 2015 Dec; 47: 340-6. doi: 10.1016/j.ijdevneu.2015.08.003. DOI: https://doi.org/10.1016/j.ijdevneu.2015.08.003

Sánchez-Infantes D, Cereijo R, Sebastiani G, Pérez-Cruz M, Villarroya F, Ibáñez L. Nerve Growth Factor Levels in Term Human Infants: Relationship to Prenatal Growth and Early Postnatal Feeding. International Journal of Endocrinology. 2018 Dec; 2018(1): 7562702. doi: 10.1155/2018/7562702. DOI: https://doi.org/10.1155/2018/7562702

Guo X, Jiang S, Xu J, Tian Y, Ouyang F, Yu X et al. Effects of Single and Combined Exposure to Lead and Stress During Pregnancy on Offspring Neurodevelopment. Developmental Cognitive Neuroscience. 2022 Aug; 56: 101124. doi: 10.1016/j.dcn.2022.101124. DOI: https://doi.org/10.1016/j.dcn.2022.101124

Machairiotis N, Vrachnis D, Antonakopoulos N, Loukas N, Fotiou A, Pergialiotis V et al. Detection and Quantification of Neurotrophin-3 (NT-3) and Nerve Growth Factor (NGF) Levels in Early Second Trimester Amniotic Fluid: Investigation into a Possible Correlation with Abnormal Fetal Growth Velocity Patterns. Journal of Clinical Medicine. 2023 Jun; 12(12): 4131. doi: 10.3390/jcm12124131. DOI: https://doi.org/10.3390/jcm12124131

Akbaba N, Annagür BB, Annagür A, Akbulut H, Akyürek F, Çelık Ç. Neurotrophins and Neuroinflammation in Fetuses Exposed to Maternal Depression and Anxiety Disorders During Pregnancy: A Comparative Study on Cord Blood. Archives of Women's Mental Health. 2018 Feb; 21: 105-11. doi: 10.1007/s00737-017-0774-1. DOI: https://doi.org/10.1007/s00737-017-0774-1

Flöck A, Weber SK, Ferrari N, Fietz C, Graf C, Fimmers R et al. Determinants of Brain-Derived Neurotrophic Factor (BDNF) in Umbilical Cord and Maternal Serum. Psychoneuroendocrinology. 2016 Jan; 63: 191-7. doi: 10.1016/j.psyneuen.2015.09.028. DOI: https://doi.org/10.1016/j.psyneuen.2015.09.028

Lamadé EK, Pedraz-Petrozzi B, Lindner O, Meininger P, Pisters A, Gilles M et al. Stress in Pregnancy-Implications for Fetal BDNF in Amniotic Fluid at Birth. Neurobiology of Stress. 2024 Jun; 32: 100658. doi: 10.1016/j.ynstr.2024.100658. DOI: https://doi.org/10.1016/j.ynstr.2024.100658

Walsh K, McCormack CA, Webster R, Pinto A, Lee S, Feng T et al. Maternal Prenatal Stress Phenotypes Associate with Fetal Neurodevelopment and Birth Outcomes. Proceedings of the National Academy of Sciences. 2019 Nov; 116(48): 23996-4005. doi: 10.1073/pnas.1905890116. DOI: https://doi.org/10.1073/pnas.1905890116

Aisa MC, Barbati A, Cappuccini B, De Rosa F, Gerli S, Clerici G et al. Urinary Nerve Growth Factor in Full-Term, Preterm and Intra Uterine Growth Restriction Neonates: Association with Brain Growth at 30–40 Days of Postnatal Period and with Neuro-Development Outcome at Two Years. A Pilot Study. Neuroscience Letters. 2021 Jan; 741: 135459. doi: 10.1016/j.neulet.2020.135459. DOI: https://doi.org/10.1016/j.neulet.2020.135459

Walsh J, Palandra J, Goihberg E, Deng S, Hurst S, Neubert H. Analysis of β-nerve Growth Factor and Its Precursor During Human Pregnancy by Immunoaffinity-Liquid Chromatography-Tandem Mass Spectrometry. Scientific Reports. 2023 Jun; 13(1): 9180. doi: 10.1038/s41598-023-34695-7. DOI: https://doi.org/10.1038/s41598-023-34695-7

Zhang T, Wang H, Ouyang F, Yang H, Zhang J, Zhang N. Does Brain-Derived Neurotrophic Factor Play a Role in the Association Between Maternal Prenatal Mental Health and Neurodevelopment in 2-Year-Old Children? Journal of Affective Disorders. 2024 Aug; 359: 171-9. doi: 10.1016/j.jad.2024.05.074. DOI: https://doi.org/10.1016/j.jad.2024.05.074

Uncu GS, Karayağmurlu A, Kaynar TB, Baki AM, Vural P, Soylu N. Serum Levels of Brain-Derived Neurotrophic Factor, Nerve Growth Factor, Neurotrophin-3, and Glial-Derived Neurotrophic Factor in Children with Specific Learning Disorder. Archives of Neuropsychiatry. 2022 Nov; 59(4): 260. doi: 10.29399/npa.28043. DOI: https://doi.org/10.29399/npa.28043

Lu YC, escavage N, Wu Y, Kapse K, Andersen NR, Quistorff J et al. Maternal Psychological Distress During the COVID-19 Pandemic and Structural Changes of the Human Fetal Brain. Communications Medicine. 2022 May; 2(1): 47. doi: 10.1038/s43856-022-00111-w. DOI: https://doi.org/10.1038/s43856-022-00111-w

Scheinost D, Spann MN, McDonough L, Peterson BS, Monk C. Associations Between Different Dimensions of Prenatal Distress, Neonatal Hippocampal Connectivity, and Infant Memory. Neuro psychopharmacology. 2020 Jul; 45(8): 1272-9. doi: 10.1038/s41386-020-0677-0. DOI: https://doi.org/10.1038/s41386-020-0677-0

Lehtola SJ, Tuulari JJ, Scheinin NM, Karlsson L, Parkkola R, Merisaari H et al. New Born Amygdalar Volumes are Associated with Maternal Prenatal Psychological Distress in a Sex-Dependent Way. NeuroImage: Clinical. 2020 Jan; 28: 102380. doi: 10.1016/j.nicl.2020.102380. DOI: https://doi.org/10.1016/j.nicl.2020.102380

Massaro AN, Rothbaum R, Aly H. Fetal Brain Development: The Role of Maternal Nutrition, Exposures and Behaviors. Journal of Pediatric Neurology. 2006 Mar; 4(01): 001-9. doi: 10.1055/s-0035-1557300. DOI: https://doi.org/10.1055/s-0035-1557300

Fenster T, Rao M, Mamzhi Y, Tsou Jr H. Fetal Neurobehavioral Development: The Role of Maternal Psychosocial, Pathological, and Pharmacological Stress. Georgetown Medical Review. 2020 May; 4(1). doi: 10.52504/001c.12642. DOI: https://doi.org/10.52504/001c.12642

Ceci FM, Ferraguti G, Petrella C, Greco A, Tirassa P, Iannitelli A et al. Nerve Growth Factor, Stress and Diseases. Current Medicinal Chemistry. 2021 May; 28(15): 2943-59. doi: 10.2174/0929867327999200818111654. DOI: https://doi.org/10.2174/0929867327999200818111654

Cirulli F and Alleva E. The NGF Saga: From Animal Models of Psychosocial Stress to Stress-Related Psychopathology. Frontiers in Neuroendocrinology. 2009 Aug; 30(3): 379-95. doi: 10.1016/j.yfrne.2009.05.002. DOI: https://doi.org/10.1016/j.yfrne.2009.05.002

Zoumakis E, Kalantaridou SN, Chrousos GP. The “Brain–Skin Connection”: Nerve Growth Factor-Dependent Pathways for Stress-Induced Skin Disorders. Journal of Molecular Medicine. 2007 Dec; 85: 1347-9. doi: 10.1007/s00109-007-0270-6. DOI: https://doi.org/10.1007/s00109-007-0270-6

Alleva E, Petruzzi S, Cirulli F, Aloe L. NGF Regulatory Role in Stress and Coping of Rodents and Humans. Pharmacology Biochemistry and Behavior. 1996 May; 54(1): 65-72. doi: 10.1016/0091-3057(95)02111-6. DOI: https://doi.org/10.1016/0091-3057(95)02111-6

Nilsen-Hamilton M. Growth Factor Signaling in Early Mammalian Development. In growth Factors in Mammalian Development. CRC Press. 2021 May: 135-166. doi: 10.1201/9781003210351-8. DOI: https://doi.org/10.1201/9781003210351-8

Lobos E, Gebhardt C, Kluge A, Spanel-Borowski K. Expression of Nerve Growth Factor (NGF) Isoforms in the Rat Uterus During Pregnancy: Accumulation of Precursor proNGF. Endocrinology. 2005 Apr; 146(4): 1922-9. doi: 10.1210/en.2004-0925. DOI: https://doi.org/10.1210/en.2004-0925

Al-Yozbaki M, Acha-Sagredo A, George A, Liloglou T, Wilson CM. Balancing Neurotrophin Pathway and Sortilin Function: Its Role in Human Disease. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2020 Dec; 1874(2): 188429. doi: 10.1016/j.bbcan.2020.188429. DOI: https://doi.org/10.1016/j.bbcan.2020.188429

Dou SH, Cui Y, Huang SM, Zhang B. The Role of Brain-Derived Neurotrophic Factor Signaling in Central Nervous System Disease Pathogenesis. Frontiers in Human Neuroscience. 2022 Jun; 16: 924155. doi: 10.3389/fnhum.2022.924155. DOI: https://doi.org/10.3389/fnhum.2022.924155

Capossela L, Gatto A, Ferretti S, Di Sarno L, Graglia B, Massese M et al. Multifaceted Roles of Nerve Growth Factor: A Comprehensive Review with a Special Insight into Pediatric Perspectives. Biology. 2024 Jul; 13(7): 546. doi: 10.3390/biology13070546. DOI: https://doi.org/10.3390/biology13070546

Li R, Li DH, Zhang HY, Wang J, Li XK, Xiao J. Growth Factors-Based Therapeutic Strategies and Their Underlying Signaling Mechanisms for Peripheral Nerve Regeneration. Acta Pharmacologica Sinica. 2020 Oct; 41(10): 1289-300. doi: 10.1038/s41401-019-0338-1. DOI: https://doi.org/10.1038/s41401-019-0338-1

Sims SK, Wilken-Resman B, Smith CJ, Mitchell A, McGonegal L, Sims-Robinson C. Brain‐derived Neurotrophic Factor and Nerve Growth Factor Therapeutics for Brain Injury: The Current Translational Challenges in Preclinical and Clinical Research. Neural Plasticity. 2022 Mar; 2022(1): 3889300. doi: 10.1155/2022/3889300. DOI: https://doi.org/10.1155/2022/3889300

Sahay A, Kale A, Joshi S. Role of Neurotrophins in Pregnancy and Offspring Brain Development. Neuropeptides. 2020 Oct; 83: 102075. doi:10.1016/j.npep.2020.102075. DOI: https://doi.org/10.1016/j.npep.2020.102075

Ciafrè S, Ferraguti G, Tirassa P, Iannitelli A, Ralli M, Greco A et al. Nerve Growth Factor in the Psychiatric Brain. Rivista di psichiatria. 2020; 55(1) :4-15.

Xhima K and Aubert I. The Therapeutic Potential of Nerve Growth Factor Combined with Blood-Brain Barrier Modulation by Focused Ultrasound for Neurodegenerative Disorders. Neural Regeneration Research. 2021 Sep; 16(9): 1783-5. doi: 10.4103/1673-5374.306076. DOI: https://doi.org/10.4103/1673-5374.306076