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Fetal exposure to prenatal stress can impede optimum brain development and deranged mother\u2019s hypothalamic\u2013pituitary\u2013adrenal axis (HPA axis) stress responses can alter the neurodevelopmental trajectories of the offspring. Corticotropin-releasing hormone (CRH) and glucocorticoids, regulate fetal neurogenesis and while CRH exerts neuroprotective actions, increased levels of stress hormones have been associated with fetal brain structural alterations such as reduced cortical volume, impoverishment of neuronal density in the limbic brain areas and alterations in neuronal circuitry, synaptic plasticity, neurotransmission and G-protein coupled receptor (GPCR) signalling. Emerging evidence highlight the role of epigenetic changes in fetal brain programming, as stress-induced methylation of genes encoding molecules that are implicated in HPA axis and major neurodevelopmental processes. These serve as molecular memories and have been associated with long term modifications of the offspring\u2019s stress regulatory system and increased susceptibility to psychosomatic disorders later in life. This review summarises our current understanding on the roles of CRH and other mediators of stress responses on fetal neurodevelopment.<\/jats:p>","DOI":"10.3389\/fendo.2021.714214","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T04:59:52Z","timestamp":1627880392000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":54,"title":["Placental CRH as a Signal of Pregnancy Adversity and Impact on Fetal Neurodevelopment"],"prefix":"10.3389","volume":"12","author":[{"given":"Ifigeneia","family":"Kassotaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Valsamakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Mastorakos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitris K.","family":"Grammatopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,2]]},"reference":[{"key":"B1","unstructured":"House Commons, Heal Soc Care Comm13th Report: Session 2017-20192019"},{"key":"B2","doi-asserted-by":"publisher","first-page":"100739","DOI":"10.1016\/j.yfrne.2019.02.003","article-title":"Giving a Good Start to a New Life via Maternal Brain Allostatic Adaptations in Pregnancy","volume":"53","author":"Russell","year":"2019","journal-title":"Front Neuroendocrinol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.2399\/ana.09.034","article-title":"Effects of Prenatal Stress on Developmental Anatomy of the Brain and Adult Behavioural Pathology","volume":"3","author":"Ulup\u0131nar","year":"2009","journal-title":"Anat (Int J Exp Clin Anat)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1159\/000488468","article-title":"Early-Life Stress: From Neuroendocrine Mechanisms to Stress-Related Disorders","volume":"89","author":"Pervanidou","year":"2018","journal-title":"Horm Res Paediatr"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1003","article-title":"Developmental Programming, a Pathway to Disease","volume":"157","author":"Padmanabhan","year":"2016","journal-title":"Endocrinology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/dev.20316","article-title":"Influence of Prenatal Psychosocial Stress on Cytokine Production in Adult Women","volume":"50","author":"Entringer","year":"2008","journal-title":"Dev Psychobiol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3109\/10253890.2013.876404","article-title":"Prenatal Maternal Stress Exposure and Immune Function in the Offspring","volume":"17","author":"Veru","year":"2014","journal-title":"Int J Biol Stress"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011896","article-title":"Prenatal Stress Exposure Related to Maternal Bereavement and Risk of Childhood Overweight","volume":"5","author":"Li","year":"2010","journal-title":"PloS One"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2008.03.006","article-title":"Prenatal Psychosocial Stress Exposure Is Associated With Insulin Resistance in Young Adults","volume":"199","author":"Entringer","year":"2008","journal-title":"Am J Obstet Gynecol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2020.104591","article-title":"Maternal Chronic Stress Correlates With Serum Levels of Cortisol, Glucose and C-Peptide in the Fetus, and Maternal Non Chronic Stress With Fetal Growth","volume":"114","author":"Valsamakis","year":"2020","journal-title":"Psychoneuroendocrinology"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2015.08.003","article-title":"Neuroactive Steroids and Stress Axis Regulation: Pregnancy and Beyond","volume":"160","author":"Brunton","year":"2016","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301450","article-title":"Antenatal Maternal Anxiety Is Related to HPA-Axis Dysregulation and Self-Reported Depressive Symptoms in Adolescence: A Prospective Study on the Fetal Origins of Depressed Mood","volume":"33","author":"Van Den Bergh","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.180.6.502","article-title":"Maternal Antenatal Anxiety and Children\u2019s Behavioural\/Emotional Problems at 4 Years. 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