Stress as an Endocrine Disruptor: Maternal Psychosocial Stress during Pregnancy and Fetal Development
1:00 pm US Eastern Time
Slides & Resources
Dr. Bale
O-GlcNAc transferase (OGT) as a placental biomarker of maternal stress and reprogramming of CNS gene transcription in development, Howerton CL, Morgan CP, Fischer DB, Bale TL. Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5169-74. doi: 10.1073/pnas.1300065110.
Antiinflammatory treatment ameliorates HPA stress axis dysfunction in a mouse model of stress sensitivity, Gerber AR, Bale TL. Endocrinology. 2012 Oct;153(10):4830-7. Epub 2012 Aug 14.
Prenatal programing: at the intersection of maternal stress and immune activation, Howerton CL, Bale TL. Horm Behav. 2012 Aug;62(3):237-42. doi: 10.1016/j.yhbeh.2012.03.007. Epub 2012 Mar 23. Review.
Early prenatal stress epigenetically programs dysmasculinization in second-generation offspring via the paternal lineage, Morgan CP, Bale TL. J Neurosci. 2011 Aug 17;31(33):11748-55. doi: 10.1523/JNEUROSCI.1887-11.2011.
Sex differences in prenatal epigenetic programming of stress pathways, Bale TL. Stress. 2011 Jul;14(4):348-56. doi: 10.3109/10253890.2011.586447. Review.
Dr. Swan
Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, Mao CS, Redmon JB, Ternand CL, Sullivan S, Teague JL, and the Study for Future Families Research Team. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect, 2005. 113:1056–1061. PMCID:PMC1280349
Swan SH. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environ Res, 2008. 108(2): 177-84. PMCID: PMC2775531
Arbuckle TE, Hauser R, Swan SH, Mao CS, Longnecker MP, Main KM, Whyatt RM, Mendola P, Legrand M, Rovet J, Till C, Wade M, Jarrell J, Matthews S, Van Vliet G, Bornehag CG, Mieusset R. Meeting report: Measuring endocrine-sensitive endpoints within the first years of life. Environ Health Perspect. 2008 Jul;116(7):948-51. doi: 10.1289/ehp.11226. PMID: 18629319 [PubMed - indexed for MEDLINE] Free PMC Article
Dr. Barrett
Prenatal exposure to stressful life events is associated with masculinized anogenital distance (AGD) in female infants, Barrett ES, Parlett LE, Sathyanarayana S, Liu F, Redmon JB, Wang C, Swan SH. Physiol Behav. 2013 Mar 13;114-115C:14-20. doi: 10.1016/j.physbeh.2013.03.004.
Additional Resources
Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood.
Hompes T, Izzi B, Gellens E, Morreels M, Fieuws S, Pexsters A, Schops G, Dom M, Van Bree R, Freson K, Verhaeghe J, Spitz B, Demyttenaere K, Glover V, Van den Bergh B, Allegaert K, Claes S. J Psychiatr Res. 2013 Apr 5. doi:pii: S0022-3956(13)00092-7. 10.1016/j.jpsychires.2013.03.009.
Evidence for interplay between genes and maternal stress in utero: Monoamine Oxidase A polymorphism moderates effects of life events during pregnancy on infant negative emotionality at 5 weeks. Hill J, Breen G, Quinn J, Tibu F, Sharp H, Pickles A. Genes Brain Behav. 2013 Mar 8. doi: 10.1111/gbb.12033.
Maternal exercise during pregnancy ameliorates the postnatal neuronal impairments induced by prenatal restraint stress in mice. Bustamante C, Henríquez R, Medina F, Reinoso C, Vargas R, Pascual R. Int J Dev Neurosci. 2013 Mar 4;31(4):267-273.
Prenatal stress and affective disorders in a population birth cohort. Kleinhaus K, Harlap S, Perrin M, Manor O, Margalit-Calderon R, Opler M, Friedlander Y, Malaspina D. Bipolar Disord. 2013 Feb;15(1):92-9. doi: 10.1111/bdi.12015.
Prenatal maternal restraint stress exposure alters the reproductive hormone profile and testis development of the rat male offspring. Pallarés ME, Adrover E, Baier CJ, Bourguignon NS, Monteleone MC, Brocco MA, González-Calvar SI, Antonelli MC. Stress. 2013 Feb 7.
High maternal choline intake may prevent the development of stress-related disorders through epigenetic mechanisms. Wilkinson J. Epigenomics. 2012 Oct;4(5):479-80. No abstract available.
AGD: Developmental fluoxetine exposure and prenatal stress alter sexual differentiation of the brain and reproductive behavior in male rat offspring. Rayen I, Steinbusch HW, Charlier TD, Pawluski JL. Psychoneuroendocrinology. 2013 Feb 8. doi:pii: S0306-4530(13)00012-7. 10.1016/j.psyneuen.2013.01.007.
CME: Stress: Pregnancy considerations. Cardwell MS. Obstet Gynecol Surv. 2013 Feb;68(2):119-29. doi: 10.1097/OGX.0b013e31827f2481.
Stress during pregnancy has long been considered detrimental to the developing fetus. New data support the idea that psychosocial stress in utero affects fetal development. This call examined current research on prenatal stress in relation to neurodevelopment and reproductive development, discussed how stress may alter endocrine function and presented data from recent studies that illustrate these concepts.
Dr. Tracy Bale provided a brief overview of the literature on maternal stress and neurodevelopment of offspring in rodent models. Her most recent study uses a genome-wide array approach to screen placental tissue for gene candidates that are sex-biased and stress-responsive in mice, in order to translate the information to humans. Dr. Bale described study results identifying the OGT gene as a promising placental biomarker of maternal stress exposure that may relate to sex-biased outcomes in neurodevelopment.
Dr. Shanna Swan has done extensive research on a measurement of male reproductive development: anogenital distance (AGD). Changes in this physiological measurement have previously been associated with exposure to phthalates and other endocrine disruptors. Dr. Swan is the senior author, and Dr. Emily Barrett the primary author, of a new study entitled Prenatal exposure to stressful life events is associated with masculinized anogenital distance (AGD) in female infants. The co-authors discussed the findings from their study and implications for considering stress as an endocrine disruptor.
Featured Speakers
Tracy Bale, PhD, is an associate professor of neuroscience in the Department of Animal Biology and Psychiatry, and the director of the Neuroscience Center at the University of Pennsylvania. Her research focuses on developing mouse models of increased stress sensitivity related to sex-biased neurodevelopmental and neuropsychiatric diseases. Because women present with affective disorders at more than twice the rate of men, Dr. Bale’s research aims at defining sex differences in stress pathway development and maturation. Studies within Dr. Bale’s lab investigate the timing and sex specificity of early-life events promoting disease susceptibility, the maturation of central stress pathways during key periods of development, and the epigenetic mechanisms involved in long-term effects following stress exposure.
Shanna Swan, PhD, is the vice chair for research in the Department of Preventive Medicine at the Icahn School of Medicine at Mount Sinai. Dr. Swan previously served as professor in the Department of Obstetrics and Gynecology, professor in Environmental Medicine, and director of the Center for Reproductive Epidemiology at the University of Rochester School of Medicine and Dentistry. Since 1998, Dr. Swan has served as principal investigator of the Study for Future Families, a multicenter pregnancy cohort study that examines the environmental causes of geographic variation in reproductive health endpoints. Dr. Swan has published over 150 papers on the impact of environmental exposures on male and female reproductive health.
Emily Barrett, PhD, is an assistant professor in the Department of Obstetrics and Gynecology at the University of Rochester Medical Center, School of Medicine and Dentistry. A trained biological anthropologist and scholar in the University of Rochester’s Women’s Health and the Environment over the Entire Lifespan (WHEEL) program, Dr. Barrett’s research focuses on how ecological factors, including prenatal environment, contribute to variation in reproductive function. Dr. Barrett recently expanded her work to examine how prenatal exposure to environmental chemicals and stress can shape subsequent sexually dimorphic reproductive development.
