Independent and Combined Effects of Prenatal Alcohol Exposure and Prenatal Stress on Fetal HPA Axis Development

• Published in: International journal of molecular sciences Vol. 25; no. 5; p. 2690
• Main Authors: Bakhireva, Ludmila N, Solomon, Elizabeth, Roberts, Melissa H, Ma, Xingya, Rai, Rajani, Wiesel, Alexandria, Jacobson, Sandra W, Weinberg, Joanne, Milligan, Erin D
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26-02-2024; MDPI
• Subjects: 11-beta-Hydroxysteroid Dehydrogenase Type 2; Analysis; Biomarkers - metabolism; Brain; Cortisone; Drinking of alcoholic beverages; Female; Fetal alcohol syndrome; Fetal Development; Fetal Diseases; fetal programming; Fetuses; Gene expression; Genes; Gestational age; Homeostasis; Hormones; HPA axis; Humans; Hypothalamo-Hypophyseal System - metabolism; Pituitary-Adrenal System - metabolism; Placenta; Placenta - metabolism; Pregnancy; Pregnant women; prenatal alcohol; Prenatal Exposure Delayed Effects - metabolism; Protein expression; Proteins; Psychological Tests; Self Report; Stress; Stress, Psychological - metabolism; Umbilical cord; United States > US; stress; placenta; HPA axis; fetal programming; prenatal alcohol; pregnancy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25052690

Prenatal alcohol exposure (PAE) and prenatal stress (PS) are highly prevalent conditions known to affect fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis. The objectives of this study were to assess the effect of light PAE, PS, and PAE-PS interaction on fetal HPA axis activity assessed via placental and umbilical cord blood biomarkers. Participants of the ENRICH-2 cohort were recruited during the second trimester and classified into the PAE and unexposed control groups. PS was assessed by the Perceived Stress Scale. Placental tissue was collected promptly after delivery; gene and protein analysis for 11
-HSD1, 11
-HSD2, and pCRH were conducted by qPCR and ELISA, respectively. Umbilical cord blood was analyzed for cortisone and cortisol. Pearson correlation and multivariable linear regression examined the association of PAE and PS with HPA axis biomarkers. Mean alcohol consumption in the PAE group was ~2 drinks/week. Higher PS was observed in the PAE group (
< 0.01). In multivariable modeling, PS was associated with pCRH gene expression (
= 0.006,
< 0.01), while PAE was associated with 11
-HSD2 protein expression (
= 0.56,
< 0.01). A significant alcohol-by-stress interaction was observed with respect to 11
-HSD2 protein expression (
< 0.01). Results indicate that PAE and PS may independently and in combination affect fetal programming of the HPA axis.