{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T16:08:37Z","timestamp":1768666117107,"version":"3.49.0"},"reference-count":106,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T00:00:00Z","timestamp":1708905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health National Institute on Alcohol Abuse and Alcoholism","award":["2R01AA021771"],"award-info":[{"award-number":["2R01AA021771"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u03b2-HSD1, 11\u03b2-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 (p &lt; 0.01). In multivariable modeling, PS was associated with pCRH gene expression (\u03b2 = 0.006, p &lt; 0.01), while PAE was associated with 11\u03b2-HSD2 protein expression (\u03b2 = 0.56, p &lt; 0.01). A significant alcohol-by-stress interaction was observed with respect to 11\u03b2-HSD2 protein expression (p &lt; 0.01). Results indicate that PAE and PS may independently and in combination affect fetal programming of the HPA axis.<\/jats:p>","DOI":"10.3390\/ijms25052690","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T07:51:39Z","timestamp":1708933899000},"page":"2690","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Independent and Combined Effects of Prenatal Alcohol Exposure and Prenatal Stress on Fetal HPA Axis Development"],"prefix":"10.3390","volume":"25","author":[{"given":"Ludmila N.","family":"Bakhireva","sequence":"first","affiliation":[{"name":"College of Pharmacy Substance Use Research and Education Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Solomon","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM 87106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1314-4906","authenticated-orcid":false,"given":"Melissa H.","family":"Roberts","sequence":"additional","affiliation":[{"name":"College of Pharmacy Substance Use Research and Education Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingya","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Pharmacy Substance Use Research and Education Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajani","family":"Rai","sequence":"additional","affiliation":[{"name":"College of Pharmacy Substance Use Research and Education Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandria","family":"Wiesel","sequence":"additional","affiliation":[{"name":"College of Pharmacy Substance Use Research and Education Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9768-2671","authenticated-orcid":false,"given":"Sandra W.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7937-3904","authenticated-orcid":false,"given":"Joanne","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Cellular and Physiological Sciences, Faculty of Medicine, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin D.","family":"Milligan","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM 87106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s10995-008-0328-2","article-title":"National Birth Defects Prevention Study Alcohol Consumption by Women before and during Pregnancy","volume":"13","author":"Ethen","year":"2009","journal-title":"Matern. 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