{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T04:11:02Z","timestamp":1782706262014,"version":"3.54.5"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2017,9,11]],"date-time":"2017-09-11T00:00:00Z","timestamp":1505088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>A long standing axiom in the field of teratology states that the teratogenic period, when most birth defects are produced, occurs during the third to eighth weeks of development post-fertilization. Any insults prior to this time are thought to result in a slowing of embryonic growth from which the conceptus recovers or death of the embryo followed by spontaneous abortion. However, new insights into embryonic development during the first two weeks, including formation of the anterior-posterior, dorsal-ventral, and left-right axes, suggests that signaling pathways regulating these processes are prime targets for genetic and toxic insults. Establishment of the left-right (laterality) axis is particularly sensitive to disruption at very early stages of development and these perturbations result in a wide variety of congenital malformations, especially heart defects. Thus, the time for teratogenic insults resulting in birth defects should be reset to include the first two weeks of development.<\/jats:p>","DOI":"10.3390\/jcdd4030015","type":"journal-article","created":{"date-parts":[[2017,9,11]],"date-time":"2017-09-11T10:28:46Z","timestamp":1505125726000},"page":"15","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Establishing the Embryonic Axes: Prime Time for Teratogenic Insults"],"prefix":"10.3390","volume":"4","author":[{"given":"Thomas","family":"Sadler","sequence":"first","affiliation":[{"name":"Senior Fellow, Greenwood Genetics Center, Greenwood, SC 29646, USA"},{"name":"Department of Pediatrics, University of Utah, Salt Lake City, UT 84108, USA"},{"name":"Department of Anatomy, Quillen College of Medicine, East Tennessee State University, Johnson, TN 37614, USA"},{"name":"78 Lemon Gulch Lane, Sheridan, MT 59749, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,9,11]]},"reference":[{"key":"ref_1","first-page":"47","article-title":"Current status of teratology: General principles and mechanisms derived from animal studies","volume":"Volume 1","author":"Wilson","year":"1977","journal-title":"Handbook of Teratology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.devcel.2006.02.017","article-title":"The mouse embryo autonomously acquires anterior-posterior polarity at implantation","volume":"10","author":"Takaoka","year":"2006","journal-title":"Dev. 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