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Half to two\u2010thirds of embryos are lost, and environmental and genetic causes are nearly equal. Simply put, it can be inferred that this is a difficult period for normal embryos, but that environmental stresses may cause homeostatic responses that move from adaptive to maladaptive with increasing exposures. At the lower 50% estimate, miscarriage causes greater loss\u2010of\u2010life than all cancers combined or of all cardio\u2010 and cerebral\u2010vascular accidents combined. Surprisingly, we do not know if miscarriage rates are increasing or decreasing. Overshadowed by the magnitude of miscarriages, are insufficient data on teratogenic or epigenetic imbalances in surviving embryos and their stem cells. Superimposed on the difficult normal trajectory for peri\u2010gastrulation embryos are added malnutrition, hormonal, and environmental stresses. An overarching hypothesis is that high throughput screens (HTS) using cultured viable reporter embryonic and placental stem cells (e.g., embryonic stem cells [ESC] and trophoblast stem cells [TSC] that report status using fluorescent reporters in living cells) from the pre\u2010gastrulation embryo will most rapidly test a range of hormonal, environmental, nutritional, drug, and diet supplement stresses that decrease stem cell proliferation and imbalance stemness\/differentiation. A second hypothesis is that TSC respond with greater sensitivity in magnitude to stress that would cause miscarriage, but ESC are stress\u2010resistant to irreversible stemness loss and are best used to predict long\u2010term health defects. DevTox testing needs more ESC and TSC HTS to model environmental stresses leading to miscarriage or teratogenesis and more research on epidemiology of stress and miscarriage. This endeavor also requires a shift in emphasis on pre\u2010 and early gastrulation events during the difficult period of maximum loss by miscarriage.<\/jats:p>","DOI":"10.1002\/bdr2.2079","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T07:18:22Z","timestamp":1660807102000},"page":"1014-1036","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Using high throughput screens to predict miscarriages with placental stem cells and long\u2010term stress effects with embryonic stem cells"],"prefix":"10.1002","volume":"114","author":[{"given":"Elizabeth E.","family":"Puscheck","sequence":"first","affiliation":[{"name":"CS Mott Center for Human Growth and Development, Department of Ob\/Gyn, Reproductive Endocrinology and Infertility Wayne State University School of Medicine Detroit Michigan USA"},{"name":"Reproductive Stress 3M Inc Grosse Pointe Farms Michigan USA"},{"name":"Invia Fertility Clinics Hoffman Estates Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximena","family":"Ruden","sequence":"additional","affiliation":[{"name":"CS Mott Center for Human Growth and Development, Department of Ob\/Gyn, Reproductive Endocrinology and Infertility Wayne State University School of Medicine Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Singh","sequence":"additional","affiliation":[{"name":"CS Mott Center for Human Growth and Development, Department of Ob\/Gyn, Reproductive Endocrinology and Infertility Wayne State University School of Medicine Detroit Michigan USA"},{"name":"Center for Molecular Medicine and Genetics Wayne State University School of Medicine Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Abdulhasan","sequence":"additional","affiliation":[{"name":"CS Mott Center for Human Growth and Development, Department of Ob\/Gyn, Reproductive Endocrinology and Infertility Wayne State University School of Medicine Detroit Michigan USA"},{"name":"Reproductive Stress 3M Inc Grosse Pointe Farms Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas M.","family":"Ruden","sequence":"additional","affiliation":[{"name":"CS Mott Center for Human Growth and Development, Department of Ob\/Gyn, Reproductive Endocrinology and Infertility Wayne State University School of Medicine Detroit Michigan USA"},{"name":"Invia Fertility Clinics Hoffman Estates Illinois USA"},{"name":"Institute for Environmental Health Science Wayne State University School of Medicine Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awoniyi O.","family":"Awonuga","sequence":"additional","affiliation":[{"name":"CS Mott Center for Human Growth and Development, Department of Ob\/Gyn, Reproductive Endocrinology and Infertility Wayne State University School of Medicine Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Rappolee","sequence":"additional","affiliation":[{"name":"CS Mott Center for Human Growth and Development, Department of Ob\/Gyn, Reproductive Endocrinology and Infertility Wayne State University School of Medicine Detroit Michigan USA"},{"name":"Reproductive Stress 3M Inc Grosse Pointe Farms Michigan USA"},{"name":"Invia Fertility Clinics Hoffman Estates Illinois USA"},{"name":"Institute for Environmental Health Science Wayne State University School of Medicine Detroit Michigan USA"},{"name":"Program for Reproductive Sciences and Department of Physiology Wayne State University School of Medicine Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,18]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2021.0330"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/ftox.2021.709747"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406185101"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02743"},{"key":"e_1_2_16_6_1","volume-title":"Molecular biology of the cell","author":"Alberts B.","year":"2015"},{"key":"e_1_2_16_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.12.004"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2966"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-014-1630-3"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.050864"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.21342"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811841106"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2006.07.005"},{"key":"e_1_2_16_14_1","volume-title":"Teratology primer","author":"Bleyl S. 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