Embryo developmental disruption during organogenesis produced by CF‐1 murine periconceptional alcohol consumption

Abstract

The aim was to study the control females (CF)-1 mouse embryo differentiation, growth, morphology on embryonic E- and N-cadherin expression at midgestation after periconceptional moderate alcohol ingestion. Adult female mice were exposed to 10% ethanol in drinking water for 17 days previous to and up to day 10 of gestation (ethanol-exposed females, EF) and were compared with nonexposed CF. EF presented reduced quantities of E10 to E10.5 embryos, greater percentage of embryos at stages less than E7.5, reduced implantation site numbers/female, and increased resorptions compared with CF. EF-embryo growth was significantly affected as evidenced by reduced cephalic and body sizes of E10 and E10.5 embryos (scanning electron microscopy) and decreased protein content of E10.5 embryos vs. CF embryos. A significantly higher percentage of EF-E10-10.5 embryos presented abnormal neural tube (NT) closure vs. the percentage of CF. E10 embryos from EF presented elevated tissue disorganization, pyknosis and nuclear condensation in somites, mesenchymal and neuroepithelial tissue. Immunohistochemical E- and N-cadherin distribution patterns were similar in organic structures of E10 embryos between groups. However, western blot revealed that E- and N-cadherin expression levels were significantly increased in EF-derived embryos vs. controls. Perigestational ethanol consumption by CF-1 mice induced significant damage in the organogenic embryogenesis by producing delayed differentiation, growth deficiencies, and increasing the frequency of NT defects. Ethanol exposure may disrupt cell-cell adhesion leading to upregulation of E- and N-cadherin expression suggesting that deregulation of cell adhesion molecules could be involved in the disruption of embryo development at organogenesis in CF-1 mouse.

Metabolic effects following periconceptional alcohol exposure in rat adult offspring: modulations by a postnatal western diet

“…This was later replicated with similar results in a mouse in vivo study (Cebral et al, 2000). When extending these experiments further, the research group showed that EtOH-exposed female mice had fewer embryos on E10, reduced implantation site numbers, increased resorption, delayed embryonic development and abnormal neural tube closure (Coll et al, 2011). In this study however, the PC period was defined as 17 days prior to conception until E10 (Coll et al, 2011), which is after embryonic implantation in mice.…”

“…When extending these experiments further, the research group showed that EtOH-exposed female mice had fewer embryos on E10, reduced implantation site numbers, increased resorption, delayed embryonic development and abnormal neural tube closure (Coll et al, 2011). In this study however, the PC period was defined as 17 days prior to conception until E10 (Coll et al, 2011), which is after embryonic implantation in mice.Collectively, these studies confirm that the early embryo is affected by EtOH, yet no one has investigated the long term consequences of PC alcohol. …”

Oxidative stress and cellular and tissue damage in organogenic outbred mouse embryos after moderate perigestational alcohol intake

“…The major morphological phenotypes observed in embryos from ethanol‐treated females were open or abnormally closed neural tube or mal‐rotated embryos. The percentage of abnormal E10 embryos significantly increased in the ethanol‐treated group compared to controls (control, 9.5%; ethanol‐treated, 36.0% of abnormal E10 embryos over the total number of implantation sites [ p < 0.001]) (Coll et al, ).…”

“…Studies in different animals suggested that ethanol as well as acetaldehyde, the primary oxidative metabolite of ethanol produced in vivo during placental detoxification (Brocardo et al, ), can lead to altered fetal development and growth (Bosco & Diaz, ). We previously demonstrated that maternal perigestational 10% ethanol administration up to Day 10 of gestation produced neural tube closure defects, altered embryonic tissues, and led to deficient cell adhesion with up‐regulated cadherin expression (Coll et al, ), increased production of embryo Prostaglandin E (Cebral et al, ), and deregulated prostaglandin‐nitric oxide pathways in organogenic E10 embryos. The present study demonstrated, for the first time, that short‐term, moderate ethanol intake before pregnancy and continuing up to early organogenesis in embryos—which produced low blood‐alcohol levels in an outbred mouse model—induced moderate oxidative stress in organogenic, E10 embryos, leading to deleterious oxidative stress‐related cellular and molecular effects in different organs and tissues of the ethanol‐exposed embryos.…”

Adverse prenatal environment and kidney development: implications for programing of adult disease

“…Other clinically relevant perturbations include periconceptional alcohol exposure that resulted in changes in E-and N-cadherin expression and slowed development of embryos (Coll et al 2011). Periconceptional alcohol exposure has also been shown to impair placental development that may contribute to fetal growth restriction (Gardebjer et al 2014).…”