Abstract
BackgroundIn recent decades, there has been a growing interest in the impact of insults during pregnancy on postnatal health and disease. It is known that changes in placental development can impact fetal growth and subsequent susceptibility to adult onset diseases; however, a method to collect sufficient placental tissues for both histological and gene expression analyses during gestation without compromising the pregnancy has not been described. The ewe is an established biomedical model for the study of fetal development. Due to its cotyledonary placental type, the sheep has potential for surgical removal of materno-fetal exchange tissues, i.e., placentomes. A novel surgical procedure was developed in well-fed control ewes to excise a single placentome at mid-gestation.ResultsA follow-up study was performed in a cohort of nutrient-restricted ewes to investigate rapid placental changes in response to undernutrition. The surgery averaged 19 min, and there were no viability differences between control and sham ewes. Nutrient restricted fetuses were smaller than controls (4.7 ± 0.1 kg vs. 5.6 ± 0.2 kg; P < 0.05), with greater dam weight loss (− 32.4 ± 1.3 kg vs. 14.2 ± 2.2 kg; P < 0.01), and smaller placentomes at necropsy (5.7 ± 0.3 g vs. 7.2 ± 0.9 g; P < 0.05). Weight of sampled placentomes and placentome numbers did not differ.ConclusionsWith this technique, gestational studies in the sheep model will provide insight into the onset and complexity of changes in gene expression in placentomes resulting from undernutrition (as described in our study), overnutrition, alcohol or substance abuse, and environmental or disease factors of relevance and concern regarding the reproductive health and developmental origins of health and disease in humans and in animals.
Highlights
For the past half century, researchers have performed terminal procedures on ruminants to investigate placentome development and its impacts on fetal growth and health [1]
The ewe has been hailed as a valuable research model for studies relevant to human pregnancy [7, 8]; knowledge of placental/fetal interactions and how treatments or diseases impact them is critical for understanding, diagnosing, and preventing, causes and effects of deleterious events in placental development which occurs during early- to mid-gestation
Many of the described experimental insults produce spectral phenotypes, which can perhaps best be understood by retrospectively comparing the phenotype to the conditions that existed during early stages of fetal-placental development and before the phenotype of the live offspring is established
Summary
For the past half century, researchers have performed terminal procedures on ruminants to investigate placentome development and its impacts on fetal growth and health [1]. The ewe has been hailed as a valuable research model for studies relevant to human pregnancy [7, 8]; knowledge of placental/fetal interactions and how treatments or diseases impact them is critical for understanding, diagnosing, and preventing, causes and effects of deleterious events in placental development which occurs during early- to mid-gestation. A non-terminal surgical technique that allows for sampling of placentomes from a pregnant ewe would provide critical knowledge related to gene-environmental interactions affecting fetal-placental development during gestation and how those interactions impact lifelong health of that offspring. It is known that changes in placental development can impact fetal growth and subsequent susceptibility to adult onset diseases; a method to collect sufficient placental tissues for both histological and gene expression analyses during gestation without compromising the pregnancy has not been described. A novel surgical procedure was developed in well-fed control ewes to excise a single placentome at mid-gestation
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