Alterations in placental vascular formation in parental alcohol exposure

Introduction: Recent studies indicate that maternal and paternal alcohol use disrupts the formation of placental vasculature. This disruption leads to placental insufficiency and fetal growth restriction, thus negatively affecting long-term offspring health. However, our understanding of the nature of such disruptions in placental vascular development remains limited. Our objective in this study was to understand and quantify the alterations in the collagen network interwinding the vascular bed in the placenta caused by parental alcohol exposure. Methods: The animal study was approved by the Texas A&M University IACUC. All experiments were performed following IACUC guidelines and regulations. 90-day postnatal C57BL/6J mice were used. The mice were separated into four groups: maternal (MatExp), paternal (PatExp), dual parental (DualExp), and control. We exposed males to 10% w/v ethanol six weeks before conception, while we exposed females one week before conception and for the first ten days of pregnancy. We used a 2x2 factorial experimental design to compare the placenta of offspring across groups. We examined placental development (n=35 placenta) on gestational day 16.5 using histological analysis, stained with Picro Sirius Red stain (Control n=5; MatExp n=13; PatExp n=10, DualExp n=7). The collagen portion of the images was isolated and analyzed to determine collagen fiber content and orientation. Statistical analysis was performed using one-way ANOVA with Tukey's correction for multiple comparisons. Significance was accepted at p<0.05. Results: Histological analysis indicated that collagen content decreased significantly in the MatExp and DualExp groups. (control: 59±7.9%; MatExp: 48±7.9% with p=0.0117 vs. control; PatExp: 53.7±9.7%; DualExp: 47.8±5.9% with p=0.0469 vs. control). In addition, collagen fiber spread, defined as the standard deviation in the collagen fiber orientation, increased in the MatExp group, but the change was less notable in the other two groups (control: 12±3.8°; MatExp: 23.6±6.5° with p=0.0826 vs. control; PatExp: 19.3±8.4°; DualExp: 18.9±5.9°). Conclusions: Alcohol-induced disorganization of the connective tissue supporting placental vasculature could indicate a significant disruption in placental blood supply, leading to placental dysfunction. Further investigation is required to elucidate the effects of the disorganized vasculature on placental function. This work was supported by the National Institutes of Health R00HL138288 to R.A. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.