D'Errico J N, Fournier S B, Stapleton P A
Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, 160 Frelinghuysen Rd., Piscataway, NJ 08854, USA.
Environmental and Occupational Health Sciences Institute, 170 Frelinghuysen Rd., Piscataway, NJ 08854, USA.
Front Toxicol. 2021 Mar;3. doi: 10.3389/ftox.2021.643804. Epub 2021 Mar 23.
Fetal growth restriction (FGR) is a condition with several underlying etiologies including gestational disease (e.g., preeclampsia, gestational diabetes) and xenobiotic exposure (e.g., environmental contaminants, pharmaceuticals, recreational drugs). Rodent models allow study of FGR pathogenesis. However, given the multiparous rodent pregnancy, fetal growth variability within uterine horns may arise. To ascertain whether intrauterine position is a determinant of fetal growth, we redesigned fetal weight analysis to include litter size and maternal weight. Our FGR model is produced by exposing pregnant Sprague Dawley rats to aerosolized titanium dioxide nanoparticles at 9.44 ± 0.26 mg/m on gestational day (GD) 4, GD 12 or GD 17 or 9.53 ± 1.01 mg/m between GD 4-GD 19. In this study fetal weight data was reorganized by intrauterine location [i.e., right/left uterine horn and ovarian/middle/vaginal position] and normalized by maternal weight and number of feti per uterine horn. A significant difference in fetal weight in the middle location in controls (0.061g ± 0.001 vs. 0.055g ± 0.002), GD 4 (0.033g ± 0.003 vs. 0.049g ± 0.004), and GD 17 (0.047g ± 0.002 vs. 0.038g ± 0.002) exposed animals was identified. Additionally, GD 4 exposure produced significantly smaller feti in the right uterine horn at the ovarian end (0.052g ± 0.003 vs. 0.029g ± 0.003) and middle of the right uterine horn (0.060g ± 0.001 vs. 0.033g ± 0.003). GD 17 exposure produced significantly smaller feti in the left uterine horn middle location (0.055g ± 0.002 vs. 0.033 ± 0.002). Placental weights were unaffected, and placental efficiency was reduced in the right uterine horn middle location after GD 17 exposure (5.74g ± 0.16 vs. 5.09g ± 0.14). These findings identified: 1) differences in fetal weight of controls between the right and left horns in the middle position, and 2) differential effects of single whole-body pulmonary exposure to titanium dioxide nanoparticles on fetal weight by position and window of maternal exposure. In conclusion, these results indicate that consideration for intrauterine position, maternal weight, and number of feti per horn provides a more sensitive assessment of FGR from rodent reproductive and developmental studies.
胎儿生长受限（FGR）是一种由多种潜在病因引起的病症，包括妊娠疾病（如先兆子痫、妊娠糖尿病）和外源性物质暴露（如环境污染物、药物、消遣性毒品）。啮齿动物模型有助于研究FGR的发病机制。然而，鉴于啮齿动物多胎妊娠，子宫角内的胎儿生长可能会出现差异。为了确定子宫内位置是否是胎儿生长的决定因素，我们重新设计了胎儿体重分析，将窝仔数和母体体重纳入其中。我们的FGR模型是通过在妊娠第4天、第12天或第17天，让怀孕的斯普拉格·道利大鼠暴露于浓度为9.44±0.26毫克/立方米的雾化二氧化钛纳米颗粒中，或在妊娠第4天至第19天暴露于浓度为9.53±1.01毫克/立方米的雾化二氧化钛纳米颗粒中产生的。在本研究中，胎儿体重数据按子宫内位置[即右/左子宫角和卵巢/中间/阴道位置]进行了重新整理，并通过母体体重和每个子宫角内的胎儿数量进行了标准化。在对照组的中间位置（0.061克±0.001对0.055克±0.002）、妊娠第4天（0.033克±0.003对0.049克±
