Griffith Julie A, Dunn Allison, DeVallance Evan, Schafner Kallie J, Engles Kevin J, Batchelor Thomas P, Goldsmith William T, Wix Kimberley, Hussain Salik, Bowdridge Elizabeth C, Nurkiewicz Timothy R
Department of Physiology, Pharmacology, and Toxicology, West Virginia University School of Medicine, Morgantown, WV, United States.
Center for Inhalation Toxicology, West Virginia University School of Medicine, Morgantown, WV, United States.
Front Toxicol. 2023 Mar 6;5:1096173. doi: 10.3389/ftox.2023.1096173. eCollection 2023.
The placenta plays a critical role in nutrient-waste exchange between the maternal and fetal circulations, thus functioning as an interface that profoundly impacts fetal growth and development. The placenta has long been considered an asexual organ, but, due to its embryonic origin it shares the same sex as the fetus. Exposures to toxicant such as diesel exhaust, have been shown to result in sexually dimorphic outcomes like decreased placental mass in exposed females. Therefore, we hypothesize that maternal nano-TiO inhalation exposure during gestation alters placental hemodynamics in a sexually dimorphic manner. Pregnant Sprague-Dawley rats were exposed from gestational day 10-19 to nano-TiO aerosols (12.17 ± 1.69 mg/m) or filtered air (sham-control). Dams were euthanized on GD20, and fetal tissue was collected based on fetal sex: whole placentas, placental junctional zone (JZ), and placental labyrinth zone (LZ). Fetal mass, placental mass, and placental zone percent areas were assessed for sex-based differences. Exposed fetal females were significantly smaller compared to their exposed male counterparts (2.65 ± 0.03 g vs 2.78 ± 0.04 g). Nano-TiO exposed fetal females had a significantly decreased percent junctional zone area compared to the sham-control females (24.37 ± 1.30% vs 30.39 ± 1.54%). The percent labyrinth zone area was significantly increased for nano-TiO females compared to sham-control females (75.63 ± 1.30% vs 69.61 ± 1.54%). Placental flow and hemodynamics were assessed with a variety of vasoactive substances. It was found that nano-TiO exposed fetal females only had a significant decrease in outflow pressure in the presence of the thromboxane (TXA) mimetic, U46619, compared to sham-control fetal females (3.97 ± 1.30 mm Hg vs 9.10 ± 1.07 mm Hg) and nano-TiO fetal males (9.96 ± 0.66 mm Hg). Maternal nano-TiO inhalation exposure has a greater effect on fetal female mass, placental zone mass and area, and adversely impacts placental vasoreactivity. This may influence the female growth and development later in life, future studies need to further study the impact of maternal nano-TiO inhalation exposure on zone specific mechanisms.
胎盘在母体和胎儿循环之间的营养物质-废物交换中起着关键作用，因此作为一个对胎儿生长发育有深远影响的界面发挥作用。长期以来，胎盘一直被认为是一个无性别的器官，但由于其胚胎起源，它与胎儿性别相同。已表明接触柴油尾气等有毒物质会导致性别特异性结果，如接触的雌性动物胎盘质量下降。因此，我们假设孕期母体吸入纳米二氧化钛会以性别特异性方式改变胎盘血流动力学。将怀孕的斯普拉格-道利大鼠从妊娠第10天至第19天暴露于纳米二氧化钛气溶胶（12.17±1.69毫克/立方米）或过滤空气（假对照）中。在妊娠第20天对母鼠实施安乐死，并根据胎儿性别收集胎儿组织：整个胎盘、胎盘交界区（JZ）和胎盘迷路区（LZ）。评估胎儿体重、胎盘重量和胎盘区面积百分比的性别差异。与暴露的雄性胎儿相比，暴露的雌性胎儿明显更小（2.65±0.03克对2.78±0.04克）。与假对照雌性相比，暴露于纳米二氧化钛的雌性胎儿交界区面积百分比显著降低（24.37±1.30%对30.39±1.54%）。与假对照雌性相比，纳米二氧化钛暴露的雌性胎儿迷路区面积百分比显著增加（75.63±1.30%对69.61±1.54%）。用多种血管活性物质评估胎盘血流和血流动力学。结果发现，与假对照雌性胎儿（3.97±1.30毫米汞柱对9.10±1.07毫米汞柱）和纳米二氧化钛暴露的雄性胎儿（9.96±0.66毫米汞柱）相比，暴露于纳米二氧化钛的雌性胎儿仅在存在血栓素（TXA）模拟物U46619时流出压力显著降低。孕期母体吸入纳米二氧化钛对雌性胎儿体重、胎盘区质量和面积有更大影响，并对胎盘血管反应性产生不利影响。这可能会影响雌性个体后期的生长发育，未来的研究需要进一步探讨孕期母体吸入纳米二氧化钛对特定区域机制的影响。
