Taube Nicole, Kabir Raihan, Ebenebe Obialunanma V, Garbus Haley, Din Sarah-Marie Alam El, Illingworth Emily, Fitch Michael, Wang Nadan, Kohr Mark J
bioRxiv. 2023 Sep 29:2023.09.28.559986. doi: 10.1101/2023.09.28.559986.
Exposure to inorganic arsenic through drinking water is widespread and has been linked to many chronic diseases, including cardiovascular disease. Arsenic exposure has been shown to alter hypertrophic signaling in the adult heart, as well as in-utero offspring development. However, the effect of arsenic on maternal cardiac remodeling during pregnancy has not been studied. As such, there is a need to understand how environmental exposure contributes to adverse pregnancy-related cardiovascular events. This study seeks to understand the impact of trivalent inorganic arsenic exposure during gestation on maternal cardiac remodeling in late pregnancy, as well as offspring outcomes. C57BL/6J mice were exposed to 0 (control), 100 or 1000 µg/L sodium arsenite (NaAsO ) beginning at embryonic day (E) 2.5 and continuing through E17.5. Maternal heart function and size were assessed via transthoracic echocardiography, gravimetric measurement, and histology. Transcript levels of hypertrophic markers were probed via qRT-PCR and confirmed by western blot. Offspring outcomes were assessed through echocardiography and gravimetric measurement. We found that exposure to 1000 µg/L iAs abrogated normal physiologic growth of the maternal heart during late pregnancy and reduced transcript levels of estrogen receptor alpha (ERα), progesterone receptor membrane component 1 (Pgrmc1) and progesterone receptor membrane component 2 (Pgrmc2). Both 100 and 1000 µg/L iAs also reduced transcription of protein kinase B (Akt) and atrial natriuretic peptide (ANP). Akt protein expression was also significantly reduced after 1000 µg/L iAs exposure in the maternal heart with no change in activating phosphorylation. This significant abrogation of maternal cardiac hypertrophy suggests that arsenic exposure during pregnancy can potentially contribute to cardiovascular disease. Taken together, our findings further underscore the importance of reducing arsenic exposure during pregnancy and indicate that more research is needed to assess the impact of arsenic and other environmental exposures on the maternal heart and adverse pregnancy events.
通过饮用水接触无机砷的情况很普遍，并且与包括心血管疾病在内的许多慢性疾病有关。已表明砷暴露会改变成年心脏以及子宫内子代发育中的肥厚信号传导。然而，砷对孕期母体心脏重塑的影响尚未得到研究。因此，有必要了解环境暴露如何导致与妊娠相关的不良心血管事件。本研究旨在了解妊娠期三价无机砷暴露对妊娠晚期母体心脏重塑以及子代结局的影响。从胚胎第2.5天开始，将C57BL/6J小鼠暴露于0（对照）、100或1000μg/L的亚砷酸钠（NaAsO₂）中，并持续至胚胎第17.5天。通过经胸超声心动图、重量测量和组织学评估母体心脏功能和大小。通过qRT-PCR检测肥厚标志物的转录水平，并通过蛋白质印迹法进行确认。通过超声心动图和重量测量评估子代结局。我们发现，暴露于1000μg/L的无机砷会消除妊娠晚期母体心脏的正常生理生长，并降低雌激素受体α（ERα）、孕激素受体膜成分1（Pgrmc1）和孕激素受体膜成分（Pgrmc2）的转录水平。100和1000μg/L的无机砷还会降低蛋白激酶B（Akt）和心钠素（ANP）的转录。在母体心脏中暴露于1000μg/L的无机砷后，Akt蛋白表达也显著降低，而激活磷酸化没有变化。母体心脏肥大的这种显著消除表明，孕期砷暴露可能会导致心血管疾病。综上所述，我们的研究结果进一步强调了孕期减少砷暴露的重要性，并表明需要更多研究来评估砷和其他环境暴露对母体心脏和不良妊娠事件的影响。
