Rehan Virender K, Li Yishi, Corral Julia, Saraswat Aditi, Husain Sumair, Dhar Ankita, Sakurai Reiko, Khorram Omid, Torday John S
1Departments of Pediatrics and Obstetrics and Gynecology, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
Reprod Sci. 2014 Apr;21(4):517-25. doi: 10.1177/1933719113503404. Epub 2013 Sep 10.
Maternal food restriction (MFR) during pregnancy affects pulmonary surfactant production in the intrauterine growth-restricted (IUGR) offspring through unknown mechanisms. Since pulmonary surfactant production is regulated by maternal and fetal corticosteroid levels, both known to be increased in IUGR pregnancies, we hypothesized that metyrapone (MTP), a glucocorticoid synthesis inhibitor, would block the effects of MFR on surfactant production in the offspring. Three groups of pregnant rat dams were used (1) control dams fed ad libitum; (2) MFR (50% reduction in calories) from days 10 to 22 of gestation; and (3) MFR + MTP in drinking water (0.5 mg/mL), days 11 to 22 of gestation. At 5 months, the MFR offspring weighed significantly more, had reduced alveolar number, increased septal thickness, and decreased surfactant protein and phospholipid synthesis. These MFR-induced effects were normalized by the antiglucocorticoid MTP, suggesting that the stress of MFR causes hypercorticoidism, altering lung structure and function in adulthood.
孕期母体食物限制（MFR）会通过未知机制影响宫内生长受限（IUGR）子代的肺表面活性物质生成。由于肺表面活性物质的生成受母体和胎儿皮质类固醇水平调控，而这两者在IUGR妊娠中均已知会升高，我们推测甲吡酮（MTP），一种糖皮质激素合成抑制剂，会阻断MFR对后代肺表面活性物质生成的影响。使用了三组怀孕大鼠母鼠：（1）自由采食的对照母鼠；（2）在妊娠第10天至22天进行MFR（热量减少50%）；（3）在妊娠第11天至22天，在饮水中添加MTP（0.5毫克/毫升）的MFR母鼠。在5个月时，MFR子代体重显著更重，肺泡数量减少，间隔厚度增加，肺表面活性物质蛋白和磷脂合成减少。这些MFR诱导的效应通过抗糖皮质激素MTP恢复正常，表明MFR的应激导致皮质醇增多症，改变成年期的肺结构和功能。
