Crew Rachael C, Mark Peter J, Clarke Michael W, Waddell Brendan J
School of Anatomy, Physiology & Human Biology, The University of Western Australia, Perth, Western Australia, Australia.
Metabolomics Australia, The University of Western Australia, Perth, Western Australia, Australia.
Biol Reprod. 2016 Sep;95(3):55. doi: 10.1095/biolreprod.116.139451. Epub 2016 Jul 27.
Maternal obesity increases the risk of abnormal fetal growth, but the underlying mechanisms remain unclear. Because steroid hormones regulate fetal growth, and both pregnancy and obesity markedly alter circadian biology, we hypothesized that maternal obesity disrupts the normal rhythmic profiles of steroid hormones in rat pregnancy. Obesity was established by cafeteria (CAF) feeding for 8 wk prior to mating and throughout pregnancy. Control (CON) animals had ad libitum access to chow. Daily profiles of plasma corticosterone, 11-dehydrocorticosterone, progesterone, and testosterone were measured at Days 15 and 21 of gestation (term = 23 days) in maternal (both days) and fetal (Day 21) plasma. CAF mothers exhibited increased adiposity relative to CON and showed fetal and placental growth restriction. There was no change, however, in total fetal or placental mass due to slightly larger litter sizes in CAF. Nocturnal declines in progesterone were observed in maternal (39% lower) and fetal (45% lower) plasma in CON animals, but these were absent in CAF animals. CAF mothers were hyperlipidemic at both days of gestation, but this effect was isolated to the dark period at Day 21. CAF maternal testosterone was slightly lower at Day 15 (8%) but increased above CON by Day 21 (16%). Despite elevated maternal testosterone, male fetal testosterone was suppressed by obesity on Day 21. Neither maternal nor fetal glucocorticoid profiles were affected by obesity. In conclusion, obesity disrupts rhythmic profiles of maternal and fetal progesterone, preventing the normal nocturnal decline. Obesity subtly changed testosterone profiles but did not alter maternal and fetal glucocorticoids.
母亲肥胖会增加胎儿生长异常的风险，但其潜在机制尚不清楚。由于类固醇激素调节胎儿生长，且妊娠和肥胖都会显著改变昼夜节律生物学，我们推测母亲肥胖会扰乱大鼠妊娠期间类固醇激素的正常节律模式。在交配前8周及整个妊娠期，通过自由采食高热量食物（CAF）建立肥胖模型。对照（CON）组动物可自由进食普通饲料。在妊娠第15天和第21天（足月为23天），分别测定母体（两天均测）和胎儿（第21天测）血浆中皮质酮、11 - 脱氢皮质酮、孕酮和睾酮的每日变化情况。与CON组相比，CAF组母亲的肥胖程度增加，且出现胎儿和胎盘生长受限。然而，由于CAF组产仔数略多，胎儿或胎盘的总质量没有变化。在CON组动物的母体（降低39%）和胎儿（降低45%）血浆中观察到孕酮的夜间下降，但CAF组动物中未出现这种情况。CAF组母亲在妊娠的两天均出现高脂血症，但这种影响在第21天仅限于黑暗期。CAF组母体睾酮在第15天略低（8%），但到第21天高于CON组（16%）。尽管母体睾酮升高，但肥胖在第21天抑制了雄性胎儿的睾酮。肥胖对母体和胎儿的糖皮质激素水平均无影响。总之，肥胖扰乱了母体和胎儿孕酮的节律模式，阻止了正常的夜间下降。肥胖轻微改变了睾酮水平，但未改变母体和胎儿的糖皮质激素水平。
