Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
Department of Biological Sciences, Southeastern Louisiana University, Hammond, Louisiana, USA.
Physiol Rep. 2022 Sep;10(17):e15444. doi: 10.14814/phy2.15444.
AbstractPreeclampsia (PE) is a hypertensive disorder that impacts 2-8% of pregnant women worldwide. It is characterized by new onset hypertension during the second half of gestation and is a leading cause of maternal and fetal morbidity/mortality. Maternal obesity increases the risk of PE and is a key predictor of childhood obesity and potentially offspring cardiometabolic complications in a sex-dependent manner. The influence of the maternal obesogenic environment, with superimposed PE, on offspring development into adulthood is unknown. Obese BPH/5 mice spontaneously exhibit late-gestational hypertension, fetal demise and growth restriction, and excessive gestational weight gain. BPH/5 females have improved pregnancy outcomes when maternal weight loss via pair-feeding is imposed beginning at conception. We hypothesized that phenotypic differences between female and male BPH/5 offspring can be influenced by pair feeding BPH/5 dams during pregnancy. BPH/5 pair-fed dams have improved litter sizes and increased fetal body weights. BPH/5 offspring born to ad libitum dams have similar sex ratios, body weights, and fecal microbiome as well as increased blood pressure that is reduced in the dam pair-fed offspring. Both BPH/5 male and female offspring born to pair-fed dams have a reduction in adiposity and an altered gut microbiome, while only female offspring born to pair-fed dams have decreased circulating leptin and white adipose tissue inflammatory cytokines. These sexually dimorphic results suggest that reduction in the maternal obesogenic environment in early pregnancy may play a greater role in female BPH/5 sex-dependent cardiometabolic outcomes than males. Reprograming females may mitigate the transgenerational progression of cardiometabolic disease.
摘要子痫前期 (PE) 是一种影响全球 2-8%孕妇的高血压疾病。其特征是妊娠后半期新发生的高血压，是孕产妇和胎儿发病率/死亡率的主要原因。母体肥胖增加了 PE 的风险，并以性别依赖的方式成为儿童肥胖和潜在后代心脏代谢并发症的关键预测因素。母体肥胖环境的影响，加上 PE 的发生，对后代成年期的发育尚不清楚。自发性表现出妊娠晚期高血压、胎儿死亡和生长受限以及过度妊娠体重增加的肥胖 BPH/5 小鼠。当从受孕开始通过限食对 BPH/5 雌性进行体重减轻时，BPH/5 雌性的妊娠结局得到改善。我们假设，通过在怀孕期间对 BPH/5 母鼠进行限食，雌性和雄性 BPH/5 后代之间的表型差异可以受到影响。BPH/5 限食母鼠的窝产仔数增加，胎儿体重增加。自由采食母鼠所生的 BPH/5 后代具有相似的性别比例、体重和粪便微生物组，以及血压升高，而限食母鼠所生的后代血压降低。限食母鼠所生的 BPH/5 雄性和雌性后代的肥胖程度均降低，肠道微生物组发生改变，而只有限食母鼠所生的雌性后代的循环瘦素和白色脂肪组织炎症细胞因子减少。这些性别二态性结果表明，在妊娠早期减少母体肥胖环境可能对女性 BPH/5 依赖性心脏代谢结局的影响大于男性。重新编程女性可能会减轻心脏代谢疾病的代际进展。
