Beckers Kalie F, Gomes Viviane C L, Crissman Kassandra J Raven, Adams Daniella M, Liu Chin-Chi, Del Piero Fabio, Butler Scott D, Sones Jenny L
Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United States.
Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United States.
Front Pediatr. 2021 Sep 22;9:636143. doi: 10.3389/fped.2021.636143. eCollection 2021.
Preeclampsia (PE) is a hypertensive disorder of pregnancy occurring in approximately 10% of women worldwide. While it is life threatening to both the mother and baby, the only effective treatment is delivery of the placenta and fetus, which is often preterm. Maternal obesity is a risk factor for PE, and the effects of both on offspring are long standing with increased incidence of cardiometabolic disease in adulthood. Obese BPH/5 mice spontaneously exhibit excessive gestational weight gain and late-gestational hypertension, similar to women with PE, along with fetal growth restriction and accelerated compensatory growth in female offspring. We hypothesized that BPH/5 male offspring will demonstrate cardiovascular and metabolic phenotypes similar to BPH/5 females. As previously described, BPH/5 females born to -fed dams are overweight with hyperphagia and increased subcutaneous, peri-renal, and peri-gonadal white adipose tissue (WAT) and cardiomegaly compared to age-matched adult female controls. In this study, BPH/5 adult male mice have similar body weights and food intake compared to age-matched control mice but have increased inflammatory subcutaneous and peri-renal WAT and signs of cardiovascular disease: left ventricular hypertrophy and hypertension. Therefore, adult male BPH/5 do not completely phenocopy the cardiometabolic profile of female BPH/5 mice. Future investigations are necessary to understand the differences observed in BPH/5 male and female mice as they age. In conclusion, the impact of fetal programming due to PE has a transgenerational effect on both male and female offspring in the BPH/5 mouse model. The maternal obesogenic environment may play a role in PE pregnancy outcomes, including offspring health as they age.
子痫前期(PE)是一种妊娠期高血压疾病,全球约10%的女性会发生。虽然它对母亲和胎儿都有生命威胁,但唯一有效的治疗方法是娩出胎盘和胎儿,而这往往是早产。孕妇肥胖是PE的一个风险因素,两者对后代的影响是长期的,会增加成年后患心脏代谢疾病的几率。肥胖的BPH/5小鼠会自发出现过度的孕期体重增加和妊娠晚期高血压,类似于患PE的女性,同时伴有胎儿生长受限和雌性后代的加速代偿性生长。我们假设BPH/5雄性后代会表现出与BPH/5雌性相似的心血管和代谢表型。如前所述,与年龄匹配的成年雌性对照相比,由高脂饮食喂养的母鼠所生的BPH/5雌性超重,有食欲亢进、皮下、肾周和性腺周围白色脂肪组织(WAT)增加以及心脏肥大。在本研究中,与年龄匹配的对照小鼠相比,BPH/5成年雄性小鼠体重和食物摄入量相似,但皮下和肾周WAT炎症增加以及有心血管疾病迹象:左心室肥大和高血压。因此,成年雄性BPH/5并没有完全复制雌性BPH/5小鼠的心脏代谢特征。有必要进行进一步研究以了解随着BPH/5雄性和雌性小鼠年龄增长所观察到的差异。总之,PE导致的胎儿编程对BPH/5小鼠模型中的雄性和雌性后代都有跨代影响。母体致肥胖环境可能在PE妊娠结局中起作用,包括后代随着年龄增长的健康状况。