Cardiometabolic Phenotypic Differences in Male Offspring Born to Obese Preeclamptic-Like BPH/5 Mice
Kalie F Beckers1, Viviane C L Gomes1, Kassandra J Raven Crissman1
1Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United States.
Insights
Preeclampsia and maternal obesity can program offspring for long-term health issues. In mice, male offspring showed cardiovascular problems but not the full metabolic profile seen in females.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Cardiovascular Science
Background:
- Preeclampsia (PE) affects 10% of pregnancies globally, posing risks to mother and child.
- Maternal obesity is a risk factor for PE, with lasting cardiometabolic effects on offspring.
- The BPH/5 mouse model mimics PE, showing gestational issues and altered offspring growth.
Purpose of the Study:
- To investigate if BPH/5 male offspring develop cardiovascular and metabolic phenotypes similar to BPH/5 females.
- To compare the long-term health outcomes of male and female offspring from obese dams with PE-like conditions.
Main Methods:
- Utilized the BPH/5 mouse model, which spontaneously develops PE-like symptoms.
- Compared adult male BPH/5 offspring to age-matched controls and previously studied female BPH/5 offspring.
- Assessed body weight, food intake, adipose tissue (WAT), and cardiovascular parameters (left ventricular hypertrophy, hypertension).
Main Results:
- BPH/5 male mice had similar body weight and food intake as controls.
- Male offspring exhibited increased inflammatory subcutaneous and peri-renal WAT.
- Signs of cardiovascular disease, including left ventricular hypertrophy and hypertension, were observed in male offspring.
Conclusions:
- Adult male BPH/5 mice do not fully replicate the cardiometabolic profile of female BPH/5 mice.
- Fetal programming due to PE has transgenerational effects on both male and female offspring in this model.
- The maternal obesogenic environment may influence PE outcomes and long-term offspring health.
Abstract:
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 ad libitum-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.
