Related Experiment Video
Updated: Apr 12, 2026
Murine Model of Thoracic Aortic Dissection Induced by Oral β-Aminopropionitrile and Subcutaneous Angiotensin II Infusion
Published on: May 16, 2025
Antenatal maternal low protein diet: ACE-2 in the mouse lung and sexually dimorphic programming of hypertension
Ravi Goyal1,2, Jonathan Van-Wickle3, Dipali Goyal4
1Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA, 92350, USA. rgoyal@llu.edu.
Insights
Maternal low protein diet during pregnancy reduced pup birth weight. Female offspring developed hypertension due to reduced ACE-2 in lungs, unlike males, suggesting a sexually dimorphic programming mechanism.
Area of Science:
- Physiology
- Developmental Biology
- Cardiovascular Health
Background:
- Elevated blood pressure (hypertension) is a significant global health issue.
- In-utero under-nutrition is a potential contributor to hypertension development.
- The pulmonary renin-angiotensin system's role in hypertension programming requires further investigation.
Purpose of the Study:
- To investigate if antenatal maternal low protein diet (MLPD) sexually dimorphically programs pulmonary renin-angiotensin system components.
- To determine the link between MLPD and hypertension development in offspring.
- To explore the role of microRNAs in this programming.
Main Methods:
- Pregnant mice received either a normal or a 50% protein-restricted diet.
- Offspring blood pressure was measured non-invasively from 18-24 weeks postnatal.
- Pulmonary mRNA and protein expression of renin-angiotensin system components, including ACE-2, were analyzed.
- MicroRNA levels complementary to ACE-2 were quantified.
Main Results:
- Antenatal MLPD significantly reduced pup birth weight in both sexes.
- Female offspring developed hypertension, while males did not.
- Female offspring showed reduced pulmonary ACE-2 protein but unchanged mRNA levels.
- Upregulation of miRNA 429 was observed in female offspring lungs.
- Male offspring exhibited unaltered ACE-2 mRNA and protein expression.
Conclusions:
- Antenatal MLPD leads to sexually dimorphic programming of hypertension in mice.
- Reduced pulmonary ACE-2 in female offspring, potentially mediated by miRNA 429, is a key mechanism.
- This study highlights the long-term cardiovascular consequences of maternal nutrition during gestation.
Abstract:
Elevated blood pressure is an important global health problem, and in-utero under-nutrition may be an important factor in the pathogenesis of hypertension. In the present study, we tested the hypothesis that antenatal maternal low protein diet (MLPD) leads to sexually dimorphic developmental programming of the components of the pulmonary renin-angiotensin system. This may be important in the antenatal MLPD-associated development of hypertension. In pregnant mice, we administered normal (control) and isocaloric 50% protein restricted diet, commencing one week before mating and continuing until delivery of the pups. From the 18th to 24th week postnatal, we measured blood pressure in the offspring by use of a non-invasive tail-cuff method. In the same mice, we examined the mRNA and protein expression of the key components of the pulmonary renin-angiotensin system. Also, we examined microRNA complementary to angiotensin converting enzymes (ACE) 2 in the offspring lungs. Our results demonstrate that as a consequence of antenatal MLPD: 1) pup birthweight was significantly reduced in both sexes. 2) female offspring developed hypertension, but males did not. 3) In female offspring, ACE-2 protein expression was significantly reduced without any change in the mRNA levels. 4) miRNA 429, which has a binding site on ACE-2 - 3' UTR was significantly upregulated in the female antenatal MLPD offspring. 5) In males, ACE-2 mRNA and protein expression were unaltered. We conclude that in the mouse, antenatal MLPD-induced reduction of ACE-2 in the female offspring lung may be an important mechanisms in sexually dimorphic programming of hypertension.
