ABSTRACT
Maternal mortality rates are at an all-time high across the world and are set to increase in subsequent years. Cardiovascular disease is the leading cause of death during pregnancy and postpartum, especially in the United States. Therefore, understanding the physiological changes in the cardiovascular system during normal pregnancy is necessary to understand disease-related pathology. Significant systemic and cardiovascular physiological changes occur during pregnancy that are essential for supporting the maternal-fetal dyad. The physiological impact of pregnancy on the cardiovascular system has been examined in both experimental animal models and in humans. However, there is a continued need in this field of study to provide increased rigor and reproducibility. Therefore, these guidelines aim to provide information regarding best practices and recommendations to accurately and rigorously measure cardiovascular physiology during normal and cardiovascular disease-complicated pregnancies in human and animal models.
Subject(s)
Cardiovascular Physiological Phenomena , Postpartum Period , Pregnancy , Humans , Female , Animals , Pregnancy Complications, Cardiovascular/physiopathology , Cardiovascular System/physiopathology , Cardiovascular Diseases/physiopathology , Cardiovascular Diseases/diagnosisABSTRACT
OBJECTIVE: Epidemiological studies suggest that lactation is associated with long-term maternal health benefits. To avoid confounders in human studies, we used a previously characterized murine model to investigate the long-term effect of lactation on both cardiovascular function and adiposity. STUDY DESIGN: After the delivery of the pups, CD-1 female mice were randomly divided into two groups: lactated and nonlactated (NL). Before pregnancy and at 9 months postdelivery, blood pressure was measured using a tail cuff, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were assessed by computed tomography (CT), echocardiography was performed using microultrasound, and cholesterol panels and fasting blood glucose were measured. The data were analyzed using Student's t-test (significance at p < 0.05). RESULTS: There were no differences in baseline parameters between the two groups. At 9 months postdelivery, the NL group weighed significantly more (p = 0.03) and demonstrated a significantly lower cardiac output (p = 0.05) and ejection fraction (p = 0.03). The mice in the NL group also had higher VAT (p < 0.01) and SAT percentiles (p = 0.03). Fasting glucose (p = 0.01) and low-density lipoprotein (p = 0.01) were significantly higher in the NL group at 9 months. CONCLUSION: Our results show the benefit of lactation is not just limited to the immediate postpartum period but it also extends into midlife in a murine model.
Subject(s)
Adiposity/physiology , Blood Pressure/physiology , Cardiac Output/physiology , Lactation/physiology , Animals , Echocardiography , Female , Intra-Abdominal Fat/diagnostic imaging , Mice , Mice, Inbred Strains , Models, Animal , Subcutaneous Fat/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
The objective of this study was to evaluate whether the renin-angiotensin system (RAS) is associated with maternal cardioprotective phenotype observed in post-lactated mice later in life. Following the delivery, CD-1 female mice were randomized to one of the following groups: lactated (nursed pups for 3 weeks, n = 10) or non-lactated (pups were removed after birth, n = 10). The mice were sacrificed 6 months after the delivery, and tissues were collected. Protein levels of angiotensinogen, angiotensin type 1 and 2 receptors (AT1R, AT2R), angiotensin converting enzymes (ACE, ACE2), and MAS receptor were determined using Western blot. Results were analyzed using Student's t-test and Mann-Whitney test as appropriate (significance: P < 0.05). Angiotensinogen levels were significantly lower in the liver (P = 0.0002), and ACE was significantly decreased in the lungs (P = 0.04) and kidney (P = 0.001) from lactated mice as compared to non-lactated. The levels of AT2R in the kidney (P = 0.02) and visceral adipose tissue (VAT, P = 0.04), the ACE 2 in the VAT (P = 0.03) and heart (P = 0.04), and MAS receptor in VAT (P = 0.02) were significantly elevated in tissues from lactated mice. No other differences were found. Lactation led to the upregulation and downregulation of selected RAS components in lactated mice as compared to non-lactated group and may be a contributing factor to maternal cardioprotective phenotype later in life. Further studies are needed to dissect the mechanisms between lactation and the long-term maternal cardiometabolic benefits, which could lead to the therapies to prevent cardiovascular disease in women.
Subject(s)
Kidney/metabolism , Lactation/physiology , Renin-Angiotensin System/physiology , Angiotensinogen/metabolism , Animals , Female , Liver/metabolism , Mice , Peptidyl-Dipeptidase A/metabolism , Proto-Oncogene Mas , Proto-Oncogene Proteins/metabolism , Receptor, Angiotensin, Type 1/metabolism , Receptor, Angiotensin, Type 2/metabolism , Receptors, G-Protein-Coupled/metabolismABSTRACT
Although it has been widely accepted that pregnancies with complications are associated with increased maternal cardiovascular risk later in life, there is no consensus if noncomplicated pregnancy followed by lactation plays a protective role or is a risk factor. The objective of this study was to investigate the effects of normal pregnancy and lactation on long-term maternal health in a mouse model. CD-1 mice were allocated to breeding (primigravid [PG]) and nonbreeding (nulligravid [NG]) groups. The PG group proceeded through normal pregnancy and delivery. Using a telemetry system, blood pressure (BP) was analyzed in the PG group at 6 months postpartum and in age-matched NG mice. Serum analytes, gene expressions, and protein levels were determined using appropriate analysis methods. Primigravid mice had significantly lower systolic and diastolic BP and fasting glucose levels. Circulating oxytocin (OXT) levels were significantly higher in PG mice. Oxt gene expression was significantly higher in the heart and aorta and lower in visceral adipose tissue (VAT) from PG mice. The oxytocin receptor ( Oxtr) gene expression was significantly higher in the heart, aorta, and VAT from PG animals. The level of Oxtr DNA hypermethylation and the expression of mmu-miR-29a were significantly lower in the hearts of PG mice. In PG VAT, glucose transporter-4 expression was significantly higher. Our study demonstrates that a history of normal pregnancy followed by lactation was associated with lower maternal cardiovascular risk factors later in life in female mouse.