Multiparity induces persistent myocardial structural, functional and transcriptomic remodelling

We postulated that the repetitive biological and hemodynamic impact of multiple pregnancies could cause persistent myocardial remodelling providing a substrate for subsequent HFpEF. Here we report that C57Bl/6J female mice at 24 months of age with history of multiple pregnancies have a different transcriptomic profile combined with diastolic dysfunction, and persistent remodeling in the absence of on going stimulus, compared to virgin age matched mice. 128 genes were differentially expressed in the the multiparous mice.

The 64 upreguated and 64 downregulated genes were associated organic anion/ion transport and extra cellular matrix regulation pathway. These genes were also involved in biological processes such as ERBB2-3 signaling and actin polymerisation dependent cell motility, and were associated with 5 cardiac related disease pertubations in the top ten diesease pertubations in GEO UP including dilated cardiomyopathy. Therefore multiparity could provide a potential foundation for heart failure phenotypes including HFpEF later in life.