Key result
Prolactin receptor loss causes pregnancy-induced cardiomyopathy with ~45% lower LVEF after multiparity.
Why the study?
Does cardiomyocyte prolactin signaling mediate cardiac adaptation to pregnancy and prevent pregnancy-induced cardiomyopathy in mice?
Does cardiomyocyte prolactin signaling mediate cardiac adaptation to pregnancy and prevent pregnancy-induced cardiomyopathy in mice?
Answers are grounded in this paper and cite their sources.
Cardiomyocyte prolactin signaling is essential for normal cardiac adaptation to pregnancy, and its loss leads to cardiomyopathy after multiple pregnancies in mice.
Background: The heart adapts to pregnancy at transcriptional, metabolic, morphologic, and functional levels, ensuring that demands of both the mother and developing child are adequately met. How extra-cardiac signals coordinate cardiac adaptation to pregnancy is poorly understood. For various maternal tissues, including mammary glands, adipose and pancreatic β-cells, lactogenic hormones act via the prolactin receptor (PRLR) to orchestrate tissue adaptation during pregnancy. Objective: To determine whether cardiomyocyte prolactin signaling is required for cardiac adaptation to pregnancy. Approach: Timed pregnancies were performed in cardiomyocyte-specific PRLR knockout (cmPRLR-KO) and littermate control (CON) female mice at 9 weeks of age. Systolic and diastolic function were assessed by echocardiography at gestation day 16. Immediately following echocardiography, hearts were isolated for gravimetric, histologic, and molecular analyses. In a subset of studies, the impact of multiple (3) sequential pregnancies was investigated in cmPRLR-KO and CON mice. In all experiments, non-pregnant age-matched female mice were assessed in an identical manner. Results: As anticipated, a single pregnancy increased biventricular weight (+17%; p<0.001), cardiomyocyte size (+64%; p<0.001), left ventricular (LV) area (+8%; p=0.045), and cardiac output (+16%; p=0.032) in CON mice. In contrast, pregnancy-induced alterations in these parameters were either abolished or significantly (p<0.05) attenuated in cmPRLR-KO mice. Given impaired cardiac adaptation of cmPRLR-KO mice to a single pregnancy, we hypothesized that this may lead to maladaptation following multiple pregnancies. Consistent with this premise, 3 sequential pregnancies resulted in cardiomyopathy in cmPRLR-KO mice (but not in CON mice), characterized by reduced LV ejection fraction (-45%; p<0.001), increased LV volume (+196%; p<0.001), increased cardiomyocyte size (+69%; p=0.001), and induction of adverse cardiac remodeling markers (e.g., +266% nppa mRNA; p=0.002). Conclusions: Cardiomyocyte prolactin signaling is essential for adaptation of the heart to pregnancy. Loss of cardiomyocyte prolactin signaling precipitates cardiomyopathy following multiple pregnancies.
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Shanmugam et al. (2025) studied Pregnancy-induced cardiac adaptation. Cardiomyocyte-specific PRLR knockout (cmPRLR-KO) vs. Littermate control (CON) mice was evaluated on Cardiac adaptation to pregnancy (biventricular weight, cardiomyocyte size, LV area, cardiac output) (p=<0.05). Cardiomyocyte-specific prolactin receptor knockout in mice abolished normal pregnancy-induced cardiac adaptations and precipitated cardiomyopathy (LVEF -45%, p<0.001) after 3 sequential pregnancies.
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