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Maternal hypothyroidism (MH) could adversely affect the cardiac disease responses of the progeny. This study tested the hypothesis that MH reduces early postnatal cardiomyocyte (CM) proliferation so that the adult heart of MH progeny has a smaller number of larger cardiac myocytes, which imparts adverse cardiac disease responses following injury. Thyroidectomy (TX) was used to establish MH. The progeny from mice that underwent sham or TX surgery were termed Ctrl (control) or MH (maternal hypothyroidism) progeny, respectively. MH progeny had similar heart weight (HW) to body weight (BW) ratios and larger CM size consistent with fewer CMs at postnatal day 60 (P60) compared with Ctrl (control) progeny. MH progeny had lower numbers of EdU+, Ki67+, and phosphorylated histone H3 (PH3)+ CMs, which suggests they had a decreased CM proliferation in the postnatal timeframe. RNA-seq data showed that genes related to DNA replication were downregulated in P5 MH hearts, including bone morphogenetic protein 10 (Bmp10). Both in vivo and in vitro studies showed Bmp10 treatment increased CM proliferation. After transverse aortic constriction (TAC), the MH progeny had more severe cardiac pathological remodeling compared with the Ctrl progeny. Thyroid hormone (T4) treatment for MH mothers preserved their progeny's postnatal CM proliferation capacity and prevented excessive pathological remodeling after TAC. Our results suggest that CM proliferation during early postnatal development was significantly reduced in MH progeny, resulting in fewer CMs with hypertrophy in adulthood. These changes were associated with more severe cardiac disease responses after pressure overload. [ABSTRACT FROM AUTHOR]

Background: Women's parity has been associated with risk of cardiovascular disease (CVD). It is unclear, however, whether it reflects biological effects of childbearing or uncontrolled socio-economic and lifestyle factors associated with childrearing. We assessed the association between number of children and incident CVD outcomes separately in women and men.Methods: In 2004-08, the nationwide China Kadoorie Biobank recruited 0.5 million individuals aged 30-79 years from 10 diverse regions. During 7 years of follow-up, 24 432 incident cases of coronary heart disease (CHD) and 35 736 of stroke were recorded among 489 762 individuals without prior CVD. Multivariable Cox regression models were used to estimate sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for CHD and stroke associated with number of children.Results: Overall, 98% of all participants had children and the mean number of children declined progressively from four in older participants to one or two in younger participants. Compared with childless women, women with children had an increased risk of CHD, but not of stroke [HR (95% CI): 1.14 (1.00; 1.30) and 1.03 (0.92; 1.16)]. Corresponding results for men were 1.20 (1.06; 1.35) and 1.13 (1.03; 1.24), respectively. In individuals with children, there was a log-linear association between number of children and CVD outcomes; in women, each additional child was associated with adjusted HRs of 1.02 (1.01; 1.04) for CHD and 1.02 (1.01; 1.03) for stroke, similar in magnitude to that in men [1.03 (1.01; 1.04) for CHD and 1.02 (1.01; 1.03) for stroke].Conclusion: In Chinese adults, the association between the number of children and risk of CHD and stroke was similar between men and women, suggesting that factors associated with parenthood and childrearing are more likely to affect the risk of CVD outcomes than factors associated with childbearing. [ABSTRACT FROM AUTHOR]