Q Bartlett Alexandra, Vesco Kimberly K, Purnell Jonathan Q, Francisco Melanie, Goddard Erica, Guan Xiangnan, DeBarber Andrea, Leo Michael C, Baetscher Eric, Rooney William, Naugler Willscott, Guimaraes Alexander R, Catalano Patrick, Xia Zheng, Schedin Pepper
Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR 97239.
Center for Health Research, Kaiser Permanente Northwest, Portland, OR 97227.
Proc Natl Acad Sci U S A. 2021 Nov 30;118(48). doi: 10.1073/pnas.2107269118.
During pregnancy, the rodent liver undergoes hepatocyte proliferation and increases in size, followed by weaning-induced involution via hepatocyte cell death and stromal remodeling, creating a prometastatic niche. These data suggest a mechanism for increased liver metastasis in breast cancer patients with recent childbirth. It is unknown whether the human liver changes in size and function during pregnancy and weaning. In this study, abdominal imaging was obtained in healthy women at early and late pregnancy and postwean. During pregnancy time points, glucose production and utilization and circulating bile acids were measured. Independently of weight gain, most women's livers increased in size with pregnancy, then returned to baseline postwean. Putative roles for bile acids in liver growth and regression were observed. Together, the data support the hypothesis that the human liver is regulated by reproductive state with growth during pregnancy and volume loss postwean. These findings have implications for sex-specific liver diseases and for breast cancer outcomes.
在怀孕期间，啮齿动物的肝脏会经历肝细胞增殖并增大，随后在断奶时通过肝细胞死亡和基质重塑发生退化，形成一个促转移微环境。这些数据提示了近期分娩的乳腺癌患者肝转移增加的一种机制。目前尚不清楚人类肝脏在怀孕和断奶期间大小和功能是否会发生变化。在本研究中，对健康女性在妊娠早期、晚期及断奶后进行了腹部成像检查。在妊娠各时间点，测量了葡萄糖生成与利用情况以及循环胆汁酸水平。与体重增加无关，大多数女性的肝脏在怀孕期间增大，断奶后恢复至基线水平。观察到了胆汁酸在肝脏生长和退化中的潜在作用。总体而言，这些数据支持这样一种假说，即人类肝脏受生殖状态调控，在怀孕期间生长，断奶后体积减小。这些发现对性别特异性肝脏疾病以及乳腺癌结局具有重要意义。
