Sullivan Rhea, Confair Alexandra, Hicks Steven D
Department of Pediatrics, Penn State College of Medicine, Hershey, PA, United States of America.
PLoS One. 2024 Jun 13;19(6):e0305421. doi: 10.1371/journal.pone.0305421. eCollection 2024.
Human milk is optimal for infant nutrition. However, many mothers cease breastfeeding because of low milk supply (LMS). It is difficult to identify mothers at risk for LMS because its biologic underpinnings are not fully understood. Previously, we demonstrated that milk micro-ribonucleic acids (miRNAs) may be related to LMS. Transforming growth factor beta (TGFβ) also plays an important role in mammary involution and may contribute to LMS. We performed a longitudinal cohort study of 139 breastfeeding mothers to test the hypothesis that milk levels of TGFβ would identify mothers with LMS. We explored whether TGFβ impacts the expression of LMS-related miRNAs in cultured human mammary epithelial cells (HMECs). LMS was defined by maternal report of inadequate milk production, and confirmed by age of formula introduction and infant weight trajectory. Levels of TGF-β1 and TGF-β2 were measured one month after delivery. There was a significant relationship between levels of TGF-β1 and LMS (X2 = 8.92, p = 0.003) on logistic regression analysis, while controlling for lactation stage (X2 = 1.28, p = 0.25), maternal pre-pregnancy body mass index (X2 = 0.038, p = 0.84), and previous breastfeeding experience (X2 = 7.43, p = 0.006). The model accounted for 16.8% of variance in the data (p = 0.005) and correctly predicted LMS for 84.6% of mothers (22/26; AUC = 0.72). Interactions between TGF-β1 and miR-22-3p displayed significant effect on LMS status (Z = 2.67, p = 0.008). Further, incubation of HMECs with TGF-β1 significantly reduced mammary cell number (t = -4.23, p = 0.003) and increased levels of miR-22-3p (t = 3.861, p = 0.008). Interactions between TGF-β1 and miR-22-3p may impact mammary function and milk levels of TGF-β1 could have clinical utility for identifying mothers with LMS. Such information could be used to provide early, targeted lactation support.
母乳是婴儿营养的最佳选择。然而，许多母亲因乳汁供应不足（LMS）而停止母乳喂养。由于LMS的生物学基础尚未完全了解，因此很难识别有LMS风险的母亲。此前，我们证明乳汁中的微小核糖核酸（miRNA）可能与LMS有关。转化生长因子β（TGFβ）在乳腺退化中也起重要作用，可能导致LMS。我们对139名母乳喂养的母亲进行了一项纵向队列研究，以检验乳汁中TGFβ水平可识别LMS母亲的假设。我们探讨了TGFβ是否会影响培养的人乳腺上皮细胞（HMEC）中LMS相关miRNA的表达。LMS由母亲报告的乳汁分泌不足来定义，并通过开始配方奶喂养的年龄和婴儿体重轨迹来确认。在分娩后一个月测量TGF-β1和TGF-β2的水平。在逻辑回归分析中，控制泌乳阶段（X2 = 1.28，p = 0.25）、母亲孕前体重指数（X2 = 0.038，p = 0.84）和既往母乳喂养经历（X2 = 7.43，p = 0.006）后，TGF-β1水平与LMS之间存在显著关系（X2 = 8.92，p = 0.003）。该模型解释了数据中16.8%的方差（p = 0.005），并正确预测了84.6%的母亲的LMS情况（22/26；AUC = 0.72）。TGF-β1与miR-22-3p之间的相互作用对LMS状态有显著影响（Z = 2.67，p = 0.008）。此外，用TGF-β1孵育HMEC可显著减少乳腺细胞数量（t = -4.23，p = 0.003）并增加miR-22-3p的水平（t = 3.861，p = 0.008）。TGF-β1与miR-22-3p之间的相互作用可能影响乳腺功能，乳汁中TGF-β1水平可能对识别LMS母亲具有临床应用价值。此类信息可用于提供早期、有针对性的泌乳支持。
