Department of Pediatrics, Penn State College of Medicine, Hershey, PA 17033, USA.
Department of Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA.
Nutrients. 2023 Jan 21;15(3):567. doi: 10.3390/nu15030567.
Low milk supply (LMS) is associated with early breastfeeding cessation; however, the biological underpinnings in the mammary gland are not understood. MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally downregulate gene expression, and we hypothesized the profile of miRNAs secreted into milk reflects lactation performance. Longitudinal changes in milk miRNAs were measured using RNAseq in women with LMS ( = 47) and adequate milk supply (AMS; = 123). Relationships between milk miRNAs, milk supply, breastfeeding outcomes, and infant weight gain were assessed, and interactions between milk miRNAs, maternal diet, smoking status, and BMI were determined. Women with LMS had lower milk volume ( = 0.003), were more likely to have ceased breast feeding by 24 wks ( = 0.0003) and had infants with a lower mean weight-for-length z-score ( = 0.013). Milk production was significantly associated with milk levels of miR-16-5p (R = -0.14, adj = 0.044), miR-22-3p (R = 0.13, adj = 0.044), and let-7g-5p (R = 0.12, adj = 0.046). Early milk levels of let-7g-5p were significantly higher in mothers with LMS (adj = 0.0025), displayed an interaction between lactation stage and milk supply ( < 0.001), and were negatively related to fruit intake ( = 0.015). Putative targets of let-7g-5p include genes important to hormone signaling, RNA regulation, ion transport, and the extracellular matrix, and down-regulation of two targets (PRLR and IGF2BP1/IMP1) was confirmed in mammary cells overexpressing let-7g-5p in vitro. Our data provide evidence that milk-derived miRNAs reflect lactation performance in women and warrant further investigation to assess their utility for predicting LMS risk and early breastfeeding cessation.
低奶量（LMS）与早期母乳喂养中断有关；然而，乳腺中的生物学基础尚不清楚。microRNAs（miRNAs）是一种小的非编码 RNA，可以转录后下调基因表达，我们假设分泌到乳汁中的 miRNAs 谱反映了哺乳表现。使用 RNAseq 测量了 LMS（n = 47）和充足奶量（AMS；n = 123）女性的乳汁 miRNA 的纵向变化。评估了乳汁 miRNA 与乳汁供应、母乳喂养结果和婴儿体重增加之间的关系，并确定了乳汁 miRNA 与母体饮食、吸烟状况和 BMI 之间的相互作用。LMS 女性的奶量较低（P = 0.003），24 周时更有可能停止母乳喂养（P = 0.0003），且婴儿的平均体重长度 Z 评分较低（P = 0.013）。乳汁产量与乳汁 miR-16-5p（R = -0.14，adj P = 0.044）、miR-22-3p（R = 0.13，adj P = 0.044）和 let-7g-5p（R = 0.12，adj P = 0.046）水平显著相关。LMS 女性早期乳汁中的 let-7g-5p 水平显著较高（adj P = 0.0025），在泌乳阶段和乳汁供应之间表现出交互作用（P < 0.001），并且与水果摄入量呈负相关（P = 0.015）。let-7g-5p 的假定靶标包括对激素信号、RNA 调节、离子转运和细胞外基质重要的基因，并且在体外过表达 let-7g-5p 的乳腺细胞中，两个靶标（PRLR 和 IGF2BP1/IMP1）的下调得到了证实。我们的数据提供了证据，表明乳汁衍生的 miRNAs 反映了女性的哺乳表现，值得进一步研究，以评估它们预测 LMS 风险和早期母乳喂养中断的效用。
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