Biological underpinnings of breastfeeding challenges: the role of genetics, diet, and environment on lactation physiology

Abstract

Lactation is a dynamic process that has evolved to produce a complex biological fluid that provides nutritive and nonnutritive factors to the nursing offspring. It has long been assumed that once lactation is successfully initiated, the primary factor regulating milk production is infant demand. Thus, most interventions have focused on improving breastfeeding education and early lactation support. However, in addition to infant demand, increasing evidence from studies conducted in experimental animal models, production animals, and breastfeeding women suggests that a diverse array of maternal factors may also affect milk production and composition. In this review, we provide an overview of our current understanding of the role of maternal genetics and modifiable factors, such as diet and environmental exposures, on reproductive endocrinology, lactation physiology, and the ability to successfully produce milk. To identify factors that may affect lactation in women, we highlight some information gleaned from studies in experimental animal models and production animals. Finally, we highlight the gaps in current knowledge and provide commentary on future research opportunities aimed at improving lactation outcomes in breastfeeding women to improve the health of mothers and their infants.

Keywords: diet; environment; genetics; lactation; mammary gland.

Fig. 1.

Maternal factors that can lead to lactation insufficiency. Lactation insufficiency is a condition in which lactation is insufficient or unsuccessful due to inadequate milk production. A and B: images of hematoxylin and eosin-stained mouse mammary gland tissues represent a functional mammary gland undergoing successful lactation (A) and a mammary gland with impaired mammary differentiation and milk secretion that results in lactation insufficiency (B). C: list summarizing genetic, dietary, and environmental factors that have been shown to affect lactation outcomes. PRLR, prolactin receptor; Jak2, Janus kinase 2; SOCS2, suppressor of cytokine signaling 2; STAT, signal transducer and activator of transcription; ATF4, activating transcription factor 4; IGFBP-4, insulin-like growth factor-binding protein 4; IRF1, interferon regulatory factor 1; LIFR, leukemia inhibitory factor receptor; OSMR, oncostatin M receptor; PTK2, protein tyrosine kinase 2; mTOR, mammalian target of rapamycin; Gsk3, glycogen synthase kinase 3; LeuRS, leucyl-tRNA synthetase; PPARγ, peroxisome proliferator-activated receptor-γ; GH, growth hormone; OXTR, oxytocin receptor; FGF2, fibroblast growth factor 2; VDR, vitamin D receptor; ZnT2, zinc transporter 2; DGAT1, diacylglycerol O-acyltransferase 1; apo4, apolipoprotein 4; apoE, apolipoprotein E; FADS, fatty acid desaturase; LCPUFA, long-chain polyunsaturated fatty acids; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; MCFA, medium-chain fatty acid; AA, arachidonic Acid; BPA, bisphenol A; PBDE, polybrominated diphenyl ethers (PBDE); PFOA, perfluorooctanoic acid; PCDD, polychlorinated dibenzo-p-dioxins; PCDF, polychlorinated dibenzofurans; PCB, polychlorinated biphenyls; DDE, dichlorodiphenyl dichloroethene.