The Making of Mother’s Milk

At BIOMILQ, we are developing technology for the production of milk outside the body — an innovation with profound implications for how we feed our babies, and how we feed our planet. With nature as the ideal to which we aspire, we spend a lot of time thinking about how milk is made inside the body, and what factors influence this remarkable process. This month, we want to share our fascination by providing a glimpse into the gland that makes us mammals.

With so many misconceptions about lactation and infant feeding, this article serves to share the fundamental physiology behind milk synthesis.

By understanding the behind-the-scenes of milk-making, we hope that moms cut themselves some slack, recognizing that there are many biological reasons for breastfeeding struggles, and that there is more than one way to feed a baby.

Across the animal kingdom, mammals are unique in their ability to produce a complete source of nutrition for their young within their own bodies — an ability that has afforded them a distinct evolutionary advantage, allowing mammals to thrive in almost every habitat on Earth. The milks of each species are as diverse as the class Mammalia itself, providing the precise blend of nutrients and bioactive molecules needed to support the growth and development of animals that range in total body mass from less than a tenth of a pound for the Etruscan shrew1 to a whopping 400,000 pounds for the blue whale (2).

The whale and the shrew spend their lives in completely different environments with completely different resources at their disposal, but both share the same remarkable physiology for the assimilation of those resources into a precisely crafted milk that is tuned to meet the needs of the infant, protect the mother’s own reserves, and promote the wellbeing of both.

The production of milk within the mammary gland is an elegantly orchestrated process that converts food from the mother’s environment into food for her young, whose immature body struggles to consume the nutrients in an unprocessed form. Despite the dramatic differences in scale and the high level of compositional variability of milks across mammalian species, the physiology that underlies the process of milk production is remarkably consistent.

The mammary gland is a dynamic organ that undergoes dramatic changes in preparation for the arrival of a hungry baby (3). Hormonal changes during pregnancy direct the cells that make up the tissue to multiply and mobilize, establishing the system that will deliver milk to the suckling newborn (4). Prior to arrival of the baby, compartments for the collection and storage of milk are formed within the breast tissue (5), and a branching network of ducts connects them to the nipple. As the final step of preparation for lactation, the tissue prepares to respond to hormonal triggers, brought on by the birth, to start producing milk.

By the time the baby is born, each of the newly formed compartments within the mammary gland is lined by a single layer of mammary epithelial cells, which are mainly responsible for milk production (6). When prolactin, a key component of the hormonal triggers, is delivered through the mother’s bloodstream, the cells start to absorb nutrients from the mother and convert them into the components of milk. The milk then accumulates in the compartments of the mammary gland, where it waits for the baby’s cue. Once lactation is established, a variety of biochemical and mechanical factors help sustain milk production until the baby no longer relies on mother’s milk.

Simple diagram of mammary epithelial cells absorbing nutrients (bottom) then converting them into the components of milk (top).

While this all may sound simple, moms deserve far more credit because the lactation process uses an enormous amount of energy (7). Production of the thousands of unique molecules present in milk is a demanding process that could deplete the mother’s own resources if it were not tightly controlled to ensure that just enough milk is produced. Control of milk production involves dramatic changes in gene expression within the mammary gland and metabolic changes throughout the body in response to the intimate relationship between the mother, her baby, and their environment (8).

And herein lie the differences between the massive blue whale and the tiny Etruscan shrew. While the underlying physiology is similar, the vast differences in the volume and composition of their milks are the result of a) differences in the nutrients in their environments, and b) the genetic instructions that dictate how the mother’s nutrients are absorbed and transformed into nutrition for her baby (9).

The balance of these activities ensures that just the right amount of milk, with just the right nutritional profile, is produced at just the right time to nourish the baby — we’re in awe of this species-specific balancing act.

Considering that milk is so intricately controlled and tailored to the needs of the infant, what are we to make of our 2000-year history of using milks from other species to feed human babies?(10). Humans are quite unique among other mammals in our use of alternative modes of infant feeding. Modern infant formula is most commonly derived from cow’s milk and has a long history as a safe and effective alternative to breastfeeding when it is prepared correctly. Humans benefit from a high level of dietary flexibility compared with other mammals (11), perhaps contributing to the acceptability of the milks of other species as breast milk alternatives.

While adaptability is necessary for the survival of any species, the dietary flexibility of humans is quite impressive. Our ability to use complementary feeding practices, in addition or in place of breastmilk, may signify a lower level of evolutionary pressure for successful lactation compared with other mammals, whose babies do not have other nutrition sources. Because our babies can continue to thrive via alternative feeding sources, a diversity of lactation patterns is observed among the human population — milk-producing genes no longer determine life or death. Indeed, recent studies have identified a number of genes that are differentially expressed in women with low milk supply (12, 13), one of the most commonly reported reasons that women stop breastfeeding (14).

Despite the predominant “breast is best” mindset, from an evolutionary standpoint, feeding babies infant formula is not unnatural, but is rather a useful way to leverage our evolutionary advantage of dietary flexibility. This adaptability keeps our babies alive while preserving our energy so that we can devote our resources to meeting the full range of our babies’ needs.

We hope that a look into how milk is produced in the body offers some peace of mind to those with the oh-so-common struggle to produce enough milk (14). Though there are many physiological causes that affect a woman’s ability to produce enough milk to feed her child, low milk supply is often assumed by healthcare providers to simply be perceived. This assumption is harmful to mothers and babies, as it may pressure a mother to override her perceptions about her own body and the needs of her baby. The evidence supports a physiological explanation for low milk supply that will not be overcome by gaslighting women about their own experience or suggesting that they should just try harder.

As difficult as it is to accept, most women have far less control over their lactation than they would like.

Instead of questioning a mother’s ability to decide what is best for her baby, we must celebrate the enormous effort it takes to feed a baby by any means, we must recognize the physiological nuances that affect lactation, and we must support moms whose genes happen to suck (pun-intended) at promoting optimal milk production.

In an upcoming post, we will further explore low milk supply and discuss the vital importance of trusting mothers to recognize when the needs of their babies are not being met, rather than shaming them for how they choose to meet them.

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1. Jurgens KD. Etruscan shrew muscle: the consequences of being small. J Exp Biol. 2002;205(Pt 15):2161–2166. 2. Meet the biggest animal in the world. World Wildlife Foundation.,to%2098%20feet%20in%20length. Accessed February 14, 2021. 3. Alex A, Bhandary E, McGuire KP. Anatomy and Physiology of the Breast during Pregnancy and Lactation. Adv Exp Med Biol. 2020;1252:3–7. 4. Myllymaki SM, Mikkola ML. Inductive signals in branching morphogenesis — lessons from mammary and salivary glands. Curr Opin Cell Biol. 2019;61:72–78. 5. Stelwagen K, Singh K. The role of tight junctions in mammary gland function. J Mammary Gland Biol Neoplasia. 2014;19(1):131–138. 6. Pang WW, Hartmann PE. Initiation of human lactation: secretory differentiation and secretory activation. J Mammary Gland Biol Neoplasia. 2007;12(4):211–221. 7. Dewey KG. Energy and protein requirements during lactation. Annu Rev Nutr. 1997;17:19–36. 8. Shin HY, Hennighausen L, Yoo KH. STAT5-Driven Enhancers Tightly Control Temporal Expression of Mammary-Specific Genes. J Mammary Gland Biol Neoplasia. 2019;24(1):61–71. 9. Jenness R. Lactational Performance of Various Mammalian Species. J Dairy Sci. 1986;69:869–885. 10. Stevens EE, Patrick TE, Pickler R. A history of infant feeding. J Perinat Educ. 2009;18(2):32–39. 11. Turner BL, Thompson AL. Beyond the Paleolithic prescription: incorporating diversity and flexibility in the study of human diet evolution. Nutr Rev. 2013;71(8):501–510. 12. Twigger AJ, Hepworth AR, Lai CT, et al. Gene expression in breastmilk cells is associated with maternal and infant characteristics. Sci Rep. 2015;5:12933. 13. Geddes DTT, A-J.; Savigni, D. L.; Kent, J. C.; Kakulas, F. Milk cell gene expression of mothers with low breast milk production. FASEB Journal. 2018;31(S1):457. 14. Brand E, Kothari C, Stark MA. Factors related to breastfeeding discontinuation between hospital discharge and 2 weeks postpartum. J Perinat Educ. 2011;20(1):36–44.

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