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.

By understanding the behind-the-scenes of milk-making, we hope that moms cut themselves some slack, recognizing that there are physiological 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 predominantly responsible for milk production (6). Each cell within the layer forms intimate associations with the underlying tissues, as well as with neighboring cells within the lining. These relationships between the cells within the mammary gland set the stage for milk production. A molecular cue circulating within the mother’s blood called prolactin fits like a key in a lock when it encounters a receptor on the surface of the mammary epithelial cell layer, triggering a series of events that activates the cells to absorb nutrients from the mother, convert them into the components of milk, and then transport and secrete the milk into the compartments of the gland. Once lactation is established, a variety of biochemical and mechanical factors help to sustain it until the infant is able to absorb and digest solid foods on their own.

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

This all may sound simple enough, but lactation is a process that demands an enormous amount of energy (7) and involves changes in the expression of thousands of genes (8) in response to the intimate relationship between the mother, her offspring, and their environment. 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 differences in the nutrients that are present in the environment and the genetic programs that control their uptake from the mother’s bloodstream, their bioconversion into milk, and their secretion into the gland (9).

It is the balance of these activities that ensures that for any mammalian species, the right amount of milk, with the right molecular content, is produced at the right time to nourish the baby.

As you might expect, disruption of this balance can have profound consequences for the success of lactation, and thus the survival of the young. In the absence of alternative sources of infant nutrition, strong evolutionary pressure has ensured that milk production is both robust and efficient (10).

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? (11) 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 track record as a safe and effective alternative to breastfeeding when it is prepared correctly. Humans demonstrate high dietary flexibility compared with other mammals (12), perhaps contributing to the acceptability of the milks of other animals as breast milk alternatives.

One possible effect of our widespread use of complementary feeding practices could be a lessened selective pressure for successful lactation compared with other mammals, whose babies will die if milk production is insufficient. Indeed, recent studies have identified a number of genes that are differentially expressed in women with low milk supply, (13, 14) one of the most commonly reported reasons that women stop breastfeeding (15). Such traits would not be expected to persist in the population if breastfeeding were the only option available to the women who expressed them.

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 to be perceived. A 2008 study analyzed 20 studies conducted in communities around the world: of women who wean early, an average of 35% reported perception of low milk supply as the primary reason. This simplistic explanation for low milk supply can be harmful to mothers and babies as it is accompanied by pressure for a mother to override her perceptions about her own body and the needs of her infant.

The identification of genetic markers associated with low milk supply supports a physiological explanation that will not be overcome by interventions that target a mother’s perception. In an upcoming post, we will explore the issue of low milk supply and discuss the vital importance of trusting mothers to recognize when the needs of their babies are not being met.

References

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. https://www.worldwildlife.org/stories/meet-the-biggest-animal-in-the-world#:~:text=The%20Antarctic%20blue%20whale%20(Balaenoptera,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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