Mutations in a protein that transports zinc to specific tissues in the body—including mammary glands—may be a reason that some women have difficulty breastfeeding.
It has long been known that zinc, an essential trace element, is passed to infants through mother’s breast milk.
The levels of zinc in mother’s milk and the effects of zinc deficiency in infants have been previously studied, but the role of zinc in breast development and function in lactating mothers is a relatively new area of research.
The breast milk of women with a mutation in the ZnT2 protein has very low amounts of zinc, which can in turn cause severe zinc deficiency in exclusively breast-fed infants.
New research with mice suggests that ZnT2 mutations may also cause other deficiencies in breast milk and may create difficulty for breastfeeding in general.
“This finding changes the paradigm,” says Shannon L. Kelleher, associate professor of cellular and molecular physiology at Penn State College of Medicine. “It is no longer only about transporting zinc into milk, but now it’s also about milk composition and milk production.”
For the new study, published in Journal of Biological Chemistry, researchers studied the function of ZnT2 by observing the development of mammary glands in mice—both with and without functioning.
The group of mice lacking ZnT2 showed reduced mammary gland development and severe defects in function during lactation.
Breastfeeding is hard
ZnT2 transports zinc by importing it into vesicles, small organelles within the cell, that then secrete zinc into the breast milk. Zinc is also necessary to trigger the growth of mammary glands, mammary epithelial cells, and secretion pathways. Without functional ZnT2, zinc accumulates in the cytoplasm, becoming toxic to the cell.
“It is believed that ‘breast is best,’ but breastfeeding is hard to do,” says Kelleher, adding that breast-feeding isn’t instinctive, but is a learned behavior.
“We believe that there is biology behind some breast-feeding issues. If we can identify women who will have trouble with breastfeeding while they’re still pregnant (by identifying mutations in their ZnT2 proteins), then maybe we can help them better prepare before the baby comes.”
If zinc is not transported by ZnT2, its absence impacts milk composition and volume. Along with insufficient zinc levels in breast milk, mice without ZnT2 had significantly reduced beta-casein, fat, and lactose in their milk. All are important for sustaining infant health. These mice were also unable to produce an adequate volume of milk for their offspring.
“We really need to better understand the biological factors of lactation,” Kelleher says. “Seventy-five percent of mothers intend to breast-feed when they leave the hospital. Six months later, only 14 percent are still exclusively breast-feeding.”
In the future, Kelleher hopes to sequence the gene that codes for ZnT2 in women to figure out how lactation is affected and how to help pregnant and lactating women who have ZnT2 mutations.
Other researches from Penn State and from the US Army Research Institute of Environmental Medicine, RIKEN Center for Integrative Medical Sciences, and Suzuka University of Medical Science contributed to the study.
The National Institutes of Health and the Penn State College of Medicine department of surgery supported the work.
Source: Penn State