Introduction
Human milk is considered the best source of nutrition for infants, and it provides numerous benefits for both mother and child. Even though breastfeeding is the most natural way to feed infants, a lot of mothers these days express difficulty with the process. Along with environmental factors like maternal nutrition status, partner support, stress, and the baby's latching ability that may affect lactation outcomes, intrinsic factors like maternal genetics may also impact the quantity and quality of human milk produced. Genetic factors which can affect the growth and development of infants are currently being studied. Even though nutrient-deficient human milk cases are rare, some ethnic groups have more genetic differences that alter the composition of human milk. As a result, these genetic variations should be given more consideration for diagnosis and, if necessary, treatment.
What Are the Hormones That Induce the Production of Human Milk?
Mammary glands undergo various changes throughout the life of a woman. Estrogen hormones start the development of mammary glands when a girl reaches puberty. During pregnancy, increased progesterone and prolactin levels start the mammary gland's alveolar development and the proliferation of its epithelial cells. The differentiation of mammary epithelial-secreting cells, which can synthesize and secrete particular milk components, depends on the lactogenic hormones estrogen, progesterone, prolactin, and metabolic hormones like insulin.
"Secretion activation" refers to the stage after birth when hormonal adjustments cause mammary gland epithelial cells to start secreting milk. Progesterone levels drop sharply in this stage, and prolactin, insulin, and cortisol are necessary to control this critical phase.
Additionally, the posterior pituitary releases oxytocin, a neuropeptide hormone of nine amino acids that is synthesized in the brain, into the bloodstream to act as a cue for infants to suckle their mothers' nipples. As a result of oxytocin's activation of contraction in the mammary gland's myoepithelial cells, milk is ejected, or the "let-down" reflex releases milk from the ducts.
Which Genetic Variations Affect the Composition of Human Milk?
Recently, variations in some genetic factors were found to affect the composition of breast milk in addition to other factors like nutrition and hormone regulation of the mother.
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Transient newborn zinc deficit (TNZD), a condition that causes severe zinc insufficiency only in breastfed infants, has been linked to a mutation in the SLC30A2/ZnT2 gene. Since the publication of this ground-breaking study, at least ten different SLC30A2/ZnT2 mutations have been discovered in mothers whose milk contained low levels of zinc and, consequently, in the blood of their breastfed babies who suffered from severe zinc deficiency. This condition was known as TNZD because zinc supplementation for the infants during nursing healed their symptoms of zinc insufficiency, and weaning completely cured them.
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Breast cancer resistance protein (BCRP/ABCG2), an ATP-driven (adenosine triphosphate) multidrug efflux transporter, has been linked to a substantial induction of gene expression in the mammary gland during pregnancy and lactation in mice, cows, and humans. A 63-fold fall in riboflavin (vitamin B2) concentration and a 3-fold reduction in biotin levels were seen in mice with knock-out of BCRP1.
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Iodine intake from human milk is essential for the creation of thyroid hormones that contain iodine and, as a result, for newborns' normal cognitive and physical development. Thyroid hormones, in particular, are necessary for healthy brain growth. It has been noted that iodine supplementation or the use of iodized salt can raise the iodine concentration in human milk, which is dependent on the iodine status of the mother. When compared to its plasma levels, iodine concentration in human milk is 20–50 times higher.
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For infants, choline is a crucial nutrient because it is necessary for their quick growth and development. Various physiological processes require choline to function. Choline, for instance, is a key lipid in membranes and is a component of the neurotransmitter acetylcholine as well as the phospholipid phosphatidylcholine.
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Docosahexaenoic acid (DHA) is produced by fatty acid desaturases (FADS), which are encoded by the genes FADS1 and FADS2, from -linolenic acid. Dietary sources of DHA include fish and fish oil. The genotype of the FADS1 and FADS2 gene clusters was shown to affect the fatty acids in human milk.
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The typical differences in the protein composition of human milk have been attributed to SNPs (Single nucleotide polymorphism). However, very little is known about nucleotide variation and protein content in humans. This phenomenon was better understood in dairy animals, where SNPs in the bovine casein locus were discovered to be related to milk yield and milk protein concentration.
Which Genetic Variations Affect the Supply of Human Milk?
Familial alactogenesis is caused by a mutation in the LoF (Loss of function) gene that causes premature translation termination and a significant reduction in the gene's mRNA (messenger ribonucleic acid) through nonsense-mediated RNA decay. In this family, the detected LoF mutation in PRL (Prolactin gene) was also linked to infertility, proving that infertile women are more likely to experience breastfeeding challenges and need extra care and assistance to breastfeed successfully.
Three sisters with familial hyperprolactinemia have been reported to have a heterozygous LoF mutation (p.His188Arg) in PRLR (Prolactin receptor). Prolactin levels greater than usual indicate hyperprolactinemia, which is caused by tumors in 50 % of cases. In this example, one sister, who was between the ages of 18 and 31, had four pregnancies that were successful with lactation and were given dopamine agonist therapy to end persistent galactorrhea (a condition where milk or milk-like), whereas the other two sisters experienced oligomenorrhea (irregular periods or large gap between menstrual cycles) and infertility. The variations in phenotypes between these sisters may be explained by the late onset of post-pubertal hyperprolactinemia. However, the heterozygous LoF mutation in PRLR carried by one of these sisters who were successful in nursing her offspring suggests that the latter mutation did not always hinder or abrogate lactation outcomes.
Conclusion
Human milk comprises various nutrients, antibodies, immune cells, and other components. Various factors, such as nutrition, diet, lifestyle, age, body type, etc., can affect breast milk's composition. However, recent studies suggest that even the mother's genetic factors can impact milk composition and production and supply of milk. Hence various components can alter the components of breast milk.
