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UNSW Embryology

Normal Development - Milk

© Dr Mark Hill (2011)

Acknowledgements

Introduction

Breast milk makes us mammals! This current page discusses the issues related to milk.

The review article (abstract shown below) by Goldman in 2000 may provide a way of thinking about GIT and human milk.

See also system development notes Integumentary Development - Mammary Glands.

Page Links: Introduction | Some Recent Findings | Milk Composition | Human Milk | Milk Production | Materal Environmental Components | References | Glossary

Some Recent Findings

Asensi MT, Martinez-Costa C, Buesa J. Anti-rotavirus Antibodies in Human Milk: Quantification and Neutralizing Activity. J Pediatr Gastroenterol Nutr. 2006 May;42(5):560-567. "Anti-rotavirus antibodies are only partly responsible for the neutralizing activity detected in milk and serum. This result suggests that other components possessing suppressive activity against rotavirus must also be present."

Kent JC. How breastfeeding works. J Midwifery Womens Health. 2007 Nov-Dec;52(6):564-70. Review.

Milk Composition

Most mammals produce milk containing similar components which may occur at different concentrations. Composition of the maternal diet can affect the concentration of some of these components. In addition, some materal environmental components can also appear in the milk.

Typical secreted milk contains:

Carbohydrate: lactose, glucose, galactose, and oligosaccharides

Electrolytes

Fats: triglycerides and fatty acids (omega-3 polyunsaturated fatty acids, such as docosahexanoic acid)

Minerals

Proteins: caseins, alpha-lactalbumin, immunoglobulins, albumin, lactoferrin, nonprotein nitrogen, enzymes, hormones, growth factors, and nucleotides

Trace elements: selenium and iodine

Vitamins: A, B1 (thiamin), B2 (riboflavin), B5 (pantothenic acid), B6 (pyridoxine), B12 (cobalamin), D, and E

Water

Materal Environmental Components

Some materal environmental components (contaminants) can also appear in the milk.

Lead: Gulson BL, Jameson CW, Mahaffey KR, Mizon KJ, Patison N, Law AJ, Korsch MJ, Salter MA. Relationships of lead in breast milk to lead in blood, urine, and diet of the infant and mother. Environ Health Perspect. 1998 Oct;106(10):667-74.

"The levels of lead in breast milk are thus similar to those in plasma. Breast-fed infants are only at risk if the mother is exposed to high concentrations of contaminants either from endogenous sources such as the skeleton or exogenous sources."

Organic Pollutants: Tanabe S, Kunisue T. Persistent organic pollutants in human breast milk from Asian countries. Environ Pollut. 2007 Mar;146(2):400-13. Epub 2006 Sep 1. Review.

polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs), hexachlorobenzene (HCB)

Human Milk

"Human milk contains agents that affect the growth, development and functions of the epithelium, immune system or nervous system of the gastrointestinal tract. Some human and animal studies indicate that human milk affects the growth of intestinal villi, the development of intestinal disaccharidases, the permeability of the gastrointestinal tract and resistance to certain inflammatory/immune-mediated diseases. Moreover, one cytokine in human milk, interleukin (IL)-10, protects infant mice genetically deficient in IL-10 against an enterocolitis that resembles necrotizing enterocolitis (NEC) in human premature infants.

There are seven overlapping evolutionary strategies regarding the relationships between the functions of the mammary gland and the infant’s gastrointestinal tract as follows:

  1. certain immunologic agents in human milk compensate directly for developmental delays in those same agents in the recipient infant
  2. other agents in human milk do not compensate directly for developmental delays in the production of those same agents, but nevertheless protect the recipient
  3. agents in human milk enhance functions that are poorly expressed in the recipient
  4. agents in human milk change the physiologic state of the intestines from one adapted to intrauterine life to one suited to extrauterine life
  5. some agents in human milk prevent inflammation in the recipient’s gastrointestinal tract
  6. survival of human milk agents in the gastrointestinal tract is enhanced because of delayed production of pancreatic proteases and gastric acid by newborn infants, antiproteases and inhibitors of gastric acid production in human milk, inherent resistance of some human milk agents to proteolysis, and protective binding of other factors in human milk
  7. growth factors in human milk aid in establishing a commensal enteric microflora"

(Text from: Goldman AS. Modulation of the gastrointestinal tract of infants by human milk. Interfaces and interactions. An evolutionary perspective. J Nutr. 2000 Feb;130(2S Suppl):426S-431S. Review.)

Milk Production

Development of the breasts and milk production is mainly regulated by the anterior pituitary hormone prolactin (PRL). The release of prolactin is regulated by the hypothalamus prolactin-releasing hormone (PRLH, prolactin-releasing peptide, PRRP)

Prolactin worms model
Prolactin Space fill model

Molecular models of prolactin protein structure.

(More? Teilum etal, 2005)

Prolactin hormone other roles include:

regulating follicle stimulating hormone (FSH) effect on the ovary.

increased maternal myelination processes during pregnancy.

Prolactin-releasing hormone (PRLH, prolactin-releasing peptide, PRRP) is an 87 amino acid peptide hypothalamus hormone which regulates anterior pituitary release of prolactin.

Prolactin signaling Pathway

In the mammary gland:

1. Prolactin binds to its receptor (PRLR) and causes them to dimerize.

2. Receptor-associated tyrosine kinase Jak2 phosphorylates: the prolactin receptor and Stat5a and Stat5b (signal transducers and activators of transcription).

3. Activated Stat5a and -5b are transported into the nucleus

4. They specifically bind DNA of target genes (the GAS sequence, TTCNNNGAA).

5. Induce transcription that promote: proliferation, differentiation, and lactogenesis.

Galactorrhoea is the inappropriate production of milk that is often associated with anterior pituitary tumours producing excess prolactin. This condition can occur in both females and males.

Links: Endocrine Development - Pituitary | Endocrine Development - Hypothalamus | Integumentary Development - Mammary Glands | OMIM - PRL | OMIM - PRLH

References: Teilum K, Hoch JC, Goffin V, Kinet S, Martial JA, Kragelund BB. Solution structure of human prolactin. J Mol Biol. 2005 Aug 26;351(4):810-23.

References

Links: Reviews | Articles | Online Textbooks | Search Textbooks | Search PubMed | Glossary

PubMed

Kent JC. How breastfeeding works. J Midwifery Womens Health. 2007 Nov-Dec;52(6):564-70. Review.

Oddy WH. The impact of breastmilk on infant and child health. Breastfeed Rev. 2002 Nov;10(3):5-18. Review

Field CJ. The immunological components of human milk and their effect on immune development in infants. J Nutr. 2005 Jan;135(1):1-4. Review.

Preterm Baby Nutrition

Klein CJ. Nutrient requirements for preterm infant formulas. J Nutr. 2002 Jun;132(6 Suppl 1):1395S-577S. Review.

Marriott LD, Foote KD. Advances in the nutrition of preterm infants. J R Soc Health. 2003 Sep;123(3):159-64. Review.

Its not just about Baby Nutrition

Zadik Z. Maternal nutrition, fetal weight, body composition and disease in later life. J Endocrinol Invest. 2003 Sep;26(9):941-5. Review.

Those helpful bacteria

Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. 2005 Mar 25;307(5717):1915-20. Review.

Hooper LV, Midtvedt T, Gordon JI. How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annu Rev Nutr. 2002;22:283-307. Epub 2002 Apr 4. Review.

Kaper JB, Sperandio V. Bacterial cell-to-cell signaling in the gastrointestinal tract. Infect Immun. 2005 Jun;73(6):3197-209. Review.

Changes

Veereman-Wauters G. Neonatal gut development and postnatal adaptation. Eur J Pediatr. 1996 Aug;155(8):627-32. Review.

de Santa Barbara P, van den Brink GR, Roberts DJ. Development and differentiation of the intestinal epithelium. Cell Mol Life Sci. 2003 Jul;60(7):1322-32. Review.

Your gut has an endocrine function

Lee CS, Kaestner KH. Clinical endocrinology and metabolism. Development of gut endocrine cells. Best Pract Res Clin Endocrinol Metab. 2004 Dec;18(4):453-62. Review.

Articles

Asensi MT, Martinez-Costa C, Buesa J. Anti-rotavirus Antibodies in Human Milk: Quantification and Neutralizing Activity. J Pediatr Gastroenterol Nutr. 2006 May;42(5):560-567. Teilum K, Hoch JC, Goffin V, Kinet S, Martial JA, Kragelund BB. Solution structure of human prolactin. J Mol Biol. 2005 Aug 26;351(4):810-23.

Search PubMed

Search May 2006 "lactation" 48,729 reference articles of which 4,376 were reviews.

Search PubMed: lactation | human milk | milk | breast feeding |

WWW Links

Australia ABC - Diet and nutrition

New Zealand Medsafe - Drug Safety in Lactation

USA American Society for Nutritional Sciences

WHO WHO Nutrition

Glossary of Terms

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