Lack of functional alpha-lactalbumin prevents involution in Cape fur seals and identifies the protein as an apoptotic milk factor in mammary gland involution

Julie A Sharp,Christophe Lefèvre,Kevin R Nicholas

doi:10.1186/1741-7007-6-48

Julie A Sharp, Christophe Lefèvre + Show 1 more

Open Access

https://doi.org/10.1186/1741-7007-6-48

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Abstract

BackgroundThe mammary gland undergoes a sophisticated programme of developmental changes during pregnancy/lactation. However, little is known about processes involving initiation of apoptosis at involution following weaning. We used fur seals as models to study the molecular process of involution as these animals display a unique mammary gland phenotype. Fur seals have long lactation periods whereby mothers cycle between secreting copious quantities of milk for 2 to 3 days suckling pups on land, with trips to sea alone to forage for up to 23 days during which time mammary glands remain active without initiating apoptosis/involution.ResultsWe show the molecular basis by which alpha-lactalbumin (LALBA), a secreted milk protein, is absent in Cape fur seals and demonstrate an apoptotic function for LALBA when exposed to mammary cells.ConclusionWe propose that apoptosis does not occur in fur seal mammary glands due to lack of LALBA in fur seal milk, allowing evasion of involution during a foraging trip. Our work identifies LALBA as a milk factor that feeds back on the mammary gland to regulate involution.

Highlights

The mammary gland undergoes a sophisticated programme of developmental changes during pregnancy/lactation
LALBA gene expression in the fur seal mammary gland Affymetrix canine arrays were used to examine the pattern of gene expression in mammary tissue from Cape fur seals (Arctocephalus pusillus) during pregnancy, on-shore lactation and off-shore lactation
Using this approach candidate apoptosis genes were examined for significant differences in expression, and unusually low levels of a major milk protein gene, LALBA, were observed in mammary glands of lactating Cape fur seals

Summary

Introduction

The mammary gland undergoes a sophisticated programme of developmental changes during pregnancy/lactation. We used fur seals as models to study the molecular process of involution as these animals display a unique mammary gland phenotype. Fur seals have long lactation periods whereby mothers cycle between secreting copious quantities of milk for 2 to 3 days suckling pups on land, with trips to sea alone to forage for up to 23 days during which time mammary glands remain active without initiating apoptosis/involution. The massive changes of form and function of mammary glands over the life span of a female are characterized by extreme changes in cell proliferation, differentiation, secretion and death, which accompanies pregnancy, lactation and involution upon weaning. Upon milk stasis, due to absence of sucking at weaning, the mammary gland regresses and is remodelled by a process known as involution, which cleanses the gland and returns it to a virgin-like state.

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