Terminal differentiation of goat mammary tissue during pregnancy requires the expression of genes involved in immune functions

Abstract

Terminal differentiation of mammary tissue into a functional epithelium that synthesizes and secretes milk occurs during pregnancy. The molecular mechanisms underlying this complex process are poorly understood, especially in ruminants. To obtain an overview of the ruminant mammary gland's final differentiation process, we conducted time-course gene expression analysis of five physiological stages: four during pregnancy (P46, P70, P90, and P110) and one after 40 days of lactation (L40). An appropriate loop experimental design was used to follow gene expression profiles. Using three nulliparous (pregnancy) or primiparous (lactation) goats per stage, we performed a comparison starting from nine dye-swaps and using a 22K bovine oligoarray. Statistical analysis revealed that the expression of 1,696 genes varied significantly at least once in the study. These genes fell into 19 clusters based on their expression profiles. Identification of biological functions with Ingenuity Pathway Analysis software revealed several similarities, in keeping with physiological stages described in mice. As in mice, expression of milk protein genes began at midpregnancy, and genes regulating lipid biosynthesis were induced at the onset of lactation. During the first half of pregnancy, the molecular signature of goat mammary tissue was characterized by the expression of genes associated with tissue remodeling and differentiation, while the second half was mainly characterized by the presence of messengers encoding genes involved in cell proliferation. A large number of immune-related genes were also induced, supporting recent speculation that mammary tissue has an original immune function, and the recruitment of migrating hematopoietic cells possibly involved in the branching morphogenesis of the mammary gland. These data hint that the induction of differentiation occurs early in pregnancy, very likely before P46. This period is therefore crucial for obtaining a healthy and productive mammary gland.

Milk Protein Synthesis in the Lactating Mammary Gland: Insights from Transcriptomics Analyses

“…In Figure 1 are reported the temporal patterns of transcription of caseins, alpha-lactalbumin, whey acid protein, and albumin from pregnancy to lactation in two ruminant species (dairy cow [89] and dairy goat [90]), two monogastric species (mouse [91] and pig [92]), and a marsupial (kangaroo; Macropus eugenii [93]). Those were the only microarray datasets publicly available at the time of this writing.…”

“…Temporal expression pattern of genes encoding casein alpha-S1, casein alpha-S2 (for mouse the genes are casein alpha s2-like A and casein alpha s2-like B), casein beta, casein kappa (CSN1S1, CSN1S2-(a) and (b) for mouse -, CSN2, and CSN3, respectively), alpha-lactalbumin (LALBA) and albumin (ALB) in dairy cows [89], mouse [91], pig [92], goat [90], and kangaroo (Macropus eugenii; [93]). Dataset, except for dairy cows and kangaroo, was obtained through NCBI Gene Expression Omnibus (GEO at http://www.ncbi.nlm.nih.gov/geo/): GSE14008 for goat, GSE4222 for mouse, and GSE30704 for pig.…”

“…Temporal expression of genes coding for major proteins found in whey protein concentrate (WPC; upper panels) and in the buttermilk protein concentrate (BMP; lower panels) [83]. Data are for Holstein dairy cows [89], Saanen or Alpine goats [90], FVB mice [91] and Large white sows [92]. Data were recovered and treated as reported in the legend for Figure 1.…”

Biosynthesis of milk fat, protein, and lactose: roles of transcriptional and posttranscriptional regulation

“…The use of large transcriptomic analysis (i.e., microarray or RNA sequencing) by which to study the adaptation of mammary gland to lactation and/or change in milk production under specific conditions has been carried out in mouse (4,54,122,123,143,189,191,217,236,256), rat (3,47,187), bovine (31,36,56,75,96,144,183,209,218,233,239), sheep (209), goat (71,163,164), human (121,139,147), pig (204), kangaroo (120), and seal (144). It is beyond the scope of the current review to present a thorough discussion of the results from those studies.…”

Gene Expression During Early Folliculogenesis in Goats Using Microarray Analysis1

“…However, cross-species microarray hybridization using available genome tools for a closely related model organism, e.g., bovine genome arrays, has enabled new findings in goats. The success of applying bovine genome arrays to goats [19,20] provides a new alternative for studying gene expression in a whole-genome scale. Currently there are no studies of gene expression during the development of ovarian follicles in goats.…”