Go with the flow-biology and genetics of the lactation cycle

Abstract

Lactation is a dynamic process, which evolved to meet dietary demands of growing offspring. At the same time, the mother's metabolism changes to meet the high requirements of nutrient supply to the offspring. Through strong artificial selection, the strain of milk production on dairy cows is often associated with impaired health and fertility. This led to the incorporation of functional traits into breeding aims to counteract this negative association. Potentially, distributing the total quantity of milk per lactation cycle more equally over time could reduce the peak of physiological strain and improve health and fertility. During lactation many factors affect the production of milk: food intake; digestion, absorption, and transportation of nutrients; blood glucose levels; activity of cells in the mammary gland, liver, and adipose tissue; synthesis of proteins and fat in the secretory cells; and the metabolic and regulatory pathways that provide fatty acids, amino acids, and carbohydrates. Whilst the endocrine regulation and physiology of the dynamic process of milk production seems to be understood, the genetics that underlie these dynamics are still to be uncovered. Modeling of longitudinal traits and estimating the change in additive genetic variation over time has shown that the genetic contribution to the expression of a trait depends on the considered time-point. Such time-dependent studies could contribute to the discovery of missing heritability. Only very few studies have estimated exact gene and marker effects at different time-points during lactation. The most prominent gene affecting milk yield and milk fat, DGAT1, exhibits its main effects after peak production, whilst the casein genes have larger effects in early lactation. Understanding the physiological dynamics and elucidating the time-dependent genetic effects behind dynamically expressed traits will contribute to selection decisions to further improve productive and healthy breeding populations.

Keywords: breeding value; genome-wide association; genomic prediction; genomic selection; lactation curve; longitudinal; time-dependent.

Figure 1

(A) Milk production and (B) energy supply and requirements during the lactation cycle of 340 days. (A) The curve represents the milk yield per day of lactation and reaches a peak production around lactation days 40–50. Shortly before lactation and until peak production the udder and the alveolar system are highly developed. In later lactation the alveolar system regresses continuously until the end of lactation and into involution. (B) The blue curve represents the energy that is needed for milk production and maintenance of vital body functions. The energy needed for milk production is highest when milk production reaches a peak. At the same time the energy taken in through food (purple curve) cannot cover the energy requirements for milk production which leads to a loss in body energy stores (black curve). This imbalance in energy homeostasis changes with the decline of milk production in late lactation.

Figure 2

The process of milk secretion in the udder of a cow (partially adapted from Wattiaux, 1996). Milk is secreted in the alveoli system of the mammary gland. Several substances can pass the cell membrane from the blood stream (water, minerals, vitamins, immune-globulins), whilst others need transporters and are produced in the secretory cells (proteins, fat, lactose).

Figure 3

Chronology of gene expression and physiological processes during a lactation cycle. DIM, days in milk.

Figure 4

Simplified pathways for major genes involved in milk production. Green boxes are genes, orange circles are the pathways the genes are involved in, blue boxes are the milk production traits that are affected (information is assembled from KEGG Pathway Database, 17.11.2014; http://www.genome.jp/kegg/pathway.html and literature review; for gene names, see Table 1).