Impacts of prenatal nutrition on animal production and performance: a focus on growth and metabolic and endocrine function in sheep

Abstract

The concept of foetal programming (FP) originated from human epidemiological studies, where foetal life nutrition was linked to health and disease status later in life. Since the proposal of this phenomenon, it has been evaluated in various animal models to gain further insights into the mechanisms underlying the foetal origins of health and disease in humans. In FP research, the sheep has been quite extensively used as a model for humans. In this paper we will review findings mainly from our Copenhagen sheep model, on the implications of late gestation malnutrition for growth, development, and metabolic and endocrine functions later in life, and discuss how these implications may depend on the diet fed to the animal in early postnatal life. Our results have indicated that negative implications of foetal malnutrition, both as a result of overnutrition and, particularly, late gestation undernutrition, can impair a wide range of endocrine functions regulating growth and presumably also reproductive traits. These implications are not readily observable early in postnatal life, but are increasingly manifested as the animal approaches adulthood. No intervention or cure is known that can reverse this programming in postnatal life. Our findings suggest that close to normal growth and slaughter results can be obtained at least until puberty in animals which have undergone adverse programming in foetal life, but manifestation of programming effects becomes increasingly evident in adult animals. Due to the risk of transfer of the adverse programming effects to future generations, it is therefore recommended that animals that are suspected to have undergone adverse FP are not used for reproduction. Unfortunately, no reliable biomarkers have as yet been identified that allow accurate identification of adversely programmed offspring at birth, except for very low or high birth weights, and, in pigs, characteristic changes in head shape (dolphin head). Future efforts should be therefore dedicated to identify reliable biomarkers and evaluate their effectiveness for alleviation/reversal of the adverse programming in postnatal life. Our sheep studies have shown that the adverse impacts of an extreme, high-fat diet in early postnatal life, but not prenatal undernutrition, can be largely reversed by dietary correction later in life. Thus, birth (at term) appears to be a critical set point for permanent programming in animals born precocial, such as sheep. Appropriate attention to the nutrition of the late pregnant dam should therefore be a priority in animal production systems.

Keywords: Adipose tissue; Endocrine function; Foetal programming; Metabolic function; Sheep.

Fig. 1

The experimental design of the Copenhagen sheep model showing different nutritional and dietary interventions during late gestation and early postnatal life in sheep (obtained from Khanal et al., 2014 [10]). Late gestational nutrition groups: HIGH, fulfilling 150% of Danish requirements for energy and 110% of requirements for protein; LOW, fulfilling only 50% of requirements for energy and protein; NORM; fulfilling 100% requirements for energy and protein. Early postnatal (from 3 d after birth until 6 mo of age) nutrition groups: one lamb from each twin pair was allocated to a HCHF diet (high-starch-high fat consisting of a milk replacer-dairy cream mix supplemented with rolled maize), and the other was fed a CONV (conventional/moderate, hay-based diet; growth rate of appr. 225 g/d) diet

Fig. 2

Impacts of late gestational over- and undernutrition on fat deposition patterns in adolescent (6 months old) offspring (left panel: subcutaneous to mesenteric fat ratio; right panel: subcutaneous to perirenal fat ratio) (obtained from Khanal et al. [10]). For HIGH, NORM and LOW, see legends for Fig. 1

Fig. 3

Morphology of Van Gieson-stained subcutaneous adipose tissue from 6 months old adolescent lambs and 2 years old adult sheep (obtained from Nielsen et al. [39]). Panel A: examples of pictures from the 4 groups of lambs, used to grade cell size (and with negligible collagen infiltration) showing a larger population of very small cells in the LOW/CONV group (bottom left) relative to the other groups, and extensive hypertrophy in adipocytes from HCHF lambs (pictures to the right). Panel B: morphological characteristics observed in slides from adult LOW sheep, which was not restricted to a specific early postnatal diet (pictures at the top) with extensive collagen infiltration (grade 4), which was never observed to the same extent among NORM sheep (max grade assigned = 2). For HIGH, NORM, LOW, CONV, HCHF see legends for Fig. 1

Fig. 4

Impacts of late gestational nutrition on hyperplasia and hypertrophy of different adipose tissue depots in adolescent (6 months old) offspring (obtained from Khanal et al., unpublished data). SF, subcutaneous fat (encircled as green); MF, mesenteric fat (encircled as yellow); PRF, perirenal fat (encircled as red). For HIGH, NORM and LOW, see legends for Fig. 1. Each hexagonal structure represents an individual adipocyte

Fig. 5:

Impacts on early life nutrition on animal physiology and metabolism.