Does maternal size, nutrition and metabolic status affect offspring production traits in domestic species?

The Developmental Origins of health and Disease state that environmental conditions during pregnancy affect long term outcomes in offspring. In the present paper, effects of maternal size and breed as well as maternal nutrition on offspring size, growth and production traits are described. Although birthweight is mostly not affected, metabolic perturbations are often observed in adult offspring. In animal production, however, the relation between developmental conditions and long-term offspring outcome may remain unnoticed. Nevertheless, improving dams' health and nutrition before and during pregnancy may help improving production traits in domestic animals.


Introduction
In mammals, developmental conditions at the time of conception, during pregnancy and the neonatal period are known to affect long-term post-natal health, as known under the term "Developmental Origins of Health and Disease" (DOHaD).This phenomenon, is associated with modifications in gene expression due to environmentally induced epigenetic mechanisms.Maternal environment, such as maternal metabolism and nutrition, or the use of reproductive biotechnologies, may have an effect on feto-placental development, growth and subsequent adult health, thus affecting offspring performance and longevity.
This article aims to summarize existing knowledge on long term effects of maternal phenotype in domestic species and their potential impact on animal health, fertility and welfare.Future directions both in research and for improvement of field management are discussed.

The other side of genetics: effect of maternal phenotype/genotype
Genetic selection for production traits is the basis of animal breeding.Taking into consideration maternal genetic value and production, the sire is selected based on his genetic indices and heritability, in order to improve desired production traits.Maternal genotype and phenotype are also seminal in determining the environment in which the embryo and fetus will develop, regardless of production traits.This can be studied by comparing cross-bred offspring born to dams of different genotypes, or by studying phenotypic variation in genetically identical animals (Fig. 1).
In pigs, the cross-breeding between Meishan sows (200 kg adult weight) and Yorkshire males (300 kg adult weight) yields lighter piglets than the opposite crossing (Meishan males and Yorkshire sows; Biensen et al., 1999).Similarly, in cattle, calves born to South Devon cows (790 kg adult weight) and Dexter bulls (340 kg adult weight) were approximately 6 kg heavier than crossbred calves born to a Dexter cow (Joubert and Hamond, 1958).Moreover, Charolais breed embryos transferred into Brahman cows are lighter at birth (mean 29 kg) compared to Charolais embryos transferred into Charolais recipients (mean 63 kg).Inversely, Brahman embryos transferred into Charolais recipients result in calves with heavier birthweight (mean 41 kg) than those produced by the transfer of Brahman embryos into Brahman cows (mean 19 kg;Ferrell, 1991).These results indicate that maternal breed and consequently maternal size and environment will affect offspring weight and size at birth, regardless of genetic potential.
Further consequences on postnatal development have been explored in horses.In the first half of the 20th century, Walton and Hammond elegantly demonstrated, using cross-breeding between large Shire horses and small Shetland ponies, that crossbred offspring whose dam was a Shetland pony were smaller at birth and remained smaller as adults than those whose dam was a Shire mare (Walton and Hammond, 1938).Almost 50 years later, Tischner et al. showed that Polish pony embryos transferred into draft mares produced foals that were larger at birth and remained larger as adults, compared to those that had been transferred into mares of their own breed (Tischner et al., 2000).More recently, the transfer of pony embryos into mares of larger breeds was shown to consistently increase fetal and postnatal growth until adulthood.Conversely, foals from a larger breed born to pony mares were small at birth and only partially caught-up to controls of the same breed (Allen et al., 2004;Peugnet et al., 2014).Moreover, both excess and reduced fetal growth were associated with osteoarticular lesions and metabolic perturbations, some of which still present at 2 years of age (Peugnet et al., 2014(Peugnet et al., , 2016)).

Effect of maternal nutrition
Procedures in terms of maternal nutrition in domestic animals vary greatly depending on breed, location, availability of feedstuff and season, amongst other factors.The choice of dietary treatments in experimental protocols is also very diverse, rendering it difficult to draw clear conclusions.In general, the effects of maternal nutrition on offspring phenotype are marginal, except when dietary treatments are severe and prolonged as reviewed recently (Funston et al., 2012;Chavatte-Palmer et al., 2015, 2016;Sinclair et al., 2016;Opsomer et al., 2017).The list of studies presented here does not claim to be exhaustive as the authors have selected key examples to illustrate each nutritional condition.

Excess nutrition and obesity
In many studies, excess nutritional intake during pregnancy is confounded with maternal obesity.Obesity can be defined as excess adiposity above a certain level as defined by the authors depending on studies, before breeding and during pregnancy.Here we tried to discriminate studies with maternal gestational overfeeding from studies with maternal obesity prior to breeding.
Effects of excess maternal nutrition have been mainly studied in sheep (Table 1) with little observed effects on lamb birthweight and postnatal growth (Hoffman et al., 2014;Khanal et al., 2014;Kleemann et al., 2015;Sen et al., 2016).Nevertheless, expression of Insulin Growth Factor 1 (IGF1) is increased in the lamb liver (Hoffman et al., 2014) resulting in increased plasma IGF1 concentrations (Hoffman et al., 2016) and lipid accumulation is also observed in the lambs' muscle (Hoffman et al., 2014;Reed et al., 2014), together with increased insulin resistance (Hoffman et al., 2016), increased adiposity (Khanal et al., 2014), hyperglycemia and alteration of hepatic signaling pathways (Philp et al., 2008).Finally, increased ovarian size and reduced ovarian follicular numbers have also been observed (Da Silva et al., 2003;Kleemann et al., 2015).Ad libitum access to feedstuff at adulthood (19-22 months) increased food intake, weight gain, visceral and subcutaneous fat, basal glycemia and insulinemia in all animals but offspring born to obese dams were less affected than offspring born to control dams (Long et al., 2010(Long et al., , 2015)).
When maternal obesity was induced by overfeeding dams starting 2 months before breeding and until lambing, offspring birthweight was not affected but glucose metabolism was consistently and durably altered.The number of pancreatic β-cells was reduced in fetal life, resulting in hyperglycemia, un hypoinsulinemia and reduced pancreatic weight at birth and increased insulin resistance and altered glycemic regulation in adults.Moreover, muscular fibrosis and hyperleptinemia were observed (Long et al., 2010(Long et al., , 2015;;Huang et al., 2012;Zhang et al., 2012).In order to understand the importance of preconceptional obesity, embryos produced in adult obese or control ewes were transferred in adolescent control or obese ewes (Wallace et al., 2017).Pregnancy length was shorter in obese recipients and resulted in reduced lamb birthweight compared to controls, regardless of donor group.The colostrum quality was also affected by obesity (Wallace et al., 2017).Finally, in cattle, feeding with 125% requirements from 3 months of gestation increases calf birthweight but weaning weight and carcass quality at 5 months of age were not different between groups (Wilson et al., 2016).Thus, excess maternal nutrition and maternal obesity both affect lipid and glucose metabolism in offspring and may also alter body composition and muscle quality.
In goats, a progressive maternal undernutrition (goats were fed 50 to 80% of the spontaneous intake of controls) in the last third of gestation reduced birthweight in male kids only although Non-esterified fatty Acid concentrations (NEFA) were increased in all kids (Laporte-Broux et al., 2011).Subsequently at 1 and 2 years of age, restricted female offspring ate more than controls but no difference in energy metabolism was evidenced between groups (Laporte-Broux et al., 2012).
In beef cattle, feeding cows at 80% requirements between 3 and 6 months of gestation reduced subcutaneous rib fat thickness and increased the intra-to inter-muscular fat ratio in 7 months old calves (Mohrhauser et al., 2015).The birthweight of calves born to Angus cross-bred cows fed 60% of their requirements between 30 and 85 days or between 30 and 140 days of gestation was the same as offspring born to cows fed 100% of requirements but their liver was heavier (Prezotto et al., 2016).Moreover, nutritional supplementation of restricted beef heifers during pregnancy did not increase offspring birthweight nor subsequent performance (Summers et al., 2015) but increased feedlot efficiency and altered carcass characteristics with a tendency for high fat concentrations in the meat of animal born to restricted, non-supplemented heifers (Summers et al., 2015).
In rabbits, a 50% maternal undernutrition from 7 to 19 days or from 20 to 27 days of gestation (31 days pregnancy) reduced pups' birthweight but post-natal growth, feeding behavior and body composition were not altered until 2,5 months of age (Lopez-Tello et al., 2017).
Thus, whatever the species, although maternal undernutrition may not alter birthweight, offspring lipid and glucose metabolism are usually disturbed, affecting body composition and muscular development.

Effect of maternal metabolism
Independently from nutrition, maternal metabolism can be affected by many factors.Insulinoresistance is usually linked to obesity but can also be associated to production.Indeed, high yielding dairy cattle are prone to insulinoresistance because of their high energy requirements for milk production inducing a negative energy balance and this lactational insulinoresistance can persist for subsequent pregnancies (Bossaert et al., 2008;De Koster and Opsomer, 2013;Zachut et al., 2013;Opsomer et al., 2017).Dairy cows insulinoresistant in late gestation produce lighter calves with reduced IGF1 plasma concentrations and increased insulinemia at birth (Kawashima et al., 2016).Effects on subsequent offspring production have not been studied but epidemiological data indicate a slightly reduced milk yield if offspring from dams inseminated at peak lactation (González-Recio et al., 2012).

Effect of maternal parity
The study of maternal age and parity on offspring development is difficult in production animals as age and parity are usually linked.Heifers are also non-lactating at breeding in contrast to cows.

Practical implications for embryo transfer
The data presented above show clear evidence that maternal size and nutrition may influence offspring size but also metabolism and production.Other production and health traits, such as immunity, feeding behavior but also fertility may also be affected (Chadio and Kotsampasi, 2014;Chavatte-Palmer et al. 2014).This pleads for a very careful choice of embryo recipients in terms of breed and size but also underlines the importance of the management of these animals before and during pregnancy.The molecular basis for these effects is epigenetic mechanisms (Gonzalez-Recio et al., 2015;Triantaphyllopoulos et al., 2016).Future research is needed to explore if epigenetic markers could be used as predictors of long term outcomes in offspring.

Table 1 .
Summary of studies performed on the effects of overnutrition in pregnant ewes on the post-natal development of the offspring.The level of excess nutrition is expressed as a percentage of the energy content ingested by the control group.

Table 2 .
Summary of studies performed on the effects of undernutrition in pregnant ewes on the post-natal development of the offspring.The level of undernutrition is expressed as a percentage of the energy content ingested by the control group.