Ontogeny of metabolic effects on embryonic development in lactating and weaned primiparous sows.

Using an established experimental paradigm, feed restriction during the last week of lactation in primiparous sows reduces embryonic growth and development and produces female-specific embryonic mortality by Day 30 of gestation. Because this gender-specific loss of embryos at Day 30 was associated with changes in the variation of markers of epigenetic imprinting, the present study sought to establish the ontogeny of such epigenetic affects. Leucocyte DNA of restrict-fed sows exhibited decreased global methylation during the last week of lactation and during the return to oestrus (P < 0.05), but no associated changes in plasma folate and vitamin B(12). Furthermore, no changes in methylation of blastocyst DNA, embryonic sex ratios or development were evident at Day 6 of gestation that would characterise the underlying defects that reduced female embryo survival by Day 30. However, regardless of treatment, embryo recovery rates and synchrony in embryonic development were associated with the stage of development of the recovered embryos (r = 0.68; P < 0.001). The subset of sows classified as bearing litters with superior embryonic development had lower net energy balance over lactation (P < 0.01) and higher ovulation rates (P < 0.005) compared with sows classified as having poorer embryonic development. Collectively, these data suggest that a subset of litters within restrict-fed sows will be most sensitive to the latent epigenetic mechanisms that ultimately trigger gender-specific loss of embryos by Day 30 of gestation, but that these selective mechanisms are not evident by Day 6 of gestation.

Macroenvironment effects on oocytes and embryos in swine.

As in other domestic mammals, the interaction between genotype and environment in swine has profound effects on the ultimate phenotype of the individual born. Interactions within the litter in utero add an additional level of complexity in a litter-bearing species like the pig. Nutritional manipulations during the preovulatory period affect the maturity of the follicle and enclosed oocyte, and the metabolic and endocrine mechanisms potentially mediating these effects have been described. Extensive research on lactational catabolism in the first parity sow has established an association between the development of immature follicles and oocytes, and the reduced fertility of these sows when bred at the first postweaning estrus. This negative impact of lactational catabolism appears to be exaggerated in contemporary dam-lines by a minimal delay between weaning and first estrus, further limiting the maturity of the follicle and oocyte at the time of ovulation. Metabolic programming may induce gender-specific loss of embryos by Day 30 and affects embryonic development directly, without significant effects on placental size. In contrast, inadvertent crowding of embryos in utero, particularly evident in a sub-population of mature sows with high ovulation rates and moderate to high embryonic survival to Day 30, significantly limits placental development of crowded litters. However, even at Day 30, moderate crowding in utero also appears to affect myogenesis in the embryo in a gender-specific manner. In the absence of compensatory placental growth after Day 30, classic measures of IUGR are evident in surviving fetuses at Day 90 and at term.

Altered epigenetic variance in surviving litters from nutritionally restricted lactating primiparous sows.

Feed restriction of primiparous sows during the last week of lactation has been shown to decrease embryonic growth and female embryo survival to Day 30 of gestation. This study sought to determine whether global DNA methylation and epigenetic gene expression of the candidate genes Igf2, Igf2r, and Xist were associated with these treatment effects. Given that these epigenetic traits are expected to be important for embryo viability, changes in variance for these traits at Day 30 were predicted to be reflected in the loss of abnormal embryos at this time. Consistent with this prediction, variance in DNA methylation was reduced (P < 0.001) in Restrict male embryo, and there was a tendency for reduced variance (P < 0.06) in Restrict female embryos. Variation in DNA methylation tended to be correlated (R = 0.42, P < 0.1) with the difference in variance of embryo weights between treatments (P < 0.01), suggesting a relationship between epigenetic changes and embryonic development. Variance in Igf2r expression tended to decrease (P < 0.07) in Restrict female embryos while variance in Xist expression tended to decrease in Restrict male embryos (P < 0.08), suggesting that maternally inherited epigenetic defects may cause female embryonic loss and reduced growth before Day 30 of gestation.

The biological basis for prenatal programming of postnatal performance in pigs.

The main purpose of this review is to discuss associations between within-litter variation in birth weight, and preweaning survival and postnatal growth in the pig, as the basis for suggesting that the developmental competence of pigs born, as well as the size of the litter, need critical consideration. Extremes of intrauterine growth retardation (IUGR) occur within a discrete subset of fetuses, substantially smaller than their littermates and commonly described as runt piglets. The lower preweaning growth of runt pigs cannot be entirely explained based on their lower birth weight, nor do they show full postnatal compensatory growth. Interestingly, this more complex reprogramming of development in runt pigs can already be identified by d 27 to 35 of gestation. Recently, we reported more universal IUGR effects in commercial dam-line sows, as an indirect response to selection for increased litter size. High ovulation rates (>30 ovulations) in a proportion of greater parity sows are associated with increased numbers of conceptuses surviving to d 30 of gestation, resulting in detrimental effects on placental development of uterine crowding in the early postimplantation period. In turn, this limits nutrient availability to the embryo during a critical period of myogenesis. Consequently, although a reduction in the number of conceptuses occurs by d 50, placental development in the surviving fetuses remains compromised, resulting in IUGR and reduced numbers of muscle fibers at d 90 and at birth, in all surviving littermates. These effects of uterine crowding on fetal and postnatal development are analogous to the detrimental effects of nutritional restriction in gestating sows on fetal myogenesis, birth weight, and postnatal growth. The incompatibility between increased numbers of conceptuses surviving to the postimplantation period, in the absence of increased uterine capacity, offers a biological explanation for increased variability in birth weight and postnatal growth performance reported in greater parity sows. We conclude that a strategy of introducing hyperprolific females into the breeding nucleus, as a means of increasing the numbers of pigs born, needs to be critically evaluated in the context of the overall efficiency of pork production.

Nutritional restriction in lactating primiparous sows selectively affects female embryo survival and overall litter development.

This study explored the possibility of sex-specific effects on embryonic survival in primiparous sows subjected to restricted feed intake during the last week of lactation and bred after weaning (Restrict; n = 16), compared with control sows fed close to ad libitum feed intakes (Control; n = 17). Restrict sows were in a substantial negative net energy balance at weaning, and lost 13% of estimated protein and 17% of fat mass during lactation, yet the weaning-to-oestrous interval and ovulation rate were not different between treatments. However, embryonic survival at Day 30 of gestation was lower (P < 0.05) in Restrict than Control sows, and selectively reduced the proportion of female embryos surviving (P < 0.01). A decrease in weight and crown-rump length of surviving female (P < 0.05) and male (P < 0.05) embryos was seen in Restrict litters. The mechanisms mediating this sex-specific effect on embryonic loss in feed-restricted sows are unclear. The data presented here indicate that feed-restriction during the last week of lactation in primiparous sows causes a selective decrease in survival of female embryos and limits the growth of all surviving embryos.