Conceptus Competition for Nutrients in the Porcine Uterus: Different Strategies Exhibited by the Meishan and Yorkshire Pig Breeds

Previous research from our laboratory demonstrated that Meishan conceptuses develop more slowly and synchronously to day 30 of gestation than conceptuses of U.S. pig breeds. Furthermore, the reduced size of the Meishan conceptus on day 30 allows more Meishan than Yorkshire conceptuses to occupy the same amount of limited uterine space. As a result, Meishan litter size is significantly larger than that of U.S. pig breeds (13−14 vs. 9-10 piglets/litter). An additional consistent, but unexpected, finding in the Meishan pig was the observation that there was significantly greater amounts of unoccupied uterine space in the Meishan than the Yorkshire female at term. We previously demonstrated that an additional strategy of the Meishan female to increase fecundity was to super-vascularize its placental membranes so that oxygen and nutrient transfer from the sow could be accomplished over a reduced surface area, negating the necessity of further placental growth. These data suggested that when a Meishan conceptus dies, the placenta of its neighbors need not grow into this newly vacated space, whereas the Yorkshire conceptus might increase the size of its less vascular placenta to use the opportunity. Therefore, it was our objective to confirm that Yorkshire conceptuses, but not Meishan conceptuses increase their placental size when adjacent conceptuses are experimentally destroyed on day 40 of gestation. To accomplish this objective, pregnant Meishan and Yorkshire females were laporatomized on day 40. One uterine horn was randomly chosen to be receive alternative fetal crushing (i.e., every other fetus in the horn was crushed by mechanical pressure), whereas the other uterine horn served as the control horn. At slaughter on day 111 of gestation (term = 114 days), we found no differences in fetal weight between the control and treated horns regardless of breed. Similarly, there was no difference in placental weight or surface area or implantation site length (the length of placental attachment in the uterine horn) between the control and treated horns in the Meishan. In contrast, however, there was a marked increase in placental weight and surface area, as well as implantation site length for conceptuses in the treated horn of the Yorkshire gilts versus the control horn. Furthermore, the unoccupied spaces between Meishan conceptuses in the treated horn were 2-fold greater than for conceptuses in the control horn, whereas there were no differences in the length of unoccupied spaces between conceptuses in the Yorkshire’s control or treated horns. These data suggest that in the Meishan treated horn, conceptuses do not use this extra space as effectively as conceptuses in the Yorkshire treated horn. The inability of Meishan placenta to grow into adjacent unoccupied spaces may not be detrimental to conceptus survival due to its greater ability to increase vascular density in response to increasing fetal demands. If U.S. pig breeds have the potential to increase placental vascularity, rather than increase in placental size to nourish the growing fetuses, the potential exists for increasing litter size due to a decrease in uterine competition throughout gestation

Use of Asynchronous Embryo Transfer to Investigate the Role of Uterine-embryo Timing on Placental Size

The ability of the uterus to accommodate a finite amount of placental tissue appears to be a major limitation to litter size. Meishan preimplantation conceptuses contain fewer cells, produce less estradiol-17β, elongate to a shorter length, and exhibit a reduced placental size throughout gestation than Yorkshire conceptuses. Uterine luminal embryonic estradiol-17β and growth factor content are positively associated at elongation. Based on these data, we have argued that growth factor quantity regulates the length an embryo attains at elongation, and ultimately limits placental size. Recently, we injected Meishan gilts every 6 hours with estradiol-17β on day 12 and 13 of gestation, resulting in a 40% increase in placental size at term compared with vehicle-injected Meishan gilts. This study was conducted to determine if transfer of embryos into the oviducts of asynchronous females (more or less advanced uterine environments) would alter fetal and/or placental size at term. Embryos (1 to 4 cells) were flushed from the oviducts of each donor gilt on day 2.5 of gestation and transferred in equal numbers to the oviducts of a recipient gilt on day 1.5, 2.5, or 3.5 of their estrous cycle. Gilts were slaughtered on day 112 of gestation and fetal and placental weight, placental surface area, and implantation site lengths were determined. Although litter sizes were similar (8.4 ± 1.1), conceptuses transferred to day 3.5 recipients had heavier fetuses (1.57 ± .09 vs. 1.23 ± .04 kg, P\u3c.001), larger placental surface area (1812 ± 106 vs. 1458 ± 43 cm 2 , P\u3c.01) and occupied longer implantation site length (34 ± 3 vs. 25 ± 1 cm, P\u3c.001) than those transferred to recipients on day 1.5 or 2.5. These data demonstrate that oviductal transfer of embryos to a reproductive tract as little as 24 hours more advanced can result in dramatic alterations in placental growth and function during gestation

Role of Vascular Endothelial Growth Factor in Placental Vascularization

The ratio of a fetus’s weight to that of its placenta has been used in our laboratory as an estimate of placental efficiency, which defines the number of grams of placenta required to support a gram of fetus. Because the pig placenta is noninvasive, nutrients from the mother must diffuse from uterine blood vessels to placental blood vessels at the placental-endometrial interface. A pig placenta can respond to increasing fetal nutrient demands by either increasing in size, and thus surface area in contact with the endometrium, or by increasing the number of blood vessels per unit area at the fetal-maternal interface. Previous studies from our laboratory have shown Meishan and Yorkshire conceptuses gestated in a Meishan uterus had markedly smaller placentae than Meishan or Yorkshire conceptuses gestated in a Yorkshire uterus whereas fetal weights across the two uterine environments were much more similar. These data suggested that conceptuses in a Meishan uterine environment have a greater vascular density at the placentalendometrial interface. Greater densities of blood vessels can be achieved by either vasodilation (increasing the diameter of existing blood vessels) or angiogenesis (growth of new vessels from preexisting ones). Hypoxia, or inadequate oxygen transport, has been shown to increase angiogenic factors, such as vascular endothelial growth factor (VEGF), which stimulate blood vessel development. It is possible that VEGF may be important in stimulating increased blood vessel density in the pig placenta, as it has been to shown to do in the ovine placenta. Our objective was to determine if VEGF mRNA expression was associated with placental and/or endometrial vascular density, placental efficiency, and litter size during late gestation. We observed a positive association of both placental vascular density (r=0.37, p\u3c0.05) and VEGF mRNA levels (r=0.35; P\u3c.05) with placental efficiency . There was also a positive correlation between VEGF mRNA levels and the number of conceptuses in a litter (r=0.42; P\u3c.05) on day 70, 90, and 110 of gestation. Although Yorkshire uteri exhibited greater endometrial vascular density than Meishan uteri on day 70 of gestation, placentae of conceptuses gestated in a Meishan uterus had greater amounts of VEGF mRNA than placentae of conceptuses gestated in a Yorkshire uterus. The greater amounts of placental VEGF mRNA of conceptuses gestated in a Meishan uterus on day 70 may have resulted in the increased placental vascular density observed on day 90. We conclude that the increased litter size of the Meishan female may stem from her having smaller, more vascular placentae than placentae of conceptuses gestated in the uterus of a Yorkshire female, to allow for efficient nutrient delivery to the fetus. The increased placental vascular density of a conceptus gestated in the uterus of a Meishan female may result from increased placental VEGF mRNA production induced from an endometrial induced hypoxia on day 70 of gestation

Ovarian responses to undernutrition in pregnant ewes, USA

In most mammals oogonia proliferate by mitosis and begin meiotic development during fetal life. Previous studies indicated that there is a delay in the progression to the first stage of meiotic arrest in germ cells of female fetuses of undernourished ewes. We report that underfeeding (50% NRC requirement beginning on Day 28 of pregnancy) provokes an increase in oxidative base lesions within DNA of mid-gestational (Day 78) fetal oogonia; this condition was associated with up-regulation of the tumor suppressor/cell-cycle arrest modulator p53, antiapoptotic factor Bcl-2, and base-excision repair polymerase β. Fetal ovarian weights and germ cell concentrations were not altered by nutrient deprivation. Ovaries of ewes on control diets (100% NRC) contained more tertiary follicles than their restricted counterparts; however, peripheral venous estradiol-17β was not different between groups. There was no effect of treatment on p53 accumulation in maternal oocytes. Luteal structure-function was not perturbed by undernutrition. No fetal losses were attributed to the dietary restriction. It is proposed that DNA of interphase fetal oogonia is vulnerable to oxidative insults perpetrated by a nutritional stress to the dam, and that multiple/integrated adaptive molecular response mechanisms of cell-cycle inhibition (providing the time required for base repairs) and survival hence sustain the genomic integrity and population stability of the germline

Controls of Litter Size—Do Conclusions Drawn from Institutional Research Herds Always Have Relevance to Commercial Swine Production?

Increasing litter size in pigs has been an ongoing concern of many producers because it has the greatest impact on profitability of the swine enterprise. To study the biology of conceptus growth and survival, many models have been used by researchers. It was determined that a major component in limiting litter size results from the impacts of limitations in uterine space (i.e. uterine capacity). Placental efficiency, which is the ratio of a fetus’s weight compared with that of its placenta, has been shown to impact litter size, and is heritable. Selection for breeding animals having a high placental efficiency at term, has been shown to increase litter size. Furthermore, although piglet weight was only slightly decreased in offspring of boars and gilts selected for increased placental efficiency, placental size was profoundly reduced. This reduction in placental size was coupled with an increase in vascularity, thus nutrient and oxygen uptake by the conceptus could be accomplished over a decreased surface area of attachment to the uterine wall. Reproductive data obtained to date have been gathered largely from university swine herds that may have little relevance to commercially used US pig breeds. In contrast to the constant evaluations of physiological changes associated with increased litter size at universities, swine seed stock producers have selected for many generations simply on increased litter size and have not bothered to evaluate the resulting physiological changes associated with increased fecundity. Therefore, it was the objective of this study to investigate the reproductive characteristics of a commercially relevant swine herd in Iowa (PIC Camborough Line) at selected gestational ages. Multiparous sows (ranging from 1 to 14 parities) were slaughtered on days 25, 36, and 44 of gestation, time periods corresponding to intervals which are before, during, and after the time when uterine capacity becomes limiting. At the laboratory, the uterine horns were measured and ovulation rate was determined. Conceptuses were removed and fetal and placental weights were determined. Uterine horn length and ovulation rate did not differ between the three gestational groups. Conceptus number decreased from 15.8 ± 0.6 on day 25 to 12.9 ± 0.5 and 12.1 ± 0.4 on day 36 and day 44 (litter size in this population averages ~11.5 liveborn piglets/litter). Conceptus survival to day 25 was 60.2 ± 0.1%, which then decreased to 50.1 ± 0.1% on day 36 and 46.3 ± 0.1% on day 44. There was a positive correlation between conceptus number and ovulation rate on day 25 but by day 36 this association was lost. Conceptus number was not associated with uterine length on day 25, but by day 36 there was a positive association that remained through day 44. On all three gestation days there was a negative association between conceptus number and placental weight, but no association between conceptus number and fetal weight was observed, indicating that larger litters are comprised of conceptuses having small placentae, but the same sized fetuses. These data indicate that, compared with commonly reported values for university herds (16-18 ovulations), ovulation rate in these mixed parity production animals is extremely high, whereas conceptus survival as estimated from the number of conceptuses divided by the number of ovulations was very low. Additionally, although conceptus number was related to the ovulation rate on day 25, by day 36 the limitations of uterine size began to reduce conceptus number irrespective of ovulation rate. These data suggest that ovulation rate is not a limiting factor in litter size in this line of commercially relevant pigs. In contrast, the higher than expected ovulation rate observed in these pigs resulted in significant embryo losses and early uterine crowding. The consequences of this early conceptus crowding may have detrimental impacts on prenatal and postnatal growth rate and survival

Impacts of Maternal Nutrition on Vascularity of Nutrient Transferring Tissues during Gestation and Lactation

As the demand for food increases with exponential growth in the world population, it is imperative that we understand how to make livestock production as efficient as possible in the face of decreasing available natural resources. Moreover, it is important that livestock are able to meet their metabolic demands and supply adequate nutrition to developing offspring both during pregnancy and lactation. Specific nutrient supplementation programs that are designed to offset deficiencies, enhance efficiency, and improve nutrient supply during pregnancy can alter tissue vascular responses, fetal growth, and postnatal offspring outcomes. This review outlines how vascularity in nutrient transferring tissues, namely the maternal gastrointestinal tract, the utero-placental tissue, and the mammary gland, respond to differing nutritional planes and other specific nutrient supplementation regimes

Thyroid Hormones and Cortisol Concentrations in Offspring are Influenced by Maternal Supranutritional Selenium and Nutritional Plane in Sheep

To determine the effects of maternal supranutritional selenium (Se) supplementation and maternal nutritional plane on offspring growth potential, ewes were randomly assigned to 1 of 6 treatments in a 2 × 3 factorial arrangement [dietary Se (adequate Se; 9.5 μg/kg body weight vs. high Se; 81.8 μg/kg body weight initiated at breeding) and plane of nutrition [60%, 100%, or 140% of requirements; initiated on day 50 of gestation]]. Lambs were immediately removed from dams at birth and reared. Cortisol concentrations at birth were similar, but by 24 h, a relationship ( P = 0.02) between maternal Se supplementation and nutritional plane on cortisol concentrations was observed in lambs. A sex of offspring × day of age interaction ( P = 0.01) and a maternal Se supplementation × nutritional plane × day of age interaction ( P = 0.04) was observed for thyroxine concentrations. Differences in growth may be influenced by thyroid hormone production early in neonatal life