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      Competition for Materno-Fetal Resource Partitioning in a Rabbit Model of Undernourished Pregnancy

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          Abstract

          The major goal of animal production is to obtain abundant and healthy meat for consumers. Maternal food restriction (MFR) is often applied in farms to reduce production costs. However, the suitability of MFR in livestock animals is questionable, as this management may compromise maternal fitness due to a severe negative energetic balance and can induce Intrauterine Growth Restriction (IUGR) and prenatal programming in the offspring. Here, we sought to determine, using pregnant rabbits, the consequences of MFR on maternal endocrine and metabolic status and conceptus development. Pregnant dams were distributed into three groups: CONTROL ( ad libitum feeding throughout the entire pregnancy; mean pregnancy length being around 31 days), UNDERFED (50% MFR during the entire pregnancy) and EARLY-UNDERFED (50% MFR only during the preimplantation period, Days 0–7). Maternal leptin concentrations and glycemic and lipid profiles were determined throughout pregnancy, whilst conceptus development was assessed ex-vivo at Day 28. Placental parameters were determined by macroscopic and histological evaluations and apoptotic assessments (TUNEL and Caspase-3). The main results of the study showed that, despite MFR altered maternal plasma lipid concentration (P<0.05), there were no effects on maternal bodyweight, plasma leptin concentration or glycemic profile. Fetal crown-rump lengths were reduced in both undernourished groups (P<0.001), but a significant reduction in fetal weight was only observed in the UNDERFED group (P<0.001). Growth in both undernourished groups was asymmetrical, with reduced liver weight (P<0.001) and significantly increased brain: fetal weight-ratio (P<0.001) and brain: liver weight-ratio (P<0.001) when compared to the CONTROL group. A significant reduction in placental weight was only observed in the UNDERFED group (P<0.001), despite both undernourished groups showing higher apoptotic rates at decidua and labyrinth zone (P<0.05) than the CONTROL group. Thus, these groups evidenced signs of placental degeneration, necrosis and stromal collapse. In summary, MFR may encourage the mother to make strategic decisions to safeguard her metabolic status and fitness at the expense of growth reduction in the litter, resulting in enhanced apoptotic and pathological processes at placental level and IUGR.

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          Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension.

          Epidemiological studies have indicated that susceptibility of human adults to hypertension and cardiovascular disease may result from intrauterine growth restriction and low birth weight induced by maternal undernutrition. Although the 'foetal origins of adult disease' hypothesis has significant relevance to preventative healthcare, the origin and biological mechanisms of foetal programming are largely unknown. Here, we investigate the origin, embryonic phenotype and potential maternal mechanisms of programming within an established rat model. Maternal low protein diet (LPD) fed during only the preimplantation period of development (0-4.25 days after mating), before return to control diet for the remainder of gestation, induced programming of altered birthweight, postnatal growth rate, hypertension and organ/body-weight ratios in either male or female offspring at up to 12 weeks of age. Preimplantation embryos collected from dams after 0-4.25 days of maternal LPD displayed significantly reduced cell numbers, first within the inner cell mass (ICM; early blastocyst), and later within both ICM and trophectoderm lineages (mid/late blastocyst), apparently induced by a slower rate of cellular proliferation rather than by increased apoptosis. The LPD regimen significantly reduced insulin and essential amino acid levels, and increased glucose levels within maternal serum by day 4 of development. Our data indicate that long-term programming of postnatal growth and physiology can be induced irreversibly during the preimplantation period of development by maternal protein undernutrition. Further, we propose that the mildly hyperglycaemic and amino acid-depleted maternal environment generated by undernutrition may act as an early mechanism of programming and initiate conditions of 'metabolic stress', restricting early embryonic proliferation and the generation of appropriately sized stem-cell lineages.
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            Maternal undernutrition influences placental-fetal development.

            Maternal nutrition during pregnancy has a pivotal role in the regulation of placental-fetal development and thereby affects the lifelong health and productivity of offspring. Suboptimal maternal nutrition yields low birth weight, with substantial effect on the short-term morbidity of the newborn. The placenta is the organ through which gases, nutrients, and wastes are exchanged between the maternal-fetal circulations. The size, morphology, and nutrient transfer capacity of the placenta determine the prenatal growth trajectory of the fetus to influence birth weight. Transplacental exchange depends on uterine, placental, and umbilical blood flow. Most important, maternal nutrition influences factors associated not only with placental homeostasis but also with optimal fetal development. This review associates fetal growth with maternal nutrition during pregnancy, placental growth and vascular development, and placental nutrient transport.
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              Prenatal undernutrition and cognitive function in late adulthood.

              At the end of World War II, a severe 5-mo famine struck the cities in the western part of The Netherlands. At its peak, the rations dropped to as low as 400 calories per day. In 1972, cognitive performance in 19-y-old male conscripts was reported not to have been affected by exposure to the famine before birth. In the present study, we show that cognitive function in later life does seem affected by prenatal undernutrition. We found that at age 56 to 59, men and women exposed to famine during the early stage of gestation performed worse on a selective attention task, a cognitive ability that usually declines with increasing age. We hypothesize that this decline may be an early manifestation of an accelerated cognitive aging process.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                3 January 2017
                2017
                : 12
                : 1
                : e0169194
                Affiliations
                [1 ]Department of Animal Production, Veterinary Faculty, Complutense University of Madrid, Ciudad Universitaria, Madrid, Spain
                [2 ]Department of Animal Medicine and Surgery, Veterinary Faculty, Complutense University of Madrid, Ciudad Universitaria, Madrid, Spain
                [3 ]Department of Physiology (Animal Physiology), Veterinary Faculty, Complutense University of Madrid, Ciudad Universitaria, Madrid, Spain
                [4 ]Department of Agrarian Production, E.T.S.I.A.A.B. Polytechnic University of Madrid, Ciudad Universitaria, Madrid, Spain
                [5 ]Comparative Physiology Group, SGIT-INIA, Avda. Puerta de Hierro, Madrid, Spain
                University of Southampton, UNITED KINGDOM
                Author notes

                Competing Interests: There is no conflict of interest that would prejudice the information offered in the paper, excepting that AG-B is a PLOS ONE Editorial Board member. However, this does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

                • Conceptualization: JL-T MA-A PGR.

                • Formal analysis: JL-T MA-A RB-P AG-B PGR.

                • Methodology: JL-T MA-A MAJ-M RMG-G MR PLLG RB-P AG-B PGR.

                • Writing – original draft: JL-T MA-A MAJ-M AG-B PGR.

                • Writing – review & editing: JL-T MA-A MAJ-M RMG-G MR PLLG RB-P AG-B PGR.

                Author information
                http://orcid.org/0000-0002-0917-4475
                Article
                PONE-D-16-24553
                10.1371/journal.pone.0169194
                5207739
                28046002
                0072edbf-639e-491c-a2e4-99030fdce2a0
                © 2017 Lopez-Tello et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 June 2016
                : 13 December 2016
                Page count
                Figures: 5, Tables: 1, Pages: 18
                Funding
                Funded by: Spanish Ministry of Science and Technology
                Award ID: AGL2011-23822
                Award Recipient :
                Funded by: Comunidad de Madrid
                Award ID: S2013/ABI-2913
                Award Recipient :
                Funded by: Spanish Ministry of Science and Technology
                Award ID: AGL2015-65572-C2-1-R
                This research was supported by funding from the Spanish Ministry of Science and Technology (AGL2011-23822; AGL2015-65572-C2-1-R) and Comunidad de Madrid (S2013/ABI-2913). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Research and Analysis Methods
                Experimental Organism Systems
                Animal Models
                Rabbits
                Biology and Life Sciences
                Organisms
                Animals
                Vertebrates
                Amniotes
                Mammals
                Rabbits
                Biology and Life Sciences
                Developmental Biology
                Embryology
                Placenta
                Biology and Life Sciences
                Anatomy
                Reproductive System
                Placenta
                Medicine and Health Sciences
                Anatomy
                Reproductive System
                Placenta
                Medicine and Health Sciences
                Women's Health
                Maternal Health
                Pregnancy
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Pregnancy
                Biology and Life Sciences
                Anatomy
                Reproductive System
                Uterus
                Decidua
                Medicine and Health Sciences
                Anatomy
                Reproductive System
                Uterus
                Decidua
                Biology and Life Sciences
                Cell Biology
                Cell Processes
                Cell Death
                Apoptosis
                Biology and Life Sciences
                Developmental Biology
                Embryology
                Fetuses
                Biology and Life Sciences
                Biochemistry
                Hormones
                Peptide Hormones
                Leptin
                Biology and Life Sciences
                Agriculture
                Livestock
                Custom metadata
                All relevant data are within the paper.

                Uncategorized
                Uncategorized

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