Growth and development of the ovine conceptus1

Bazer, Fuller W.; Spencer, Thomas E.; Thatcher, W.W.

doi:10.2527/jas.2011-4180

Cited by 59 publications

(40 citation statements)

References 58 publications

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“…In ewes, for example, the maximum concentration of glucose in allantoic fluid is 1.1 mM between days 35 and 140 of pregnancy, whereas the concentration of fructose is between 11.1 and 33 mM during the same period (32). Therefore, in accordance with the results shown in Fig.…”

Section: Discussionsupporting

confidence: 89%

“…A study to determine amino acid concentrations in ovine allantoic fluid and amniotic fluid, as well as in fetal and maternal plasma in pregnant ewes between days 30 and 140 of gestation, revealed that alanine, glutamine, glycine, and serine contributed 50% of total α-amino acids in fetal plasma (35). Interestingly, concentrations of alanine, citrulline, and glutamine in allantoic fluid increased 20-, 34-, and 18-fold, respectively, between days 30 and 60 of gestation and were 24.7, 9.7, and 23.5 mM, respectively, during this period of rapid placental growth and development (32,35). Remarkably, in sheep, alanine, citrulline, and glutamine accounted for ∼80% of total α-amino acids in allantoic fluid during early gestation, when both the concentration and total amount of fructose increase rapidly (35).…”

Section: Discussionmentioning

confidence: 92%

See 1 more Smart Citation

Functional roles of fructose

Kim

Song

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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During the periimplantation period of pregnancy, pig blastocysts undergo morphological changes and differentiation requiring secretion and transport of nutrients (histotroph) into the uterine lumen. Of these nutrients, glucose is converted to fructose, an isomer of glucose, by conceptus trophectoderm. Although glucose is an energy source for proliferation and growth of mammalian cells, the role of fructose in uterine histotroph is unclear although it is the most abundant hexose sugar in fetal blood and fluids of ungulate mammals (e.g., cows, sheep, and pigs). In this study, we used porcine trophectoderm cells to determine that fructose increased cell proliferation, as did glucose. Western blot analyses of porcine trophectoderm cell extracts revealed that fructose increased the abundance of phosphorylated-RPS6K, -EIF4EBP1, and -RPS6 over basal levels within 30 min, and those levels remained elevated to 120 min. Phosphorylation of both RPS6K and EIF4EBP1 proteins in response to fructose was inhibited by inhibitors of both PI3K and MTOR. Further, when we investigated the inhibition of glutamine-fructose-6-phosphate transaminase 1 (GFPT1) by azaserine (an inhibitor of GFPT1) and GFPT1 siRNA, we found that MTOR-RPS6K and MTOR-EIF4EBP1 signaling in response to fructose is mediated via GFPT1 activation and the hexosamine pathway. We further demonstrated that fructose stimulates the production of hyaluronic acid via GFPT1 and the hexosamine biosynthesis pathway. Collectively, these results demonstrate critical roles for fructose that are mediated via the hexosamine biosynthesis pathway to stimulate MTOR cell signaling, proliferation of porcine trophectoderm cells, and synthesis of hyaluronic acid, a significant glycosaminoglycan in the pregnant uterus.trophoblast | glycosaminoglycans D omestic livestock species are invaluable animal models used extensively in research relevant to human and veterinary reproductive medicine as well as basic biological and biomedical sciences (1, 2). In particular, the ewe is an established animal model for studies of intrauterine growth restriction during fetal life that is a predisposition for the adult onset of metabolic disease (3). Ewes have a protracted periimplantation period of pregnancy, a relatively short period of gestation, and are well suited for metabolic studies to assess temporal and cell-specific changes in gene expression in response to various hormones, growth factors, and nutrients that are relevant to human and veterinary medicine and basic aspects of reproductive biology. Although fructose clearly is the major hexose sugar in fetal blood and fetal fluids of ungulate species such as sheep and pigs, it is largely ignored with respect to function because it is not metabolized via the glycolytic pathway or the Krebs cycle as an energy source. Here we provide evidence that fructose affects multiple metabolic pathways critical to pregnancy and metabolism in multiple organ systems.Fructose is the most abundant hexose sugar in fetal fluids of ungulate mammals (4-6). Fructose ...

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 92%

Functional roles of fructose

Kim

Song

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…This data correlated with a more comprehensive data set published recently (32). Therefore we chose to use the published data to graph gestational age vs. fetal weight in order to extrapolate and approximate fetal weights on any given day between days 25 and 80.…”

Section: Methodssupporting

confidence: 78%

“…Fetal weight was estimated from a chart of fetal weight vs. gestation day generated using published data (32). …”

Section: Figurementioning

confidence: 99%

Influence of a dual-injection regimen, plerixafor and CXCR4 on in utero hematopoietic stem cell transplantation and engraftment with use of the sheep model

et al. 2014

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Background Inadequate engraftment of hematopoietic stem cells (HSCs) following in-utero HSC transplantation (IUHSCT) remains a major obstacle for the prenatal correction of numerous hereditary disorders. HSCs express CXCR4 receptors that allow homing and engraftment in response to SDF1 ligand present in the bone marrow (BM) stromal niche. Plerixafor, a mobilization drug, works through the interruption of the CXCR4-SDF1 axis. Methods We used the fetal sheep large animal model to test our hypotheses that: a) by administering plerixafor in-utero before performing IUHSCT to release fetal HSCs and thus vacating recipient HSC niches, b) by using human mesenchymal stromal/stem cells (MSCs) to immunomodulate and humanize the fetal BM niches, and c) by increasing the CXCR4+ fraction of CD34+ HSCs, we could improve engraftment. Human cord blood-derived CD34+ cells and human bone marrow-derived MSCs were used for these studies. Results When MSCs were transplanted one week prior to CD34+ cells with plerixafor treatment, we observed 2.80% donor hematopoietic engraftment. Combination of this regimen with additional CD34+ cells at the time of MSC infusion increased engraftment levels to 8.77%. Next, increasing the fraction of CXCR4+ cells in the CD34+ population albeit transplanting at a late gestation age was not beneficial. Our results show engraftment of both lymphoid and myeloid lineages. Discussion Prior MSC and HSC cotransplantation followed by manipulation of the CXCR4-SDF1 axis in IUHSCT provides an innovative conceptual approach for conferring competitive advantage to donor HSCs. Our novel approach could provide a clinically relevant approach for enhancing engraftment early in the fetus.

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“…Because of the small size of the organs (around 2g; Bazer et al, 2012), the livers from six male and six female early-stage fetuses were pooled as follows: three pools of two males and three pools of two females. Livers from the six near-term fetuses (three males, three females) and from the three nonpregnant ewes were processed individually.…”

Section: Characterization Of Bpa Conjugation/deconjugation Activitiesmentioning

confidence: 99%

Conjugation and Deconjugation Reactions within the Fetoplacental Compartment in a Sheep Model: A Key Factor Determining Bisphenol A Fetal Exposure

et al. 2015

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The widespread human exposure to bisphenol A (BPA), an endocrine disruptor targeting developmental processes, underlines the need to better understand the mechanisms of fetal exposure. Animal studies have shown that at a late stage of pregnancy BPA is efficiently conjugated by the fetoplacental unit, mainly into BPAglucuronide (BPA-G), which remains trapped within the fetoplacental unit. Fetal exposure to BPA-G might in turn contribute to in situ exposure to bioactive BPA, following its deconjugation into parent BPA at the level of fetal sensitive tissues. The objectives of our study were 1) to characterize the BPA glucurono-and sulfoconjugation capabilities of the ovine fetal liver at different developmental stages, 2) to compare hepatic conjugation activities in human and sheep, and 3) to evaluate the extent of BPA conjugation and deconjugation processes in placenta and fetal gonads. At an early stage of pregnancy, and despite functional sulfoconjugation activity, ovine fetuses expressed low hepatic BPA conjugation capabilities, suggesting that this stage of development represents a critical window in terms of BPA exposure. Conversely, the late ovine fetus expressed an efficient detoxification system that metabolized BPA into BPA-G. Hepatic glucuronidation activities were quantitatively similar in adult sheep and humans. In placenta, BPA conjugation and BPA-G deconjugation activities were relatively balanced, whereas BPA-G hydrolysis was systematically higher than BPA conjugation in gonads. The possible reactivation of BPA-G into BPA could contribute to an increased exposure of fetal sensitive tissues to bioactive BPA in situ.

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Growth and development of the ovine conceptus1

Cited by 59 publications

References 58 publications

Functional roles of fructose

Functional roles of fructose

Influence of a dual-injection regimen, plerixafor and CXCR4 on in utero hematopoietic stem cell transplantation and engraftment with use of the sheep model

Conjugation and Deconjugation Reactions within the Fetoplacental Compartment in a Sheep Model: A Key Factor Determining Bisphenol A Fetal Exposure

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