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Placental development during early pregnancy in sheep: effects of embryo origin on vascularization.

ABSTRACT: Utero-placental growth and vascular development are critical for pregnancy establishment that may be altered by various factors including assisted reproductive technologies (ART), nutrition, or others, leading to compromised pregnancy. We hypothesized that placental vascularization and expression of angiogenic factors are altered early in pregnancies after transfer of embryos created using selected ART methods. Pregnancies were achieved through natural mating (NAT), or transfer of embryos from NAT (NAT-ET), or IVF or in vitro activation (IVA). Placental tissues were collected on day 22 of pregnancy. In maternal caruncles (CAR), vascular cell proliferation was less (P<0.05) for IVA than other groups. Compared with NAT, density of blood vessels was less (P<0.05) for IVF and IVA in fetal membranes (FM) and for NAT-ET, IVF, and IVA in CAR. In FM, mRNA expression was decreased (P<0.01-0.08) in NAT-ET, IVF, and IVA compared with NAT for vascular endothelial growth factor (VEGF) and its receptor FLT1, placental growth factor (PGF), neuropilin 1 (NP1) and NP2, angiopoietin 1 (ANGPT1) and ANGPT2, endothelial nitric oxide synthase 3 (NOS3), hypoxia-inducible factor 1A (HIF1A), fibroblast growth factor 2 (FGF2), and its receptor FGFR2. In CAR, mRNA expression was decreased (P<0.01-0.05) in NAT-ET, IVF, and IVA compared with NAT for VEGF, FLT1, PGF, ANGPT1, and TEK. Decreased mRNA expression for 12 of 14 angiogenic factors across FM and CAR in NAT-ET, IVF, and IVA pregnancies was associated with reduced placental vascular development, which would lead to poor placental function and compromised fetal and placental growth and development.

SUBMITTER: Grazul-Bilska AT

PROVIDER: S-EPMC3981880 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Placental development during early pregnancy in sheep: effects of embryo origin on vascularization.

Grazul-Bilska Anna T AT Johnson Mary Lynn ML Borowicz Pawel P PP Bilski Jerzy J JJ Cymbaluk Taylor T Norberg Spencer S Redmer Dale A DA Reynolds Lawrence P LP

Reproduction (Cambridge, England) 20140408 5

Utero-placental growth and vascular development are critical for pregnancy establishment that may be altered by various factors including assisted reproductive technologies (ART), nutrition, or others, leading to compromised pregnancy. We hypothesized that placental vascularization and expression of angiogenic factors are altered early in pregnancies after transfer of embryos created using selected ART methods. Pregnancies were achieved through natural mating (NAT), or transfer of embryos from N ...[more]

PMID: 24472816

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Project description:BackgroundAdministration of progesterone (P4) to ewes during the first 9 to 12 days of pregnancy accelerates blastocyst development by day 12 of pregnancy, likely due to P4-induced up-regulation of key genes in uterine epithelia responsible for secretion and transport of components of histotroph into the uterine lumen. This study determined if acceleration of blastocyst development induced by exogenous P4 during the pre-implantation period affects fetal-placental development on day 125 of pregnancy. Suffolk ewes (n = 35) were mated to fertile rams and assigned randomly to receive daily intramuscular injections of either corn oil vehicle (CO, n = 18) or 25 mg progesterone in CO (P4, n = 17) for the first 8 days of pregnancy. All ewes were hysterectomized on day 125 of pregnancy and: 1) fetal and placental weights and measurements were recorded; 2) endometrial and placental tissues were analyzed for the expression of candidate mRNAs involved in nutrient transport and arginine metabolism; and 3) maternal plasma, fetal plasma, allantoic fluid, and amniotic fluid were analyzed for amino acids, agmatine, polyamines, glucose, and fructose.ResultsTreatment of ewes with exogenous P4 did not alter fetal or placental growth, but increased amounts of aspartate and arginine in allantoic fluid and amniotic fluid, respectively. Ewes that received exogenous P4 had greater expression of mRNAs for SLC7A1, SLC7A2, SLC2A1, AGMAT, and ODC1 in endometria, as well as SLC1A4, SLC2A5, SLC2A8 and ODC1 in placentomes. In addition, AZIN2 protein was immunolocalized to uterine luminal and glandular epithelia in P4-treated ewes, whereas AZIN2 localized only to uterine luminal epithelia in CO-treated ewes.ConclusionsThis study revealed that exogenous P4 administered in early pregnancy influenced expression of selected genes for nutrient transporters and the expression of a protein involved in polyamine synthesis on day 125 of pregnancy, suggesting a 'programming' effect of P4 on gene expression that affected the composition of nutrients in fetal-placental fluids.

Project description:The mechanism underlying the potential risk associated with in vitro fertilization and embryo transfer (IVF?ET) has been previously investigated but remains to be fully elucidated. As the placenta is a critical organ that sustains and protects the fetus, this is an important area of research. The aim of the present study was to determine the difference in trophoblast cell function in the first trimester between naturally conceived pregnancies and pregnancies achieved via IVF?ET therapy. A total of 20 placental villi in first trimester samples were obtained through fetal bud aspiration from patients undergoing IVF?ET due to oviductal factors between January 2016 and August 2018. In addition, a further 20 placental villi were obtained from those who naturally conceived and had normal pregnancies but were undergoing artificial abortion; these patients were recruited as the controls. Reverse transcription?quantitative (RT?q)PCR and semi?quantitative immunohistochemical methods were used to detect the mRNA and protein expression of ??fetoprotein (AFP), vascular endothelial growth factor (VEGF), transferrin (TF), tubulin ?1 class VI (TUBB1), metallothionein 1G (MT1G), BCL2, glial cells missing transcription factor 1 (GCM1), epidermal growth factor (EGF) receptor (EGFR), PTEN and leukocyte associated immunoglobulin like receptor 2 (LAIR2) in villi from both groups. Differentially expressed genes were analyzed using Search Tool for the Retrieval of Interacting Genes, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted. The RT?qPCR data revealed that the mRNA expression levels of AFP, VEGF and TF were significantly higher in the IVF?ET group than in the control group (P<0.05), and those of TUBB1, MT1G, BCL2, GCM1, EGFR, PTEN and LAIR2 were significantly lower (P<0.05). These gene products were expressed in the placental villus tissues, either in the cytoplasm, or in the membrane of syncytiotrophoblast and cytotrophoblast cells. The immunohistochemistry results were in line with those observed using RT?qPCR. KEGG pathway analysis indicated that the trophoblast cell function of the IVF?ET group in the first trimester was different from naturally conceived pregnancies with regard to proliferation, invasion, apoptosis and vascular development. The IVF?ET process may trigger adaptive placental responses, and these compensatory mechanisms could be a risk for certain diseases later in life.

Project description:Many children adversely affected by maternal drinking during pregnancy cannot be identified early in life using current diagnostic criteria for fetal alcohol spectrum disorder (FASD). We conducted a preliminary investigation to determine whether ethanol-induced alterations in placental gene expression may have some utility as a diagnostic indicator of maternal drinking during pregnancy and as a prognostic indicator of risk for adverse neurobehavioral outcomes in affected offspring. Pregnant Long-Evans rats voluntarily consumed either a 0 or 5% ethanol solution 4 h each day throughout gestation. Ethanol consumption produced a mean maternal daily intermittent peak serum ethanol concentration of 84 mg/dL. Placentas were harvested on gestational day 20 for gene expression studies. Microarray analysis of more than 28,000 genes revealed that the expression of 304 known genes was altered twofold or greater in placenta from ethanol-consuming dams compared with controls. About 76% of these genes were repressed in ethanol-exposed placentas. Gene expression changes involved proteins associated with central nervous system development; organ morphogenesis; immunological responses; endocrine function; ion homeostasis; and skeletal, cardiovascular, and cartilage development. To date, quantitative real-time polymerase chain reaction analysis has confirmed significant alterations in gene expression for 22 genes, including genes encoding for three calcium binding proteins, two matrix metalloproteinases, the cannabinoid 1, galanin 2 and toll-like receptor 4, iodothyronine deiodinase 2, 11-β hydroxysteroid dehydrogenase 2, placental growth factor, transforming growth factor alpha, gremlin 1, and epithelial growth factor (EGF)-containing extracellular matrix protein. These results suggest that the expression of a sufficiently large number of placental mRNAs is altered after moderate drinking during pregnancy to warrant more detailed investigation of the placenta as a biomarker system for maternal drinking during pregnancy and as an early indicator of FASD. Furthermore, these results provide new insights into novel mechanisms on how ethanol may directly or indirectly mediate its teratogenic effects through alterations in placental function during pregnancy.

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Placental development during early pregnancy in sheep: effects of embryo origin on vascularization.

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Placental development during early pregnancy in sheep: effects of embryo origin on vascularization.

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