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Impact of chorionic somatomammotropin in vivo RNA interference phenotype on uteroplacental expression of the IGF axis

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dc.contributor.authorHord, Taylor, author
dc.contributor.authorAnthony, Russel V., advisor
dc.contributor.authorWinger, Quinton A., advisor
dc.contributor.authorBruemmer, Jason, committee member
dc.contributor.authorKading, Rebekah, committee member
dc.date.accessioned2023-08-28T10:27:49Z
dc.date.available2023-08-28T10:27:49Z
dc.date.issued2023
dc.description.abstractWhile fetal growth is dependent on many factors, optimal placental function is a prerequisite for a normal pregnancy outcome. The majority of fetal growth restricted (FGR) pregnancies result from placental insufficiency (PI). The insulin-like growth factors (IGF1 and IGF2) not only stimulate fetal growth, but also placental development and function. Previously, we demonstrated that in vivo RNA interference (RNAi) of the placental hormone, chorionic somatomammotropin (CSH), resulted in two phenotypes. One phenotype exhibits significant placental and fetal growth restriction (PI-FGR), impaired placental nutrient transport, and significant reductions in umbilical insulin and IGF1. The other phenotype does not exhibit statistically significant changes in placental or fetal growth (non-FGR). It was our objective to further characterize these two phenotypes by determining the impact of CSH RNAi on placental (maternal caruncle and fetal cotyledon) expression of the IGF axis. The trophectoderm of hatched blastocysts (9 days of gestation, dGA) were infected with a lentivirus expressing either a non-targeting sequence (NTS RNAi) control or CSH-specific shRNA (CSH RNAi) prior to embryo transfer into synchronized recipient ewes. At ≈125 dGA, pregnancies were fitted with vascular catheters to undergo steady-state metabolic studies. Nutrient uptakes were determined and tissues were harvested at necropsy. In both CSH RNAi non-FGR and PI-FGR pregnancies, uterine blood flow was significantly reduced (P≤0.05), while umbilical blood flow (P≤0.01), both uterine and umbilical glucose and oxygen uptakes (P≤0.05), and umbilical concentrations of insulin and IGF1 (P≤0.05) were reduced in CSH RNAi PI-FGR pregnancies. Fetal cotyledon IGF1 mRNA concentration was reduced (P≤0.05) in CSH RNAi PI-FGR pregnancies, whereas neither IGF1 nor IGF2 mRNA concentrations were impacted in the maternal caruncles, and either placental tissue in the non-FGR pregnancies. Fetal cotyledon IGF1R and IGF2R mRNA concentrations were not impacted for either phenotype, yet IGF2R was increased (P≤0.01) in the maternal caruncles of CSH RNAi PI-FGR pregnancies. For the IGF binding proteins (IGFBP1, IGFBP2, IGFBP3), only IGFBP2 mRNA concentrations were impacted, with elevated IGFBP2 mRNA in both the fetal cotyledon (P≤0.01) and maternal caruncle (P=0.08) of CSH RNAi non-FGR pregnancies. These data support the importance of IGF1 in placental growth and function, but may also implicate IGFBP2 in salvaging placental growth in non-FGR pregnancies.
dc.format.mediumborn digital
dc.format.mediummasters theses
dc.identifierHord_colostate_0053N_17864.pdf
dc.identifier.urihttps://hdl.handle.net/10217/236804
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2020-
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectfetal growth restriction
dc.subjectIGF2
dc.subjectRNA interference
dc.subjectIGF1
dc.subjectCSH
dc.subjectplacenta
dc.titleImpact of chorionic somatomammotropin in vivo RNA interference phenotype on uteroplacental expression of the IGF axis
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorColorado State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (M.S.)

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