Impact of Chorionic Somatomammotropin In Vivo RNA Interference Phenotype on Uteroplacental Expression of the IGF Axis
While 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) stimulate fetal growth and...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Life |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-1729/13/6/1261 |
| _version_ | 1827736749139296256 |
|---|---|
| author | Taylor K. Hord Amelia R. Tanner Victoria C. Kennedy Cameron S. Lynch Quinton A. Winger Paul J. Rozance Russell V. Anthony |
| author_facet | Taylor K. Hord Amelia R. Tanner Victoria C. Kennedy Cameron S. Lynch Quinton A. Winger Paul J. Rozance Russell V. Anthony |
| author_sort | Taylor K. Hord |
| collection | DOAJ |
| description | While 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) stimulate fetal growth and 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 the 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 (<i>p</i> ≤ 0.05), while umbilical blood flow (<i>p</i> ≤ 0.01), both uterine and umbilical glucose and oxygen uptakes (<i>p</i> ≤ 0.05), and umbilical concentrations of insulin and IGF1 (<i>p</i> ≤ 0.05) were reduced in CSH RNAi PI-FGR pregnancies. Fetal cotyledon <i>IGF1</i> mRNA concentration was reduced (<i>p</i> ≤ 0.05) in CSH RNAi PI-FGR pregnancies, whereas neither <i>IGF1</i> nor <i>IGF2</i> mRNA concentrations were impacted in the maternal caruncles, and either placental tissue in the non-FGR pregnancies. Fetal cotyledon <i>IGF1R</i> and <i>IGF2R</i> mRNA concentrations were not impacted for either phenotype, yet <i>IGF2R</i> was increased (<i>p</i> ≤ 0.01) in the maternal caruncles of CSH RNAi PI-FGR pregnancies. For the IGF binding proteins (IGFBP1, IGFBP2, IGFBP3), only <i>IGFBP2</i> mRNA concentrations were impacted, with elevated <i>IGFBP2</i> mRNA in both the fetal cotyledon (<i>p</i> ≤ 0.01) and maternal caruncle (<i>p</i> = 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. |
| first_indexed | 2024-03-11T02:14:32Z |
| format | Article |
| id | doaj.art-84a1be9fd78740e28c2bccebd1c17409 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-11T02:14:32Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-84a1be9fd78740e28c2bccebd1c174092023-11-18T11:16:50ZengMDPI AGLife2075-17292023-05-01136126110.3390/life13061261Impact of Chorionic Somatomammotropin In Vivo RNA Interference Phenotype on Uteroplacental Expression of the IGF AxisTaylor K. Hord0Amelia R. Tanner1Victoria C. Kennedy2Cameron S. Lynch3Quinton A. Winger4Paul J. Rozance5Russell V. Anthony6College of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USACollege of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USACollege of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USACollege of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USACollege of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USAAnschutz Medical Campus, University of Colorado School of Medicine, Aurora, CO 80045, USACollege of Veterinary Medicine, Colorado State University, Fort Collins, CO 80523, USAWhile 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) stimulate fetal growth and 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 the 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 (<i>p</i> ≤ 0.05), while umbilical blood flow (<i>p</i> ≤ 0.01), both uterine and umbilical glucose and oxygen uptakes (<i>p</i> ≤ 0.05), and umbilical concentrations of insulin and IGF1 (<i>p</i> ≤ 0.05) were reduced in CSH RNAi PI-FGR pregnancies. Fetal cotyledon <i>IGF1</i> mRNA concentration was reduced (<i>p</i> ≤ 0.05) in CSH RNAi PI-FGR pregnancies, whereas neither <i>IGF1</i> nor <i>IGF2</i> mRNA concentrations were impacted in the maternal caruncles, and either placental tissue in the non-FGR pregnancies. Fetal cotyledon <i>IGF1R</i> and <i>IGF2R</i> mRNA concentrations were not impacted for either phenotype, yet <i>IGF2R</i> was increased (<i>p</i> ≤ 0.01) in the maternal caruncles of CSH RNAi PI-FGR pregnancies. For the IGF binding proteins (IGFBP1, IGFBP2, IGFBP3), only <i>IGFBP2</i> mRNA concentrations were impacted, with elevated <i>IGFBP2</i> mRNA in both the fetal cotyledon (<i>p</i> ≤ 0.01) and maternal caruncle (<i>p</i> = 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.https://www.mdpi.com/2075-1729/13/6/1261placentaCSHRNA interferencefetal growth restrictionIGF1IGF2 |
| spellingShingle | Taylor K. Hord Amelia R. Tanner Victoria C. Kennedy Cameron S. Lynch Quinton A. Winger Paul J. Rozance Russell V. Anthony Impact of Chorionic Somatomammotropin In Vivo RNA Interference Phenotype on Uteroplacental Expression of the IGF Axis Life placenta CSH RNA interference fetal growth restriction IGF1 IGF2 |
| title | Impact of Chorionic Somatomammotropin In Vivo RNA Interference Phenotype on Uteroplacental Expression of the IGF Axis |
| title_full | Impact of Chorionic Somatomammotropin In Vivo RNA Interference Phenotype on Uteroplacental Expression of the IGF Axis |
| title_fullStr | Impact of Chorionic Somatomammotropin In Vivo RNA Interference Phenotype on Uteroplacental Expression of the IGF Axis |
| title_full_unstemmed | Impact of Chorionic Somatomammotropin In Vivo RNA Interference Phenotype on Uteroplacental Expression of the IGF Axis |
| title_short | Impact of Chorionic Somatomammotropin In Vivo RNA Interference Phenotype on Uteroplacental Expression of the IGF Axis |
| title_sort | impact of chorionic somatomammotropin in vivo rna interference phenotype on uteroplacental expression of the igf axis |
| topic | placenta CSH RNA interference fetal growth restriction IGF1 IGF2 |
| url | https://www.mdpi.com/2075-1729/13/6/1261 |
| work_keys_str_mv | AT taylorkhord impactofchorionicsomatomammotropininvivornainterferencephenotypeonuteroplacentalexpressionoftheigfaxis AT ameliartanner impactofchorionicsomatomammotropininvivornainterferencephenotypeonuteroplacentalexpressionoftheigfaxis AT victoriackennedy impactofchorionicsomatomammotropininvivornainterferencephenotypeonuteroplacentalexpressionoftheigfaxis AT cameronslynch impactofchorionicsomatomammotropininvivornainterferencephenotypeonuteroplacentalexpressionoftheigfaxis AT quintonawinger impactofchorionicsomatomammotropininvivornainterferencephenotypeonuteroplacentalexpressionoftheigfaxis AT pauljrozance impactofchorionicsomatomammotropininvivornainterferencephenotypeonuteroplacentalexpressionoftheigfaxis AT russellvanthony impactofchorionicsomatomammotropininvivornainterferencephenotypeonuteroplacentalexpressionoftheigfaxis |