Chorionic somatomammotropin RNA interference alters fetal liver glucose utilization

in Journal of Endocrinology
Authors:
Asghar Ali Colorado State University, Animal Reproduction and Biotechnology Lab, Fort Collins, Colorado, USA

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Callie M Swanepoel Colorado State University, Animal Reproduction and Biotechnology Lab, Fort Collins, Colorado, USA

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Quinton A Winger Colorado State University, Animal Reproduction and Biotechnology Lab, Fort Collins, Colorado, USA

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Paul J Rozance Perinatal Research Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

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Russell V Anthony Colorado State University, Animal Reproduction and Biotechnology Lab, Fort Collins, Colorado, USA

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Correspondence should be addressed to R V Anthony: russ.anthony@colostate.edu
DOI:
https://doi.org/10.1530/JOE-20-0375
Volume/Issue:
Volume 247: Issue 3
Article Type:
Research Article
Page Range:
251–262
Online Publication Date:
Dec 2020
Copyright:
© 2020 Society for Endocrinology 2020
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Chorionic somatomammotropin (CSH) is a placenta-specific hormone associated with fetal growth, and fetal and maternal metabolism in both humans and sheep. We hypothesized that CSH deficiency could impact sheep fetal liver glucose utilization. To generate CSH-deficient pregnancies, day 9 hatched blastocysts were infected with lentiviral particles expressing CSH-specific shRNA (RNAi) or scramble control shRNA (SC) and transferred to synchronized recipients. CSH RNAi generated two distinct phenotypes at 135 days of gestational age (dGA); pregnancies with IUGR (RNAi-IUGR) or with normal fetal weight (RNAi-NW). Fetal body, fetal liver and placental weights were reduced (P < 0.05) only in RNAi-IUGR pregnancies compared to SC. Umbilical artery plasma insulin and insulin-like growth factor 1 (IGF1) concentrations were decreased, whereas insulin receptor beta (INSR) concentration in fetal liver was increased (P < 0.05) in both RNAi phenotypes. The mRNA concentrations of IGF1, IGF2, IGF binding protein 2 (IGFBP2) and IGFBP3 were decreased (P < 0.05) in fetal livers from both RNAi phenotypes. Fetal liver glycogen concentration and glycogen synthase 1 (GYS1) concentration were increased (P < 0.05), whereas fetal liver phosphorylated-GYS (inactive GYS) concentration was reduced (P < 0.05) in both RNAi phenotypes. Lactate dehydrogenase B (LDHB) concentration was increased (P < 0.05) and IGF2 concentration was decreased (P < 0.05) in RNAi-IUGR fetal livers only. Our findings suggest that fetal liver glucose utilization is impacted by CSH RNAi, independent of IUGR, and is likely tied to enhanced fetal liver insulin sensitivity in both RNAi phenotypes. Determining the physiological ramifications of both phenotypes, may help to differentiate direct effect of CSH deficiency or its indirect effect through IUGR.

Supplementary Materials

    • Supplementary table 1. Antibodies

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
12
Article Type:
Research Article
Received Date:
21 Aug 2020
Accepted Date:
22 Sep 2020
Print Publication Date:
01 Dec 2020
Online Publication Date:
Dec 2020
Keywords:
chorionic somatomammotropin; glycogen; insulin receptor; glycogen synthase

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