Chorionic Somatomammotropin RNA Interference Alters Fetal Liver Glucose Utilization

Overview

Journal J Endocrinol

Specialty Endocrinology

Date 2020 Oct 27

PMID 33108344

Citations 9

Authors

Asghar Ali

Callie M Swanepoel

Quinton A Winger

Paul J Rozance

Russell V Anthony

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Increasing maternal glucose concentrations is insufficient to restore placental glucose transfer in chorionic somatomammotropin RNA interference pregnancies.

Tanner A, Kennedy V, Lynch C, Winger Q, Anthony R, Rozance P Am J Physiol Endocrinol Metab. 2024; 326(5):E602-E615.

PMID: 38353640 PMC: 11376830. DOI: 10.1152/ajpendo.00331.2023.

Impact of Chorionic Somatomammotropin In Vivo RNA Interference Phenotype on Uteroplacental Expression of the IGF Axis.

Hord T, Tanner A, Kennedy V, Lynch C, Winger Q, Rozance P Life (Basel). 2023; 13(6).

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Evolution of Placental Hormones: Implications for Animal Models.

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In vivo investigation of ruminant placenta function and physiology-a review.

Tanner A, Kennedy V, Lynch C, Hord T, Winger Q, Rozance P J Anim Sci. 2022; 100(6).

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Hepatic IGF2/H19 Epigenetic Alteration Induced Glucose Intolerance in Gestational Diabetes Mellitus Offspring FoxO1 Mediation.

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