IGF2 May Enhance Placental Fatty Acid Metabolism by Regulating Expression of Fatty Acid Carriers in the Growth of Fetus and Placenta during Late Pregnancy in Pigs

Zhimin Wu; Guangling Hu; Yiyu Zhang; Zheng Ao

doi:10.3390/genes14040872

IGF2 May Enhance Placental Fatty Acid Metabolism by Regulating Expression of Fatty Acid Carriers in the Growth of Fetus and Placenta during Late Pregnancy in Pigs

Genes (Basel). 2023 Apr 5;14(4):872. doi: 10.3390/genes14040872.

Authors

Zhimin Wu^{1

2}, Guangling Hu^{1

2}, Yiyu Zhang^{1

2}, Zheng Ao^{1

2}

Affiliations

¹ Key Laboratory of Animal Genetics, Breeding and Reproduction in the Plateau Mountainous Region, Ministry of Education, College of Animal Science, Guizhou University, Guiyang 550025, China.
² Guizhou Provincial Key Laboratory of Animal Genetics, Breeding and Reproduction, College of Animal Science, Guizhou University, Guiyang 550025, China.

Abstract

Fatty acids (FAs) are essential substances for the growth and development of the fetus and placenta. The growing fetus and placenta must obtain adequate FAs received from the maternal circulation and facilitated by various placental FA carriers, including FA transport proteins (FATPs), FA translocase (FAT/CD36), and cytoplasmic FA binding proteins (FABPs). Placental nutrition transport was regulated by imprinted genes H19 and insulin-like growth factor 2 (IGF2). Nevertheless, the relationship between the expression patterns of H19/IGF2 and placental fatty acid metabolism throughout pig pregnancy remains poorly studied and unclear. We investigated the placental fatty acid profile, expression patterns of FA carriers, and H19/IGF2 in the placentae on Days 40 (D40), 65 (D65), and 95 (D95) of pregnancy. The results showed that the width of the placental folds and the number of trophoblast cells of D65 placentae were significantly increased than those of D40 placentae. Several important long-chain FAs (LCFAs), including oleic acid, linoleic acid, arachidonatic acid, eicosapentaenoic acid, and docosatetraenoic acid, in the pig placenta showed dramatically increased levels throughout pregnancy. The pig placenta possessed higher expression levels of CD36, FATP4, and FABP5 compared with other FA carriers, and their expression levels had significantly upregulated 2.8-, 5.6-, and 12.0-fold from D40 to D95, respectively. The transcription level of IGF2 was dramatically upregulated and there were corresponding lower DNA methylation levels in the IGF2 DMR2 in D95 placentae relative to D65 placentae. Moreover, in vitro experimentation revealed that the overexpression of IGF2 resulted in a significant increase in fatty acid uptake and expression levels of CD36, FATP4, and FABP5 in PTr2 cells. In conclusion, our results indicate that CD36, FATP4, and FABP5 may be important regulators that enhance the transport of LCFAs in the pig placenta and that IGF2 may be involved in FA metabolism by affecting the FA carriers expression to support the growth of the fetus and placenta during late pregnancy in pigs.

Keywords: DNA methylation; IGF2; fatty acid carriers; pig; placenta.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carrier Proteins / genetics
DNA Methylation
Fatty Acids* / metabolism
Female
Fetus / metabolism
Placenta* / metabolism
Pregnancy
Swine
Trophoblasts / metabolism

Substances

Fatty Acids
Carrier Proteins

Grants and funding

This study was supported by two grants received from the Department of Science and Technology of Guizhou Province, China (No. QKHJC-ZK [2021]YB166 and No. QKHZC [2021]YB147), one grant received from the China Scholarship Council (No. LJM [2021]109), the Youth Science and Technology talent Development Project of Education Department of Guizhou Province, China (No. QJHKYZ [2021]081), the Guizhou Outstanding Young Scientific and Technological Talents Training Program (No. QKHPTR2C [2021]5630).