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Article

Trophectoderm-Specific Knockdown of LIN28 Decreases Expression of Genes Necessary for Cell Proliferation and Reduces Elongation of Sheep Conceptus

1
Department of Biomedical Sciences, Animal Reproduction and Biotechnology Laboratory, 1683 Campus Delivery, Colorado State University, Fort Collins, CO 80523, USA
2
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA
3
Animal Science Research Center, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, MO 65211, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(7), 2549; https://doi.org/10.3390/ijms21072549
Received: 13 March 2020 / Revised: 2 April 2020 / Accepted: 3 April 2020 / Published: 6 April 2020
(This article belongs to the Special Issue Embryo Implantation and Placental Development)
LIN28 inhibits let-7 miRNA maturation which prevents cell differentiation and promotes proliferation. We hypothesized that the LIN28-let-7 axis regulates proliferation-associated genes in sheep trophectoderm in vivo. Day 9-hatched sheep blastocysts were incubated with lentiviral particles to deliver shRNA targeting LIN28 specifically to trophectoderm cells. At day 16, conceptus elongation was significantly reduced in LIN28A and LIN28B knockdowns. Let-7 miRNAs were significantly increased and IGF2BP1-3, HMGA1, ARID3B, and c-MYC were decreased in trophectoderm from knockdown conceptuses. Ovine trophoblast (OTR) cells derived from day 16 trophectoderm are a useful tool for in vitro experiments. Surprisingly, LIN28 was significantly reduced and let-7 miRNAs increased after only a few passages of OTR cells, suggesting these passaged cells represent a more differentiated phenotype. To create an OTR cell line more similar to day 16 trophectoderm we overexpressed LIN28A and LIN28B, which significantly decreased let-7 miRNAs and increased IGF2BP1-3, HMGA1, ARID3B, and c-MYC compared to control. This is the first study showing the role of the LIN28-let-7 axis in trophoblast proliferation and conceptus elongation in vivo. These results suggest that reduced LIN28 during early placental development can lead to reduced trophoblast proliferation and sheep conceptus elongation at a critical period for successful establishment of pregnancy. View Full-Text
Keywords: trophectoderm; placenta; cell proliferation; let-7 miRNAs; gene regulation trophectoderm; placenta; cell proliferation; let-7 miRNAs; gene regulation
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MDPI and ACS Style

Ali, A.; Stenglein, M.D.; Spencer, T.E.; Bouma, G.J.; Anthony, R.V.; Winger, Q.A. Trophectoderm-Specific Knockdown of LIN28 Decreases Expression of Genes Necessary for Cell Proliferation and Reduces Elongation of Sheep Conceptus. Int. J. Mol. Sci. 2020, 21, 2549. https://doi.org/10.3390/ijms21072549

AMA Style

Ali A, Stenglein MD, Spencer TE, Bouma GJ, Anthony RV, Winger QA. Trophectoderm-Specific Knockdown of LIN28 Decreases Expression of Genes Necessary for Cell Proliferation and Reduces Elongation of Sheep Conceptus. International Journal of Molecular Sciences. 2020; 21(7):2549. https://doi.org/10.3390/ijms21072549

Chicago/Turabian Style

Ali, Asghar, Mark D. Stenglein, Thomas E. Spencer, Gerrit J. Bouma, Russell V. Anthony, and Quinton A. Winger 2020. "Trophectoderm-Specific Knockdown of LIN28 Decreases Expression of Genes Necessary for Cell Proliferation and Reduces Elongation of Sheep Conceptus" International Journal of Molecular Sciences 21, no. 7: 2549. https://doi.org/10.3390/ijms21072549

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