# Primate-specific miRNAs in Embryonic and Placental Development

> **NIH NIH K99** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $91,031

## Abstract

PROJECT ABSTRACT
Placental pathologies stem from poor early placental development characterized by shallow invasion of
trophoblasts, and are also associated with aberrant expression of miRNAs belonging to the primate-specific
chromosome 19 miRNA cluster (C19MC). C19MC miRNAs are thought to have roles in trophoblast invasion and
migration, however, their role(s) in primate embryonic and early placental development is not well-defined. I
hypothesize that C19MC miRNAs will have primate-specific roles in trophectoderm lineage specification
and early development of the primate placenta. The overall objective of my proposal is to determine the role
of these miRNAs in primate trophoblast lineage specification and placental development in a rhesus macaque
model, and reveal gene networks regulated by miRNAs in primate placentation. Towards this objective, I propose
three Specific Aims.
Specific Aim 1 (K99-phase). To define the expression of miRNAs in the primate embryo and
trophoblast stem cells (TSC). This aim will establish the miRNA signature during embryo development
through specification of the trophectoderm lineage and determine whether these miRNAs are
expressed in a stage- or cell-type-specific manner.
Specific Aim 2 (K99-phase). To determine the functional role(s) of C19MC members in TSC and
differentiated trophoblast function. This experiment will directly overexpress C19MC miRNA members
in TSC to identify genes and pathways regulated by these miRNAs, assessing their functional roles.
Specific Aim 3 (R00-phase). To use genome editing strategies to globally perturb the C19MC and
evaluate the impact of aberrant C19MC miRNA expression on embryo development and primate
placentation. This Aim will 1) repress and overexpress C19MC cluster expression utilizing genome
editing tools in TSC, 2) apply C19MC genome editing to embryos to evaluate the role of cluster
expression on primate preimplantation embryo development, and 3) determine the impact of embryonic
genome editing on trophectoderm function and differentiation in an in vitro implantation culture model.
I have recently developed macaque TSCs with methods described by Okae et al. (2018), and have experience
with rhesus IVF to derive embryos for genome editing and in vitro implantation experiments. TSC and embryo
resources will be used to define miRNA and mRNA expression during embryo development and trophoblast
lineage specification and identify miRNA-regulated gene networks in early placentation. Overall, the proposed
research will establish a basic understanding of miRNA expression and miRNA target gene regulation in the
embryo to placenta transition. Ultimately, we envision that the nonhuman primate model will allow us to extend
these approaches to transfer of edited embryos to recipient dams, and to develop in vivo strategies to directly
target the placenta for modification of miRNA expression for experimental and therapeutic purposes.

## Key facts

- **NIH application ID:** 9984891
- **Project number:** 5K99HD099154-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Jenna Ann Schmidt
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $91,031
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984891

## Citation

> US National Institutes of Health, RePORTER application 9984891, Primate-specific miRNAs in Embryonic and Placental Development (5K99HD099154-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984891. Licensed CC0.

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