# Primate-specific miRNAs in Embryonic and Placental Development

> **NIH NIH K99** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $45,494

## 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 perturb C19MC expression to evaluate
the impact of aberrant C19MC miRNA expression on embryo development and primate placentation. This Aim
will 1) repress and overexpress C19MC cluster and individual C19MC miRNAs expression in TSCs, 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 as well as 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:** 10405364
- **Project number:** 3K99HD099154-02S1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Jenna Ann Schmidt
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $45,494
- **Award type:** 3
- **Project period:** 2021-08-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405364

## Citation

> US National Institutes of Health, RePORTER application 10405364, Primate-specific miRNAs in Embryonic and Placental Development (3K99HD099154-02S1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10405364. Licensed CC0.

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