# Function of TRPML1 in uterine luminal fluid resorption

> **NIH NIH R03** · UNIVERSITY OF GEORGIA · 2021 · $75,500

## Abstract

Project Summary / Abstract:
 Defective uterine function for embryo implantation is associated with two major public
health problems in reproductive women, infertility and early pregnancy loss. How a uterus
transiently transforms into a receptive state (uterine receptivity) for embryo implantation is the
least well understood step during pregnancy. Uterine epithelium is the first maternal contact for
an implanting embryo. Our novel finding of uterine epithelial lysosomal acidification upon
embryo implantation led us to the investigation of lysosomes in the establishment of uterine
receptivity. Lysosomal acidity regulates lysosomal activities in essential cellular processes, such
as vesicular trafficking in endocytosis and exocytosis. Lysosomal acidity is maintained by V-
ATPase and counter ion channels. Our preliminary data demonstrate prominent expression of
TRPML1 (a counter ion channel encoded by MCOLN1) in the uterine epithelium and defective
embryo implantation in 5 months old Mcoln1-/- mice, which have progesterone deficiency and
uterine luminal fluid retention that could not be alleviated by exogenous progesterone treatment.
Mutations of MCOLN1 in human and mouse cause mucolipidosis type IV, a severe lysosomal
disorder, indicating a critical role of TRPML1 in lysosomal functions. The mechanisms of
TRPML1 in uterine fluid resorption to facilitate uterine lumen closure and embryo implantation
remain as a significant knowledge gap. Our long-term goal is to understand the mechanisms
involved in the establishment of uterine receptivity thus help overcome infertility and early
pregnancy loss associated with defective uterine receptivity. The defined objective of this R03
application is to determine a cellular mechanism of TRPML1 in uterine fluid resorption, a
prerequisite for the establishment of uterine receptivity. Our central hypothesis is that TRPML1
regulates lysosomal function in endocytosis to absorb uterine luminal fluid for uterine lumen
closure and subsequent embryo implantation. It will be tested in the following two specific aims
using a Mcoln1-/- mouse model. Aim 1. Determine uterine epithelial lysosomal activity in
preimplantation Mcoln1-/- uterus. Aim 2. Determine uterine epithelial endocytosis in
preimplantation Mcoln1-/- uterus. Ovariectomy, ovarian hormone injection, tracer injection,
immunofluorescence, and transmission electron microscopy are among the approaches that will
be employed. The proposed work is significant for advancing our understanding of the
mechanisms in the establishment of uterine receptivity as well as for providing knowledge to
develop diagnostic and therapeutic approaches for infertility and early pregnancy loss, which is
a high priority research area identified by NICHD.

## Key facts

- **NIH application ID:** 10067560
- **Project number:** 5R03HD100652-02
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Xiaoqin Ye
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $75,500
- **Award type:** 5
- **Project period:** 2019-12-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10067560

## Citation

> US National Institutes of Health, RePORTER application 10067560, Function of TRPML1 in uterine luminal fluid resorption (5R03HD100652-02). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10067560. Licensed CC0.

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