# Molecular basis of spontaneous contraction in non-pregnant uterus

> **NIH NIH R21** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $209,375

## Abstract

Project Summary
The non-pregnant uterus generates peristalsis in a menstrual cycle dependent manner under the control of sex
hormones. This motility is a driving force to move menses, transport sperm and embryo, and regulate
implantation; hyper- or dysfunctional peristalsis has been linked to major gynecological and obstetric disorders
such as endometriosis and adenomyosis. However, the molecular mechanisms driving uterine peristalsis
remain unclear. With state-of-the-art two-photon imaging of Ca2+ signals in a novel precision-cut uterine slice
preparation, we found that myometrial cells generate highly active asynchronous Ca2+ oscillations (ACaOs)
and synchronous Ca2+ oscillations (SCaOs) in an extracellular Ca2+ dependent manner. At the whole slice
level, we further found that they generate rhythmic contraction consisting of a phasic component added to a
basal tone, each dependent on extracellular Ca2+. Moreover, a T-type channel blocker inhibits ACaOs but not
ScaOs; an L-type channel blocker and a TMEM16A (Cl- channel) antagonist inhibit SCaOs but not ACaOs. In
light of the isoform expression levels and biophysics of the aforementioned three channels in uterus, we
hypothesize that the Cav3.2 T type channel is responsible for ACaOs and basal tone, and the interplay of
Cav1.2 and TMEM16A generates SCaOs and phasic contraction. To test and establish these hypotheses, we
will fully characterize ACaOs and SCaOs with two-photon imaging of uterine slices. Mice with smooth muscle
specific deletion of TMEM16A or Cav1.2 and systemic deletion of Cav3.2 will be used to firmly establish the
role each channel plays in these Ca2+ events and in force generation. This study will establish the ACaOs and
SCaOs as two key signals responsible for uterine peristalsis and identify the gene(s) for each component. The
outcome of this study will establish the basis to target genes in myometrial cells for new treatments for
reproduction disorders such as endometriosis and adenomyosis.

## Key facts

- **NIH application ID:** 9994367
- **Project number:** 5R21HD097458-02
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Ronghua ZhuGe
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $209,375
- **Award type:** 5
- **Project period:** 2019-08-12 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994367

## Citation

> US National Institutes of Health, RePORTER application 9994367, Molecular basis of spontaneous contraction in non-pregnant uterus (5R21HD097458-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9994367. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*