# Mechanisms and impact of pregnancy-induced adaptations in pelvic floor muscles

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $321,625

## Abstract

PROJECT SUMMARY
Maternal childbirth injury is the leading risk factor for pelvic floor muscle (PFM) dysfunction and the resultant
pelvic floor disorders. Despite this, individualized risk assessment prior to delivery is currently not possible and
the impact of PFM birth injury on the functionally relevant muscle components is not well defined. As a result,
there are no preventative strategies beyond Cesarean section and available treatments are severely limited.
Using the rat model, we recently discovered the existence of pregnancy-induced adaptations in the PFMs,
specifically fiber elongation via serial addition of sarcomeres, or sarcomerogenesis, and changes in
extracellular matrix (ECM) content and muscle stiffness. These important discoveries led to our overall
hypotheses that 1) pregnancy-induced adaptations prepare PFMs to withstand the mechanical demands
associated with parturition, and 2) when these adaptations are either deficient or are exceeded, injury to the
PFMs ensues. We will test these hypotheses in 3 independent but interrelated Aims, using the rat model. Aim
1 will focus on determining the protective effect of PFM pregnancy-induced adaptations against mechanical
injury and the impact of birth injury on postpartum muscle recovery. Using late-pregnant, non-pregnant, and
mid-pregnant rats, we will determine the acute and long-term response of the PFMs to strains, when
pregnancy-induced adaptations are either present, absent, or incomplete. Aim 2 will focus on the mechanisms
that drive pregnancy-induced adaptations in the PFMs, with the hypothesis that greater mechanical load from
the enlarged uterus, combined with hormonal milieu of pregnancy, lead to sarcomerogenesis, increased ECM
content, and higher muscle stiffness. To determine the independent and combined effects of mechanical and
endocrine cues associated with pregnancy on PFM plasticity, we will use unilaterally pregnant rats and a novel
non-pregnant rat model with unilaterally weight-loaded uterine horns. Aim 3 will test whether relaxin, a critical
pregnancy hormone that has been speculated to regulate sarcomerogenesis and intramuscular ECM
remodeling, is necessary for pregnancy-induced adaptations in the PFMs. We will neutralize endogenous
relaxin in pregnant rats and assess the influence of relaxin deprivation on the contractile, ECM, and cellular
components of the PFMs. We will then administer relaxin to non-pregnant animals with and without weight
loaded uterine horns, to test whether relaxin is sufficient to drive PFM adaptations alone or in conjunction with
increased mechanical load. Together, these Aims will elucidate the impact of pregnancy and delivery on PFM
mechanical, adaptive and regenerative properties. The results of these innovative experiments will serve as a
framework for the development of novel strategies for maximizing protective adaptations and regeneration in
pelvic floor muscles. If successful, such strategies could shift the current clinical paradi...

## Key facts

- **NIH application ID:** 9923711
- **Project number:** 5R01HD092515-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Marianna Alperin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $321,625
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923711

## Citation

> US National Institutes of Health, RePORTER application 9923711, Mechanisms and impact of pregnancy-induced adaptations in pelvic floor muscles (5R01HD092515-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9923711. Licensed CC0.

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