# The role of SMAD1 and SMAD5 in hormonal response, endometrial receptivity and glandular function

> **NIH NIH R00** · BAYLOR COLLEGE OF MEDICINE · 2021 · $234,793

## Abstract

Project Summary
Despite the high incidence of early pregnancy loss among women, its causes are not well-understood and the
treatment options are limited. The endometrium is the first site of contact between the embryo and
mother, therefore, understanding the molecular signature of the endometrium at the time of embryo
implantation will help us develop therapies to prevent early pregnancy loss in women. Bone
morphogenetic proteins (BMPs) are highly conserved factors of the TGFb superfamily that signal by binding to
a heterodimeric receptor complex composed of a BMP type 1 receptor and type 2 receptor complex. After
receptor binding and activation, SMAD1 and SMAD5 proteins are phosphorylated, form a complex with
SMAD4, and translocate to the nucleus to control gene expression. We recently showed that signaling
components of the TGFb family (ALK3, ALK5, BMP7 and follistatin) are critical for endometrial receptivity by
controlling the endometrial response to the steroid hormones, estrogen (E2) and progesterone (P4). However,
the mechanism linking the TGFb pathway and the endometrial response to the steroid hormones is not
understood. The goals of this proposal are to determine how the downstream signaling components of the
BMP pathway, the SMAD1 and SMAD5 transcription factors, control the response to E2 and P4 in the
endometrium during the process of embryo implantation. We will use transgenic mice and human endometrial
samples to fully delineate how SMAD1 and SMAD5 control the endometrial response to E2 and P4 during
early pregnancy. This award will support the career development of Diana Monsivais, Ph.D., a Postdoctoral
Associate and IRACDA Fellow at Baylor College of Medicine. The candidate will be co-mentored by Dr. Martin
Matzuk, the Stuart A. Wallace Chair, Robert L. Moody, Sr. Chair, and Professor in the Dept. of Pathology &
Immunology at Baylor College of Medicine and by Dr. Masahito Ikawa, Distinguished Professor at the
Research Institute for Microbial Diseases in Osaka University. Both co-mentors are outstanding researchers in
the fields of reproduction and mouse genetics. The research will be primarily performed in Dr. Matzuk’s
laboratory at Baylor College of Medicine, a top research institution in the Texas Medical Center, providing Dr.
Monsivais with abundant research resources and access to collaborations. In the short-term, the award will
provide Dr. Monsivais with career development and research training in reproductive biology and mouse
genetics. In the long-term, this award will support the candidate’s transition into a faculty position as an
independent investigator. Data from these studies will reveal the molecular events that orchestrate maternal
and embryonic interactions during implantation, and will improve the therapeutic options for women
experiencing infertility and early pregnancy loss.

## Key facts

- **NIH application ID:** 10212434
- **Project number:** 5R00HD096057-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Diana Monsivais
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $234,793
- **Award type:** 5
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212434

## Citation

> US National Institutes of Health, RePORTER application 10212434, The role of SMAD1 and SMAD5 in hormonal response, endometrial receptivity and glandular function (5R00HD096057-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10212434. Licensed CC0.

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