# Investigating obesity and adiposity-induced alterations to the human endometrium

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $195,000

## Abstract

Obesity is a highly prevalent chronic disease that poses a significant public health risk. Almost 42% of US
adults are affected by obesity with women at higher risk for severe obesity than men (11.5 vs 6.9%). Obesity
has a significant and complex impact on reproduction and is associated with menstrual irregularities,
anovulation, decreased rates of natural pregnancy, miscarriage, and infertility. While there are several known
causes of infertility such as decreased ovarian reserve, male factor, and tubal disease, most require invasive
and expensive procedures to achieve pregnancy, and, unlike obesity, very few are modifiable. Obesity is
commonly associated with anovulation-related causes of infertility but has been shown to impact all levels of
the reproductive axis including the hypothalamus, pituitary, ovary, and endometrium. While there are far fewer
studies on the endometrium than on other tissues, there are data from both human primary cells and mouse
models of obesity that implicate the endometrium in obesity-related infertility, mostly through defects in
endometrial decidualization, the process by which the endometrium prepares itself for implantation in the
luteal-phase of the menstrual cycle. There are two fundamental obstacles that have limited the ability to
understand the link between obesity, endometrial function, and infertility : 1) lack of comprehensive
phenotyping isolating obesity from other co-occurring conditions that impact the endometrium such as PCOS
and 2) reliance solely on BMI to study obesity. While obesity is most often singularly defined as a body mass
index (BMI) of ≥30 kg/m2, the sole use of BMI to categorize obesity-associated risks fails to consider the
heterogeneity of the disease. The overall objective of this proposal is to assess the impact of obesity and
adiposity as assessed by multiple parameters on the luteal-phase endometrium. We will include a cohort of
extensively-phenotyped women allowing for disentanglement of commonly co-occurring endocrine and
metabolic disorders that have confounded prior studies. We hypothesize that obesity is associated with
modified endometrial transcription and cellular subpopulations resulting in an altered proteomic profile and
aberrant decidualization. To test this hypothesis, in aim 1 we perform single-nuclear sequencing (snRNA-seq)
on endometrial samples from women with and without obesity to comprehensively understand how pathologic
adiposity might influence alterations in cellular populations. In aim 2 we will perform liquid chromatography
mass-spectrometry (LC-MS) to assess for altered proteomic profiles. Finally, in aim 3 we will perform functional
endometrial assays to correlate transcriptomic and proteomic signatures with functional markers of endometrial
dysfunction. These pilot experiments will provide novel insight into the well-known association of obesity with
infertility and early pregnancy loss, guiding planning for large scale validation and mechanistic studi...

## Key facts

- **NIH application ID:** 10985393
- **Project number:** 1R21HD113812-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Saher Sue Hammoud
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $195,000
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985393

## Citation

> US National Institutes of Health, RePORTER application 10985393, Investigating obesity and adiposity-induced alterations to the human endometrium (1R21HD113812-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10985393. Licensed CC0.

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