# The role of Neuregulin-1 (NRG1) in corpus luteum (CL) physiology

> **NIH NIH SC1** · MOREHOUSE SCHOOL OF MEDICINE · 2020 · $355,000

## Abstract

PROJECT SUMMARY/ABSTRACT
The role of Neuregulin-1 (NRG1) in corpus luteum (CL) physiology
Formation of a functional corpus luteum (CL) is an absolute requirement for reproductive success and is induced by the
mid-cycle surge of luteinizing hormone (LH). The CL is a transient ovarian endocrine structure that maintains pregnancy
in primate during the first trimester and in rodents during the entire pregnancy by the production of steroid hormone
progesterone (P4). CL defects contribute to decreasing P4 production and subsequent inability to support a developing
fetus and reproductive failures. CL growth and differentiation are tightly regulated by both survival and cell death signals,
including endocrine (LH), intra-ovarian regulators and cell-cell interactions. The interplay between the LH, P4 and
inflammatory markers have been well established in human and animal models. For maintaining pregnancy, luteal
establishment and development of highly vascularized CL upon fertilization, a plethora of pro-inflammatory and pro-
apoptotic factors are needed for tissue remodeling of the ovulated follicle. Whereas, to protect ovulated follicle and its
surrounding cells/tissues for the formation of a functional CL requires a plethora of pro-survival and anti-
inflammatory factors to fine-tune and counterbalance mechanism against pro-apoptotic and pro-inflammatory
factors to create a favorable environment to maintain CL differentiated state and stage. Previously our lab has
demonstrated that NRG1, a member of epidermal growth factor (EGF) family, is gonadotropin (follicle stimulating
hormone, FSH and LH) dependent differentially regulated in granulosa cells (GCs) and theca cells, and secreted in the
ovarian follicular fluid (FF) as a cellular survival factor. Other labs have demonstrated that NRG1 enhances amphiregulin
(AREG)-induced P4 production in GCs, and exerts an important regulatory role in oocyte meiotic maturation, and prevent
premature progression to the metaphase II (MII) stage that leads to abnormal fertilization and fertility. Our preliminary
studies detected LH dependent expression of NRG1 in rat luteal cells (LCs) and CL. Furthermore, our preliminary studies
also provided novel evidence that NRG1 plays an important role in LCs survival and inhibition of inflammatory cytokines
and chemokine secretion, and suggest a possible role in LCs maturation and differentiation, and, may act through an
autocrine and/or paracrine mechanism. The anti-inflammatory and pro-survival functions of NRG1 and its underlying
mechanism of action in LCs and CL functions are yet to be defined. Our long-term goal is to understand the physiological
role of NRG1 on CL differentiation through obtaining insights into its anti-inflammatory and pro-survival effect in
mechanistic detail. Thus, the central hypothesis to be tested in this proposal is that NRG1 is a critical cellular mediator
of LH stimulation of LCs, which supports CL function.

## Key facts

- **NIH application ID:** 9855327
- **Project number:** 1SC1GM130544-01A1
- **Recipient organization:** MOREHOUSE SCHOOL OF MEDICINE
- **Principal Investigator:** Indrajit Chowdhury
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $355,000
- **Award type:** 1
- **Project period:** 2020-09-10 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9855327

## Citation

> US National Institutes of Health, RePORTER application 9855327, The role of Neuregulin-1 (NRG1) in corpus luteum (CL) physiology (1SC1GM130544-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9855327. Licensed CC0.

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