# The effect of norethisterone acetate on the uterine telocytes, immune cells and progesterone receptors in albino rats

**Authors:** Mahmoud Abd-Elkareem, Sulaiman Mohammed Alnasser, Alotaibi Meshal, Mohamed H. Kotob, Ayman S. Amer, Raghda Ismail Abdullah, Ahmed U. Ali

PMC · DOI: 10.1038/s41598-025-92354-5 · 2025-03-15

## TL;DR

This study explores how norethisterone acetate affects immune cells and uterine cells in rats, shedding light on its contraceptive mechanism.

## Contribution

This is the first study to investigate NETA's effects on telocytes, immune cells, and progesterone receptors in the uterus.

## Key findings

- NETA increases infiltration and activity of immune cells like eosinophils and neutrophils.
- NETA enhances telocyte vesicular activity and communication with immune cells.
- NETA influences decidualization and progesterone receptor immunoexpression in uterine cells.

## Abstract

This study is the first attempt to examine the effects of NETA on immune cells and telocytes. The results of this study form an important knowledge base for the development of new information on the mechanism of contraceptive action of NETA in the uterus. Norethisterone acetate (NETA) is a synthetic progestogen medication commonly utilized in birth control pills, menopausal hormone therapy, and for curing abnormal uterine bleeding and endometriosis. Furthermore NETA has many beneficial uses in veterinary medicine as control and synchronization of estrous cycle. The impact of NETA on the endometrial stromal cells (ESCs), telocytes, and uterine immune cells is not well understood. Therefore, this study focuses on assessing changes in uterine immune cells, ESCs, and telocytes following exposure to NETA in albino rats. To achieve this objective, fourteen adult female albino rats were randomly divided into two groups: a control group and an NETA-treated group. Rats in the control group received daily pelleted food, water, and were oral administered of 2 ml distilled water. In contrast, rats in the NETA-treated group received daily pelleted food, water, and were orally administered 20 µg of NETA dissolved in 2 ml distilled water. The experiment spanned three weeks. The findings of this study revealed that NETA usage increases the infiltration and activity of immune cells (eosinophils, neutrophils, macrophages, lymphocytes, and mast cells). Furthermore, it enhances the vesicular activity of uterine telocytes and their communication with various immune cells. NETA also influences decidualization and the immunoexpression of progesterone receptors in uterine epithelial and immune cells. This study concludes that the primary mechanism by which NETA controls pregnancy is through decidual (pregnancy-like) effects or improper decidualization, which inhibits fertilization and implantation respectively. Our research provides evidence of the contraceptive mechanism of NETA from an immunological perspective in an animal model.

## Linked entities

- **Chemicals:** norethisterone acetate (PubChem CID 5832), NETA (PubChem CID 169245)
- **Diseases:** endometriosis (MONDO:0005133)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Diseases:** endometriosis (MESH:D004715), abnormal uterine bleeding (MESH:D014592)
- **Chemicals:** NETA (MESH:D000077563)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11910565/full.md

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Source: https://tomesphere.com/paper/PMC11910565