Primary endometrial 3D co-cultures: A comparison between human and rat endometrium

Area of Science:

• Reproductive biology
• Toxicology
• Endocrinology

Background:

• Human and rat reproductive systems exhibit significant differences in hormonal cyclicity and endometrial cell behavior.
• Species-specific responses of endometrial cells to hormonal stimulation and toxic compounds are not well understood.

Purpose of the Study:

• To investigate and compare in vitro endometrial cell responses to hormonal treatments and aryl hydrocarbon receptor (AHR) ligands in human and rat models.
• To assess species differences in endometrial responses relevant for toxicological risk assessment.

Main Methods:

• Utilized a 3D co-culture model of primary human and rat endometrial cells.
• Exposed models to hormonal treatments and AHR ligands: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), laquinimod, and its metabolite DELAQ.
• Assessed gene expression of estrogen receptor, progesterone receptor, AHR, and cytochrome P450 1A1 (CYP1A1).

Main Results:

• Hormonal treatments modulated estrogen and progesterone receptor gene expression similarly in both human and rat models.
• Aryl hydrocarbon receptor (AHR) gene expression decreased with progesterone in rat models, attenuating TCDD's induction of CYP1A1.
• TCDD and DELAQ induced CYP1A1 gene expression in both species, with DELAQ showing a higher relative induction in the human model compared to the rat model.

Conclusions:

• Significant species-specific differences exist in human and rat endometrial cell responses to hormones and AHR ligands in vitro.
• The rat may not be an ideal translational model for human endometrial effects, particularly concerning AHR ligand toxicity.
• Further development of human-relevant, endometrium-specific test methods is warranted for accurate risk assessment.