Rodent estrous cycle pattern: Harmonizing the cycle evaluation and interpretation.

Area of Science:

• Reproductive toxicology
• Endocrinology
• Animal models

Background:

• The estrous cycle is a key indicator in reproductive toxicity studies, particularly for assessing endocrine disruptors.
• Current methods for estrous cycle timing show discrepancies among testing laboratories.

Purpose of the Study:

• To review methods for estrous cycle timing and evaluation in rodent reproductive toxicity studies.
• To identify and address inconsistencies in estrous cycle counting, particularly concerning extended estrus stages.

Main Methods:

• Review of existing literature and testing laboratory protocols for estrous cycle evaluation.
• Analysis of discrepancies in cycle counting, focusing on extended estrus (E) and proestrus (P) phases.

Main Results:

• No significant differences were found in counting standard 4-day estrous cycles.
• Discrepancies arise when extended episodes of estrus occur, leading to potential misinterpretation of results.
• Current OECD guidance may be unclear for 5-day cycles involving extended estrus stages.

Conclusions:

• Standardization of estrous cycle counting is needed, especially for 4/5-day cycles with extended estrus.
• Recommendations include updating OECD guidance and defining abnormal cycle patterns (e.g., two E after P, three consecutive E).
• Collaboration is encouraged to harmonize estrous cycle counting approaches for reliable toxicity assessments.