Abstract
Puberty is a key developmental event whose primary regulatory mechanisms remain poorly understood. Precise dating of puberty is crucial for experimental (preclinical) studies on its complex neuroendocrine controlling networks. In female laboratory rodents, external signs of puberty, such as vaginal opening (VO) and epithelial cell cornification (i.e., first vaginal estrus, FE), are indirectly related to the maturational state of the ovary and first ovulation, which is the unequivocal marker of puberty. Whereas in rats, VO and FE are almost simultaneous with the first ovulation, these events are not so closely associated in mice. Moreover, external signs of puberty can be uncoupled with first ovulation in both species under certain experimental conditions. We propose herein the Pubertal Ovarian Maturation Score (Pub-score), as novel, reliable method to assess peripubertal ovarian maturation in rats and mice. This method is founded on histological evaluation of pre-pubertal ovarian maturation, based on antral follicle development, and the precise timing of first ovulation, by retrospective dating of maturational and regressive changes in corpora lutea. This approach allows exact timing of puberty within a time-window of at least two weeks after VO in both species, thus facilitating the identification and precise dating of advanced or delayed puberty under various experimental conditions.
Highlights
Puberty is a key developmental event whose primary regulatory mechanisms remain poorly understood
In a previous study, Safranski and co-workers aimed to analyze the relationship between vaginal opening (VO), FE and post-mating vaginal plug (VP) in mice; they reported that none of the animals had ovulated at the age of VO, only 15% did at the age of FE, whereas 91% had ovulated at the age of VP10
The data available indicate that while external signs, such as VO or FE, are useful to monitor the rise of estrogens associated to pubertal maturation, they may not be fully reliable for the precise timing of first ovulation in mice, even under physiological conditions
Summary
Puberty is a key developmental event whose primary regulatory mechanisms remain poorly understood. Several indirect signs of puberty, accessible via non- or minimally-invasive procedures, such as the age of vaginal opening (VO), of the first appearance of cornified epithelial cells in the vagina (i.e., first vaginal estrus; FE), or the presence of a vaginal plug (VP) after mating, have been used as external markers of puberty onset in laboratory rodents[6] Both VO and FE are indirect markers of puberty, as they are caused by the rise in estradiol levels during peripubertal period, associated to the first wave of follicular maturation, and can be induced in juvenile rats by estrogen administration[6]. The data available indicate that while external signs, such as VO or FE, are useful to monitor the rise of estrogens associated to pubertal maturation, they may not be fully reliable for the precise timing of first ovulation in mice, even under physiological conditions
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