The short reproductive cycle length observed in rodents, called the estrous cycle, makes them an ideal animal model for investigation of changes that occur during the reproductive cycle. Most of the data in the literature about the estrous cycle is obtained from rat because they are easily manipulated and exhibit a clear and well defined estrous cycle. However, the increased number of experiments using knockout mice requires identification of their estrous cycle as well, since (in)fertility issues may arise. In mice, like rats, the identification of the stage of estrous cycle is based on the proportion of cells types observed in the vaginal secretion. The aim of this unit is to provide guidelines for quickly and accurately determining estrous cycle phases in mice.
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Estrous cycle; mouse; vaginal smears; wet vaginalIn humans, the reproductive cycle, called the menstrual cycle, lasts approximately 28 days, in rodents this cycle, called the estrous cycle, lasts approximately 4-5 days. The success of reproduction in all mammals depends on the function of the hypothalamus-pituitary-gonads axis. In females, gonadotropin-releasing hormone (GnRH) neurons present in the septal area and hypothalamus send their axons to median eminence. GnRH released there reaches the anterior pituitary where the gonadotrophs are stimulated to secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In the peripheral circulation, these hormones stimulate specific cells in the ovary leading to ovulation. Ovarian follicles secrete estrogen (E2) that reaches the hypothalamus. Most of the time, the plasma concentration of E2 is low. However, during the pre-ovulatory period E2 secretion reaches a peak, and GnRH neurons are stimulated (Sarkar et al., 1976;Freeman, 1994). E2 seems to regulate GnRH neurons indirectly, via interneurons. However, there are many questions needing to be answered in this field. Importantly, because E2 has a myriad of effects, questions are raised not only in the neuroendocrine field, but also in the neurosciences (e.g. synaptic plasticity, memory and learning and neurodegenerative diseases) as well as fields studying cardiological and/or renal function, sodium and water equilibrium, etc.A short cycle length makes rodents an ideal animal model for investigating changes occurring during the reproductive cycle and historically rats have been the chosen model. Rats display, most of time, regular cycles; they are easy to manipulate; and the cycle is not disrupted easily even with the routine stress in the animal facility. However, as use of mice lines continues to increase, an understanding of the mouse estrous cycle is critical for investigators and in fact many knockout mice can exhibit puberty/fertility changes that can effect, simply, maintaining a knockout line. There are few published studies involving estrous cycle in mice. The stages of the estrous cycle are not as visually discernible as in rats, and handling mice requires more caution due to their aggressive behavior. M...