The rodent model is used in a majority of research laboratories due to their high availability, relatively lower cost of care, and less demanding housing needs. Additionally, though not as genetically similar as the primate model, they retain 90% homology with humans, and their shortened reproductive cycle and gestation period affords them a larger number of offspring each year. The rat and mouse models are most common to the laboratory setting, and each species offers unique benefits to research in reproductive aging.

Rats and mice undergo estrous cycles, as opposed to menstrual cycles in humans. Thus the process by which reproductive aging occurs in rodents is sometimes called estropause, and it shares some similarities, as well as some differences, with human menopause. The rodent estrous cycle is four to five days long, consisting of four phases: proestrus, estrus, diestrus I (sometimes referred to as metestrus), and diestrus II (see Figure 43.2). In rodents, estrous cyclicity can be tracked by observing daily vaginal cytology. Through this methodology, researchers have determined that rodents begin to show irregular cycles at middle age (9-12 months), as defined by prolonged cycles, most commonly with additional days of cornified vaginal cells, interspersed with the normal four- to five-day rhythm. As aging occurs, these animals transition into an acyclic, anestrus status, in which persistent estrus is observed and ovulation has ceased (Rubin, 2000). In accordance with humans, rodents begin to show reproductive decline in middle-age. Prior to the loss of regular estrous cycles, rats show increased FSH and estrogen levels accompanied by an attenuation and delay of the LH surge (Rubin, 2000), similar to humans (Wise et al., 2002). As irregular cycles set in and progress to anestrus, progesterone levels decline, with estrogen levels remaining moderately elevated in rats (see Figure 43.3). This latter phenomenon is dissimilar to that in humans and mice, in which estrogen levels decline (Rubin, 2000).

Age-related changes to the pituitary have also been noted in rodents, with decreased sensitivity to GnRH stimulation, decreased GnRH receptor mRNA during the


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