This page introduces the estrous cycle of the female rat (taxon- rattus). The female rat is a spontaneously ovulating polyestrous mammal with rapid ovulation cycles occuring at 4 to 5 day intervals (except during pregnancy, pseudopregnancy, and lactation).
A recent paper (Hubscher etal., 2005) has described a modified Papanicolaou (PAP) smear procedure to distinguish the various stages of the estrous cycle.
Hubscher CH, Brooks DL, Johnson JR. A quantitative method for assessing stages of the rat estrous cycle. Biotech Histochem. 2005 Mar-Apr;80(2):79-87.
"The impact of gender and/or hormone variations on a wide variety of neural functions makes the choice between studying males or females (or both) of a given species difficult. Although female rats are widely used experimentally, few studies control for the stage of estrus. More detailed information about how to distinguish the various stages of the estrous cycle is needed. For the present study, vaginal smears were obtained once a day and stained using an adaptation of the Papanicolaou (PAP) procedure. Images are provided of unstained "wet" samples and the corresponding PAP stained smears illustrating the cellular profile for each stage of the cycle as well as post-ovariectomy. The different cell populations across the cycle were quantified and ratios determined to show trends between the predominant and other cell types in each stage of the estrous cycle. Both stained and unstained images and cell quantification data provide valuable guidelines for distinguishing the stages of the estrous cycle. "
Montes GS, Luque EH. Effects of ovarian steroids on vaginal smears in the rat. Acta Anat (Basel). 1988;133(3):192-9.
"A correspondence between the appearance of vaginal smears and the layers of the epithelium from which the cells had desquamated was established in untreated rats during the estrous cycle, in control ovariectomized rats and in spayed rats injected with either estrogen or progesterone. The technique for preparing and staining the smears (modified Shorr's staining procedure) is outlined. A simplified system of classification which allows the accurate identification of the various stages of the reproductive state in the rat is described. Standing estrus, as well as the influence of estrogen on spayed rats, is characterized by marked cornification of the cells and the disappearance of leukocytes. At the end of estrus, the cornified layer is sloughed off and invasion by leukocytes occurs. During diestrus, as well as in untreated ovariectomized rats, the vaginal contents consistently lack cornified cells whereas leukocytes are very plentiful. Proestrus follows diestrus: the vaginal smear is devoid of leukocytes and characterized by nucleated epithelial cells. Pregnancy, as well as the influence of progesterone on ovariectomized rats, is also characterized by epithelial growth and desquamation but at different rates, resulting in the presence of intermediate cells, and polymorphs and mucus forming a noticeable background to the smear. Since vaginal smears display cell pictures characterist" Braz J Biol. 2002 Nov;62(4A):609-14. Epub 2003 Feb 11. Related Articles, Links
Marcondes FK, Bianchi FJ, Tanno AP. Determination of the estrous cycle phases of rats: some helpful considerations. Braz J Biol. 2002 Nov;62(4A):609-14.
"The short length of the estrous cycle of rats makes them ideal for investigation of changes occurring during the reproductive cycle. The estrous cycle lasts four days and is characterized as: proestrus, estrus, metestrus and diestrus, which may be determined according to the cell types observed in the vaginal smear. Since the collection of vaginal secretion and the use of stained material generally takes some time, the aim of the present work was to provide researchers with some helpful considerations about the determination of the rat estrous cycle phases in a fast and practical way. Vaginal secretion of thirty female rats was collected every morning during a month and unstained native material was observed using the microscope without the aid of the condenser lens. Using the 10 x objective lens, it was easier to analyze the proportion among the three cellular types, which are present in the vaginal smear. Using the 40 x objective lens, it is easier to recognize each one of these cellular types. The collection of vaginal lavage from the animals, the observation of the material, in the microscope, and the determination of the estrous cycle phase of all the thirty female rats took 15-20 minutes. "
Haim S, Shakhar G, Rossene E, Taylor AN, Ben-Eliyahu S. Serum levels of sex hormones and corticosterone throughout 4- and 5-day estrous cycles in Fischer 344 rats and their simulation in ovariectomized females. J Endocrinol Invest. 2003 Oct;26(10):1013-22.
"Among inbred strains of rats, the Fischer 344 (F344) is commonly used in immunological and behavioral studies. However, little is known about patterns of sex hormones and corticosterone (CORT) secretion throughout the estrous cycle in this strain, which is characterized by a marked CORT response to stress and variable length of cycles. In the current study, using radioimmunoassays, we assessed serum levels of progesterone, estradiol, LH, testosterone, prolactin and CORT, at 1-h intervals throughout the estrous cycle in F344 female rats with 4- and 5-day cycles, as well as in males. Vaginal smears were obtained from 268 females for 15 consecutive days to determine individual length of the estrous cycle and the exact estrous phase upon blood withdrawal, which was conducted once in each rat on the 12th day of smearing. The results indicated that both 4- and 5-day cyclers have two distinct and marked surges of progesterone, one on proestrus day and the other on diestrous-1 day. Testosterone levels in 5-day cyclers peaked on diestrus-3, one day earlier than in 4-day cyclers. Daily peak levels of CORT gradually increased from estrus day to proestrous day, whereas daily nadir levels of CORT remained unchanged. To simulate the natural kinetics of specific sex hormones in ovariectomized females, different doses of estradiol, progesterone, testosterone, prolactin or CORT were injected s.c. or i.p., or 90-day sustained release pellets containing different doses of estradiol or progesterone were implanted. The findings indicated dose- and time-dependent effects, suggesting regimens for modeling the estrous cycle or replacement therapy."
Larsen B, Markovetz AJ, Galask RP. Quantitative alterations in the genital microflora of female rats in relation to the estrous cycle. J Infect Dis. 1976 Nov;134(5):486-9.
"The virgin female laboratory rat has been studied as a model of the ecosystem represented by the vaginal mucosa and its bacterial flora. Gram-stained vaginal smears abtained from rats having normal estrous cycles showed cyclic variation in the number of bacteria present. Viable plate counts of material obtained by vaginal lavage demonstrated daily changes in the density of the bacterial population of the vagina in relation to the estrous cycle. Bacterial counts observed during the estrus phase of the cycle in individual rats were 10,000 to 100,000 times greater than viable counts observed during the metestrus or diestrus phases of the cycle. These studies represent the first reported demonstration that physiologic changes occurring during the estrous cycle control the size of the bacterial population of the vagina. "
JA Long and HM Evans, The oestrous cycle in the rat and its associated phenomena. Mem. Univ. Calif. 6:1-148, 1922.
Search PubMed: Search May 2006 "rat estrous cycle" 10,653 reference articles of which 476 were reviews. Search term = rat estrous cycle
Data For Carnegie Stages Comparison Graph (Species/Days) |
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Species |
Stage |
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Days |
20 |
22 |
24 |
28 |
30 |
33 |
36 |
40 |
42 |
44 |
48 |
52 |
54 |
55 |
58 |
|
|
Days |
9 |
9.5 |
10 |
10.5 |
11 |
11.5 |
12 |
12.5 |
13 |
13.5 |
14 |
14.5 |
15 |
15.5 |
16 |
|
|
Rat |
Days |
10.5 |
11 |
11.5 |
12 |
12.5 |
13 |
13.5 |
14 |
14.5 |
15 |
15.5 |
16 |
16.5 |
17 |
17.5 |
References
Human - O'Rahilly, Early human development and the chief source of information on staged human embryos. Eur. J. Obstet. Gynec. Reprod. Biol. 9 p273 (1979)
Mouse - Theiler, The house mouse. Springer-Verlag, NY (1972)
Rat - Witschi, Growth. Altman and Dittmer (ed), Fed. Soc. Exp. Biol., Washington (1962)
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