Mouse Estrous Cycle

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Reproductive processes in female mammals are characterised by cyclic alterations in the female tract and in sexual receptivity. The recurrent period of receptivity, or "heat" is called Estrus. The estrous cycle has been most extensively studied in laboratory rodents (mice and rats). Rats kept separate from males in the laboratory repeat the Estrous cycle throughout the year at intervals of about five days, unless subjected to pregnancy, pseudo-pregnancy (after a sterile mating), or disease. The cycle involves the whole of the reproductive tract, and it is possible to determine the sexual status of the female rat by examination of smears prepared from the vaginal fluid.

Rats and mice are examples of polyestrus mammals (as are cats which are seasonally polyoestrus). Monestrus forms (most wild animals - foxes, bears, wolves etc.) complete a single estrous cycle annually. In the wild, rats and mice probably suspend the cycle for a period during the winter; the reproductive organs are in a state of quiescence, called anestrus.

Mouse Links: Introduction | Mouse Stages | Mouse Timeline | Mouse Timeline Detailed | Mouse Estrous Cycle | Mouse Knockout | Movie - Cephalic Plexus | ANAT2341 Project (2009) | Category:Mouse

Some Recent Findings

  • Refining timed pregnancies in two strains of genetically engineered mice. [1]"In both sEHKO and GFP colonies, increases in body weight at 1 and 2 weeks after timed male exposure more reliably and consistently indicated pregnancy than did plug detection."
  • Assessing reproductive status/stages in mice. [2]
  • Uterine NK cells in murine pregnancy. [3]"Murine uterine natural killer (uNK) cells are transient, short-lived, terminally differentiated lymphocytes found in decidualized endometrium. ....Activated uNK cells are now considered critical for appropriate endometrial angiogenesis in early implantation site development and in non-gestational endometrium."
  • Corpus luteum development: lessons from genetic models in mice.[4] "The life span and function of the corpus luteum is regulated by complex interactions between stimulatory (luteotrophic) and inhibitory (luteolytic) mediators. ... In rodents, prolactin is the major luteotrophic hormone by maintaining the structural and functional integrity of the corpus luteum for several days after mating. Other factors involved in steroidogenesis, control of cell cycle, apoptosis, and tissue remodeling have been shown to play a role in corpus luteum development and maintenance. Especially, PGF2alpha seems to be the most potent luteolytic hormone."
  • Methodologies to study implantation in mice.[5] "....The process of implantation can be postponed and reinstated experimentally by manipulating ovarian estrogen secretion. Stromal decidualization can also be induced experimentally in the hormonally prepared uterus in response to stimuli other than the embryo. ...This chapter describes the routine laboratory methodologies to study the events of early pregnancy, with special emphasis on the implantation process in mice."
More recent papers
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Search term: Mouse Estrous Cycle

Tandra R Chakraborty, Laxminarasimha Donthireddy, Debasis Adhikary, Sanjoy Chakraborty Long-Term High Fat Diet Has a Profound Effect on Body Weight, Hormone Levels, and Estrous Cycle in Mice. Med. Sci. Monit.: 2016, 22;1601-1608 PubMed 27171231

Yali Yang, Lirong Ren, Lifeng Sun, Chen Huang, Tianxia Xiao, Baobei Wang, Jie Chen, Brian A Zabel, Peigen Ren, Jian V Zhang The role of GPR1 signaling in mice corpus luteum. J. Endocrinol.: 2016; PubMed 27149986

Kaiyu Kubota, Wei Cui, Pramod Dhakal, Michael W Wolfe, M A Karim Rumi, Jay L Vivian, Katherine F Roby, Michael J Soares Rethinking progesterone regulation of female reproductive cyclicity. Proc. Natl. Acad. Sci. U.S.A.: 2016; PubMed 27035990

Y Zeng, H Sun, Y Li, M Shao, P Han, X Yu, L He, Y Xu, S Li Exposure to triptolide affects follicle development in NIH mice: Role of endoplasmic reticulum stress in granulosa cell apoptosis. Hum Exp Toxicol: 2016; PubMed 27022166

E Studer, J Näslund, A Westman, A Carlsson, E Eriksson The effects of the dopamine stabilizer (-)-OSU6162 on aggressive and sexual behavior in rodents. Transl Psychiatry: 2016, 6;e762 PubMed 27003188

Mouse Estrous Cycle

Diestrus Small follicles only are present with large corpora lutea from the previous ovulation. These secrete for only a very short time unless pregnancy or pseudopregnancy intervene. Small and anaemic, low motility, lumen small and slit-like. Cells of the uterine mucosa columnar; polymorphonuclear leucocytes in stroma; endometrial glands collapsed, atrophic. Epithelium thin, mitotic figures infrequent. Leucocytes abundant in stroma, migrate through the epithelium into vaginal lumen. Stringy mucous in which are entangled many leucocytes and a few nucleated epithelial cells.
Proestrus Some follicles grow rapidly. Become more vascular, water content increases, organ distends. Contractility more pronounced. Epithelial cells become higher (continuing into estrus). Leucocytes disappear from mucosa. Endometrial glands hypertrophy. Epithelum thickens, numerous mitoses in inner layers. Old layers of epithelium line the lumen. Leucocytes no longer migrate through the epithelium. Superficial epithelial cells slough off into lumen. Largely small, round, nucleated epithelial cells, singly or in sheets. None to few leucoytes.
Estrus Ovulation in the rat is spontaneous and occurs about 10 hours after the beginning of estrus. "Heat" (receptivity) lasts about 13 hours. Usually 10-20 eggs ovulated each time. gains maximum vascularisation. Epithelial cells reach maximum development. No leucocytes. Outer layer of epithelial cells become cornified and sloughed into the lumen. In early estrus these cells retain their nuclei, but in later stages no nuclei visible and the cells are irregular, flat, cornified plates. The skin around the vaginal orifice becomes swollen. Contains hundreds of large cornified cells (squames) with degenerate nuclei. Towards the end of estrus the smear becomes "cheesy" - masses of adherent cornified cells.
Metestrus Many corpora lutea, which secrete only for a very short time, and small follicles. Epithelium continues vacuolar degeneration and replacement. Leucocytes in stroma. Decrease in size and vascularity. Deeper layers of the estrous epithelium now line the lumen, the older, superficial layers having become cornified and sloughed off. Reduction of mitotic activity in epithelium. Leucocytes in stroma and migrating through the epithelium into the lumen. Many leucocytes and a few cornified cells.

Mouse Ovarian Follicle Size

Mouse ovarian follicle size.jpg

Image Source: High-resolution ultrasound biomicroscopy for monitoring ovarian structures in mice. [6]

Histological Features

For more detailed histological information see [#Champlin Champlin etal., 1973].

Uterus The changes in the uterus may not be particularly well-marked.

  1. Histological changes in the luminal epithelium
  2. Histological changes in the glandular epithelium
  3. Secretory activity of uterine glands
  4. Changes in stromal cells, e.g. number of leucocytes
  5. Overall changes in the size distention and shape of the lumen.

Vagina Note the changes in the vaginal epithelium.

  1. The number of mitotic figures
  2. The number of layers in the epithelium
  3. The amount of cornification, and the changes from live to dead cells.
  4. Surface mucus coating the epithelium
  5. Presence or absence of infiltrating polymorphonuclear leucocytes.

Vaginal Smears

Relate the appearance of the smears to the sections of the vagina, noting particularly the composition of cells in the smear and the vaginal epithelium.

1. Relative numbers and appearance of cell types - epithelial and polymorphs.

2. Presence of mucus.

Carnegie Stages Comparison

Data For Carnegie Stages Comparison Graph (Species/Days)
[cstages.htm (All Species Data)]
Species Stage
Human Days 20 22 24 28 30 33 36 40 42 44 48 52 54 55 58
Mouse 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

Table 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)


  1. Sarah L Mader, Nicole L Libal, Kathleen Pritchett-Corning, Rui Yang, Stephanie J Murphy Refining timed pregnancies in two strains of genetically engineered mice. Lab Anim (NY): 2009, 38(9);305-10 PubMed 19701181
  2. Claudia S Caligioni Assessing reproductive status/stages in mice. Curr Protoc Neurosci: 2009, Appendix 4;Appendix 4I PubMed 19575469
  3. M J Bilinski, J G Thorne, M J Oh, S Leonard, C Murrant, C Tayade, B A Croy Uterine NK cells in murine pregnancy. Reprod. Biomed. Online: 2008, 16(2);218-26 PubMed 18284876
  4. Anne Bachelot, Nadine Binart Corpus luteum development: lessons from genetic models in mice. Curr. Top. Dev. Biol.: 2005, 68;49-84 PubMed 16124996
  5. Kaushik Deb, Jeff Reese, Bibhash C Paria Methodologies to study implantation in mice. Methods Mol. Med.: 2006, 121;9-34 PubMed 16251731
  6. Rajesh S Jaiswal, Jaswant Singh, Gregg P Adams High-resolution ultrasound biomicroscopy for monitoring ovarian structures in mice. Reprod. Biol. Endocrinol.: 2009, 7;69 PubMed 19580664 | PMC2714516



Yong-Jun Yang, Yu-Jing Cao, Shu-Min Bo, Sha Peng, Wei-Min Liu, En-Kui Duan Leptin-directed embryo implantation: leptin regulates adhesion and outgrowth of mouse blastocysts and receptivity of endometrial epithelial cells. Anim. Reprod. Sci.: 2006, 92(1-2);155-67 PubMed 16023802

Kaushik Deb, Jeff Reese, Bibhash C Paria Methodologies to study implantation in mice. Methods Mol. Med.: 2006, 121;9-34 PubMed 16251731

Dong-Soo Lee, Yoshiko Yanagimoto Ueta, Xuenan Xuan, Ikuo Igarashi, Kozo Fujisaki, Chihiro Sugimoto, Yutaka Toyoda, Hiroshi Suzuki Expression patterns of the implantation-associated genes in the uterus during the estrous cycle in mice. J. Reprod. Dev.: 2005, 51(6);787-98 PubMed 16210782

Pei Su, Joyce C Wu, Jeffrey R Sommer, A Jesse Gore, Robert M Petters, William L Miller Conditional induction of ovulation in mice. Biol. Reprod.: 2005, 73(4);681-7 PubMed 15917351

A K Champlin, D L Dorr, A H Gates Determining the stage of the estrous cycle in the mouse by the appearance of the vagina. Biol. Reprod.: 1973, 8(4);491-4 PubMed 4736343

Search PubMed

Search Nov 2009 "estrous cycle" 55440 reference articles of which 4042 were reviews.

Search PubMed: mouse estrous cycle | estrous cycle | mouse anestrus | oestrous cycle


  • a disintegrin and metalloproteinase - (ADAM) a large family (-8, -9, -10, -12, -15 and -17) of secreted proteins suggested to be involved in remodelling mouse uterine tissue during the oestrous cycle.
  • anestrus - lack of a normal estrus cycle.
  • Bruce Effect - pheromones from a strange male can prevent embryo implantation in recently bred female.
  • calling behaviour - vocalization, vocal communication sounds associated with reproductive behaviour in several species.
  • Lee-Boot Effect - female mice housed together (in groups) results in a synchronization of their estrus cycles. In addition, the extended absence of male pheromones leads to a state of anestrus (lack of a normal estrus cycle).
  • major urinary proteins - (MUPs) proteins which carry volatile substances, including pheromones, and protect them during their internal passage (liver to kidneys into urine).
  • pheromone - a secreted chemical in sweat or urine that causes specific physiological responses.
  • Whitten Effect - female mice either singly or housed together (in groups) can be induced into estrus by exposure to male mouse urine or their dirty bedding. The estrous cycle is applicable to many different species, not just the mouse reproductive cycle.

Spelling Note: When searching both American (estrous) and British (oestrous) spellings are used in the literature (More? American and British Spelling Variations). My thanks also to Prof Jill Becker for correcting an obvious spelling error on this page "The adjective is spelled with a 'u' after the o. 'Estrus' refers to the stage of the cycle and is the noun form of the word."

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Cite this page: Hill, M.A. (2016) Embryology Mouse Estrous Cycle. Retrieved May 25, 2016, from

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