Mouse Estrous Cycle
|Embryology - 24 Nov 2017 Expand to Translate|
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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.
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Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Xinye Wang, Priya Mittal, Carlos A Castro, Gabriel Rajkovic, Aleksandar Rajkovic Med12 regulates ovarian steroidogenesis, uterine development and maternal effects in the mammalian egg. Biol. Reprod.: 2017; PubMed 29126187
Cristina Bichels Hebeda, Isabel Daufenback Machado, Isadora Reif-Silva, Jusciele Brogin Moreli, Sonia Maria Oliani, Suchita Nadkarni, Mauro Perretti, Estela Bevilacqua, Sandra H P Farsky Endogenous annexin A1 (AnxA1) modulates early phase gestation and offspring sex-ratio skewing. J. Cell. Physiol.: 2017; PubMed 29115663
Natalie M Hohos, Kirstin J Cho, Delaney C Swindle, Malgorzata E Skaznik-Wikiel High-fat diet exposure, regardless of induction of obesity, is associated with altered expression of genes critical to normal ovulatory function. Mol. Cell. Endocrinol.: 2017; PubMed 29097167
Kelsi N Dodds, Elizabeth A H Beckett, Susan F Evans, Mark R Hutchinson Lesion development is modulated by the natural estrous cycle and mouse strain in a minimally-invasive model of endometriosis. Biol. Reprod.: 2017; PubMed 29069288
Daniëlle Peterse, M Mercedes Binda, Dorien F O, Arne Vanhie, Amelie Fassbender, Joris Vriens, Thomas M D'Hooghe Of Mice and Women: a Laparoscopic Mouse Model for Endometriosis. J Minim Invasive Gynecol: 2017; PubMed 29032250
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
Image Source: High-resolution ultrasound biomicroscopy for monitoring ovarian structures in mice. 
For more detailed histological information see [#Champlin Champlin etal., 1973].
Uterus The changes in the uterus may not be particularly well-marked.
- Histological changes in the luminal epithelium
- Histological changes in the glandular epithelium
- Secretory activity of uterine glands
- Changes in stromal cells, e.g. number of leucocytes
- Overall changes in the size distention and shape of the lumen.
Vagina Note the changes in the vaginal epithelium.
- The number of mitotic figures
- The number of layers in the epithelium
- The amount of cornification, and the changes from live to dead cells.
- Surface mucus coating the epithelium
- Presence or absence of infiltrating polymorphonuclear leucocytes.
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 Stage Species Comparison
- Mouse Stages: E1 | E2.5 | E3 | E3.5 | E4.5 | E5.0 | E6.0 | E7.0 | E7.5 | E8.0 | E8.5 | E9.0 | E9.5 | E10 | E10.5 | E11 | E11.5 | E12 | E12.5 | E13 | E13.5 | E14 | E14.5 | E15 | E15.5 | E16 | E16.5 | E17 | E17.5 | E18 | E18.5 | E19 | E20 | Timeline | About timed pregnancy
|Note these Carnegie stages are only approximate day timings for average of embryos. Links: Carnegie Stage Comparison
- Shannon L Byers, Michael V Wiles, Sadie L Dunn, Robert A Taft Mouse estrous cycle identification tool and images. PLoS ONE: 2012, 7(4);e35538 PubMed 22514749 | [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0035538 PLoS One.
- 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
- Claudia S Caligioni Assessing reproductive status/stages in mice. Curr Protoc Neurosci: 2009, Appendix 4;Appendix 4I PubMed 19575469
- 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
- Anne Bachelot, Nadine Binart Corpus luteum development: lessons from genetic models in mice. Curr. Top. Dev. Biol.: 2005, 68;49-84 PubMed 16124996
- Kaushik Deb, Jeff Reese, Bibhash C Paria Methodologies to study implantation in mice. Methods Mol. Med.: 2006, 121;9-34 PubMed 16251731
- 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
Michelle C Cora, Linda Kooistra, Greg Travlos Vaginal Cytology of the Laboratory Rat and Mouse: Review and Criteria for the Staging of the Estrous Cycle Using Stained Vaginal Smears. Toxicol Pathol: 2015; PubMed 25739587
Charles L Chaffin, Catherine A Vandevoort Follicle growth, ovulation, and luteal formation in primates and rodents: a comparative perspective. Exp. Biol. Med. (Maywood): 2013, 238(5);539-48 PubMed 23856905
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
- 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. 2017 Embryology Mouse Estrous Cycle. Retrieved November 24, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Estrous_Cycle