Mouse Estrous Cycle

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Introduction

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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.

Note "estrus" the alternate English spelling "oestrus".


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Some Recent Findings

Mouse estrous cycle stage identification
Mouse estrous cycle stage identification[1]
  • Mouse estrous cycle identification tool and images[1] "The efficiency of producing timed pregnant or pseudopregnant mice can be increased by identifying those in proestrus or estrus....Presented here are a series of images of the vaginal opening at each stage of the estrous cycle for 3 mouse strains of different coat colors: black (C57BL/6J), agouti (CByB6F1/J) and albino (BALB/cByJ). When all 4 stages (proestrus, estrus, metestrus, and diestrus) need to be identified, vaginal cytology is regarded as the most accurate method. An identification tool is presented to aid the user in determining the stage of estrous when using vaginal cytology. These images and descriptions are an excellent resource for learning how to determine the stage of the estrous cycle by visual observation or vaginal cytology."
  • Refining timed pregnancies in two strains of genetically engineered mice.[2] "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.[3]
  • Uterine NK cells in murine pregnancy.[4] "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.[5] "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.[6] "....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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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

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.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Mouse Estrous Cycle

Jessica G Wallace, Ryan H Potts, Jake C Szamosi, Michael G Surette, Deborah M Sloboda The murine female intestinal microbiota does not shift throughout the estrous cycle. PLoS ONE: 2018, 13(7);e0200729 PubMed 30011327

Flávia Werner da Rocha Jesuíno, Jaqueline Pavesi Reis, Juliana Cristina Pereira Whitaker, Adriana Campos, Maria Verônica Dávila Pastor, Valdir Cechinel Filho, Nara Lins Meira Quintão Effect of Synadenium grantii and its isolated compound on dysmenorrhea behavior model in mice. Inflammopharmacology: 2018; PubMed 29948493

Jisoo Han, Wooyoung Jeong, Min Jeong Gu, Inkyu Yoo, Cheol-Heui Yun, Jinyoung Kim, Hakhyun Ka Cysteine-X-Cysteine Motif Chemokine Ligand 12 and Its Receptor CXCR4: Expression, Regulation, and Possible Function at the Maternal-Conceptus Interface during Early Pregnancy in Pigs. Biol. Reprod.: 2018; PubMed 29945222

Carrie D Fischer, Garrett L Wachoski-Dark, Danielle M Grant, Sarah A Bramer, Claudia Klein Interferon epsilon is constitutively expressed in equine endometrium and up-regulated during the luteal phase. Anim. Reprod. Sci.: 2018; PubMed 29807828

Mouse Estrous Cycle

Mouse Estrous Cycle
Stage
Ovary
Uterus
Vagina
Smear
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 Estrous Cycle

Mouse Ovarian Follicle Size

Mouse ovarian follicle size.jpg

Image Source: High-resolution ultrasound biomicroscopy for monitoring ovarian structures in mice.[7]

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 Stage Species Comparison

Mouse Stages: E1 | E2.5 | E3.0 | 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 | E18.5 | E18 | E18.5 | E19 | E20 | Timeline | About timed pregnancy


Species Embryonic Comparison Timeline
Carnegie Stage
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Human Days 1 2-3 4-5 5-6 7-12 13-15 15-17 17-19 20 22 24 28 30 33 36 40 42 44 48 52 54 55 58
Mouse Days 1 2 3 E4.5 E5.0 E6.0 E7.0 E8.0 E9.0 E9.5 E10 E10.5 E11 E11.5 E12 E12.5 E13 E13.5 E14 E14.5 E15 E15.5 E16
Rat Days 1 3.5 4-5 5 6 7.5 8.5 9 10.5 11 11.5 12 12.5 13 13.5 14 14.5 15 15.5 16 16.5 17 17.5
Note these Carnegie stages are only approximate day timings for average of embryos. Links: Carnegie Stage Comparison
Table References  
Human

O'Rahilly R. (1979). Early human development and the chief sources of information on staged human embryos. Eur. J. Obstet. Gynecol. Reprod. Biol. , 9, 273-80. PMID: 400868

Mouse
Theiler K. The House Mouse: Atlas of Mouse Development (1972, 1989) Springer-Verlag, NY. Online
OTIS EM & BRENT R. (1954). Equivalent ages in mouse and human embryos. Anat. Rec. , 120, 33-63. PMID: 13207763

Rat
Witschi E. Rat Development. In: Growth Including Reproduction and Morphological Development. (1962) Altman PL. and Dittmer DS. ed. Fed. Am. Soc. Exp. Biol., Washington DC, pp. 304-314.
Pérez-Cano FJ, Franch À, Castellote C & Castell M. (2012). The suckling rat as a model for immunonutrition studies in early life. Clin. Dev. Immunol. , 2012, 537310. PMID: 22899949 DOI.

Timeline Links: human timeline | mouse timeline | mouse detailed timeline | chicken timeline | rat timeline | Medaka | Category:Timeline

References

  1. 1.0 1.1 Byers SL, Wiles MV, Dunn SL & Taft RA. (2012). Mouse estrous cycle identification tool and images. PLoS ONE , 7, e35538. PMID: 22514749 DOI.
  2. Mader SL, Libal NL, Pritchett-Corning K, Yang R & Murphy SJ. (2009). Refining timed pregnancies in two strains of genetically engineered mice. Lab Anim (NY) , 38, 305-10. PMID: 19701181 DOI.
  3. Caligioni CS. (2009). Assessing reproductive status/stages in mice. Curr Protoc Neurosci , Appendix 4, Appendix 4I. PMID: 19575469 DOI.
  4. Bilinski MJ, Thorne JG, Oh MJ, Leonard S, Murrant C, Tayade C & Croy BA. (2008). Uterine NK cells in murine pregnancy. Reprod. Biomed. Online , 16, 218-26. PMID: 18284876
  5. Bachelot A & Binart N. (2005). Corpus luteum development: lessons from genetic models in mice. Curr. Top. Dev. Biol. , 68, 49-84. PMID: 16124996 DOI.
  6. Deb K, Reese J & Paria BC. (2006). Methodologies to study implantation in mice. Methods Mol. Med. , 121, 9-34. PMID: 16251731
  7. Jaiswal RS, Singh J & Adams GP. (2009). High-resolution ultrasound biomicroscopy for monitoring ovarian structures in mice. Reprod. Biol. Endocrinol. , 7, 69. PMID: 19580664 DOI.


Reviews

Cora MC, Kooistra L & Travlos G. (2015). Vaginal Cytology of the Laboratory Rat and Mouse: Review and Criteria for the Staging of the Estrous Cycle Using Stained Vaginal Smears. Toxicol Pathol , 43, 776-93. PMID: 25739587 DOI.

Chaffin CL & Vandevoort CA. (2013). Follicle growth, ovulation, and luteal formation in primates and rodents: a comparative perspective. Exp. Biol. Med. (Maywood) , 238, 539-48. PMID: 23856905 DOI.

Articles

Yang YJ, Cao YJ, Bo SM, Peng S, Liu WM & Duan EK. (2006). Leptin-directed embryo implantation: leptin regulates adhesion and outgrowth of mouse blastocysts and receptivity of endometrial epithelial cells. Anim. Reprod. Sci. , 92, 155-67. PMID: 16023802 DOI.

Deb K, Reese J & Paria BC. (2006). Methodologies to study implantation in mice. Methods Mol. Med. , 121, 9-34. PMID: 16251731

Lee DS, Yanagimoto Ueta Y, Xuan X, Igarashi I, Fujisaki K, Sugimoto C, Toyoda Y & Suzuki H. (2005). Expression patterns of the implantation-associated genes in the uterus during the estrous cycle in mice. J. Reprod. Dev. , 51, 787-98. PMID: 16210782

Su P, Wu JC, Sommer JR, Gore AJ, Petters RM & Miller WL. (2005). Conditional induction of ovulation in mice. Biol. Reprod. , 73, 681-7. PMID: 15917351 DOI.

Champlin AK, Dorr DL & Gates AH. (1973). Determining the stage of the estrous cycle in the mouse by the appearance of the vagina. Biol. Reprod. , 8, 491-4. PMID: 4736343

Search PubMed

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

Terms

  • 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. (2018, July 18) Embryology Mouse Estrous Cycle. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Mouse_Estrous_Cycle

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