Rabbit Development

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As an embryological tool, the rabbit (Taxon- Oryctolagus cuniculus) along with human was a species which show birth defects with thalidomide (teratogenic effects not detected with prior testing on other species).

These animals are herbivores with a very high breeding rate and number of offspring produced. Rabbit ovulation is induced by mating allowing an accurate staging of embryonic age and pregnancy.

Rabbit Links: 2009 Student Project | Category:Rabbit | Animal Development
Historic Embryology - Rabbit 
1889 Uterus and Embryo | 1905 Normal Plates | 1905 limb veins | 1908 Pancreas | 1908 Pharyngeal Pouches | 1908 intestinal diverticula | 1909 Lymph glands | 1918 Pituitary | 1929 ovulation | 1931 prochordal plate | 1935 Oocyte | 1935 Somites | 1964 Placentation

Some Recent Findings

  • Tracing the emergence of primordial germ cells from bilaminar disc rabbit embryos and pluripotent stem cells[1] "Rabbit embryos develop as bilaminar discs at gastrulation as in humans and most other mammals, whereas rodents develop as egg cylinders. Primordial germ cells (PGCs) appear to originate during gastrulation according to many systematic studies on mammalian embryos. Here, we show that rabbit PGC (rbPGC) specification occurs at the posterior epiblast at the onset of gastrulation. Using newly derived rabbit pluripotent stem cells, we show robust and rapid induction of rbPGC-like cells in vitro with WNT and BMP morphogens, which reveals SOX17 as the critical regulator of rbPGC fate as in several non-rodent mammals. We posit that development as a bilaminar disc is a crucial determinant of the PGC regulators, regardless of the highly diverse development of extraembryonic tissues, including the amnion. We propose that investigations on rabbits with short gestation, large litters, and where gastrulation precedes implantation can contribute significantly to advances in early mammalian development."
  • Vertebral formula and congenital abnormalities of the vertebral column in rabbits[2] "The aim of this retrospective study of 330 rabbits (164 males, 166 females) was to determine different vertebral formulas and prevalence of congenital vertebral anomalies in rabbits from radiographs of the cervical (C), thoracic (Th), lumbar (L) and sacral (S) segments of the vertebral column. The number of vertebrae in each segment of vertebral column, position of anticlinal vertebra and localisation and type of congenital abnormalities were recorded. In 280/330 rabbits (84.8%) with normal vertebral morphology, seven vertebral formulas were identified: C7/Th12/L7/S4 (252/330, 76.4%), C7/Th12/L6/S4 (11/330, 3.3%), C7/Th13/L7/S4 (8/330, 2.4%), C7/Th12/L7/S5 (4/330, 1.2%), C7/Th12/L8/S4 (3/330, 0.9%), C7/Th12/L7/S6 (1/330, 0.3%) and C7/Th11/L7/S4 (1/330, 0.3%). The anticlinal vertebra was identified as Th10 in 56.4% of rabbits and Th11 in 42.4% of rabbits. Congenital spinal abnormalities were identified in 50/330 (15.2%) rabbits, predominantly as a single pathology (n=44). Transitional vertebrae represented the most common abnormalities (n=41 rabbits) in the thoracolumbar (n=35) and lumbosacral segments (n=6). Five variants of thoracolumbar transitional vertebrae were identified. Cervical butterfly vertebrae were detected in three rabbits. One rabbit exhibited three congenital vertebral anomalies: cervical block vertebra, thoracic hemivertebra and thoracolumbar transitional vertebra. Five rabbits exhibited congenital vertebral abnormalities with concurrent malalignment, specifically cervical kyphosis/short vertebra (n=1), thoracic lordoscoliosis/thoracolumbar transitional vertebrae (n=1), thoracic kyphoscoliosis/wedge vertebrae (n=2) and thoracolumbar lordoscoliosis/thoracolumbar transitional vertebrae/lumbosacral transitional vertebrae (n=1). These findings suggest that vertebral columns in rabbits display a wide range of morphologies, with occasional congenital malformations." axial skeleton

More recent papers  
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Search term: Rabbit Development | Rabbit Embryology | Oryctolagus cuniculus development

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Gonad differentiation in the rabbit: evidence of species-specific features[3] "The rabbit is an attractive species for the study of gonad differentiation because of its 31-day long gestation, the timing of female meiosis around birth and the 15-day delay between gonadal switch and the onset of meiosis in the female. ...Firstly, the peak of SRY gene expression that is observed in early differentiated XY gonads in numerous mammals was also seen in the rabbit, but this expression was maintained at a high level until the end of puberty. Secondly, a peak of aromatase gene expression was observed at two-thirds of the gestation in XX gonads as in many other species except in the mouse. Thirdly, the expression of STRA8 and DMC1 genes (which are known to be specifically expressed in germ cells during meiosis) was enhanced in XX gonads around birth but also slightly and significantly in XY gonads at the same time, even though no meiosis occurs in XY gonad at this stage."
  • Stability of the reproductive variables and fetal malformations from control animals and animals treated with thalidomide in Kbl:JW rabbits over two decades[4] "We retrospectively analyzed the reproductive variables and the spontaneous malformations in the historical control data from the embryo-fetal development studies conducted in our laboratories with Kbl:JW rabbits over two decades (1990-2010) and fetal malformations induced by thalidomide in 1988, 1995 and 2007. ...Therefore, it is concluded that Kbl:JW rabbit is one of the useful rabbit strains to evaluate the effects of test substances on embryo-fetal development, especially in view of the chronological stability of spontaneous or drug-induced malformations in the fetuses." Thalidomide
  • Rabbit whole embryo culture[5] "Although the rabbit is used extensively in developmental toxicity testing, relatively little is known about the fundamental developmental biology of this species let alone mechanisms underlying developmental toxicity. This paucity of information about the rabbit is partly due to the historic lack of whole embryo culture (WEC) methods for the rabbit, which have only been made available fairly recently. ... During this 48 h culture period, major phases of organogenesis can be studied including cardiac looping and segmentation, neural tube closure, and development of anlagen of the otic system, eyes and craniofacial structures, somites and early phases of limb development (up to bud stage), as well as expansion and closure of the visceral yolk sac around the embryo."
  • Ultrasonographic characterisation of prenatal development in European brown hares (Lepus europaeus PALLAS, 1778) [6] "In contrast with the European rabbit, a distant relative, European hares give birth to precocial young. A comparison of the prenatal growth rate of both species suggests that the precocial state of the hare neonate is a more recently derived evolutionary characteristic, whereas the altricial condition of rabbits represents the ancestral mode."
  • Promoter analysis of the rabbit POU5F1 gene and its expression in preimplantation stage embryos [7] "The POU5F1 gene encodes the octamer-binding transcription factor-4 (Oct4). It is crucial in the regulation of pluripotency during embryonic development and widely used as molecular marker of embryonic stem cells (ESCs). ...Notably, we are the first to report that the rabbit POU5F1 is not restricted to ICM cells only, but it is expressed in trophoblast cells as well."


Oryctolagus cuniculus

Taxonomy Id: 9986 Rank: species

Genetic code: Translation table 1 (Standard) Mitochondrial genetic code: Translation table 2 Other names: New Zealand rabbit[includes], rabbits[common name], European rabbit[common name], Japanese white rabbit[common name], domestic rabbit[common name], rabbit[common name], Lepus cuniculus[misnomer]

Lineage( abbreviated ): Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Mammalia; Eutheria; Lagomorpha; Leporidae; Oryctolagus


  • The Oryctolagus cuniculus haploid genome is estimated to be 3500 Mb.
  • The diploid genome is organized in 21 pairs of autosomes and two sex chromosomes.
  • Rabbit gene sequences are more similar to human sequences than rodent ones.
Links: Genome Project Report

Rabbit Reproductive Cycle

  • Rabbits are seasonal breeders with the peak of reproductive activity occurring in the spring and early summer.
  • The female is always in estrus and mating induces ovulation (reflex ovulators).
  • Following mating the ovarian follicles remain active for 12 to 16 days if the doe is not fertilized.
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Developmental Timeline

Early growth of the rabbit morula and blastocyst.[8]

Early development data from an in vitro development study.[9]

Fertilization - penetration of most ova during the first hour after ovulation.
  1. 0-16 h - pronuclei
  2. 16-22 h - 2 cell
  3. 22-29 h - 4 cell
  4. 29-32 h - 8 cell
  5. 32-77h - morula
  6. 77-98h - blastocyst
  7. 98h + - hatching blastocyst
  8. 6 Days - gastrulation starts.
Gastrulation planar cell move icon.jpg
 ‎‎Planar Movement
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Gonad Development

Rabbit gonad timeline.jpg

Timeline of rabbit gonad development.[3]

Day post coïtum (dpc)

  • 9 - first germ cells are detected in both sexes.
  • 14 - gonad macroscopically evident, the mesonephros and gonads are still connected and interactions between tissues are probable.
  • 16 - most germ cells already entered the genital ridges (crests).
  • 16 to 25 - regression of the mesonephros.
  • 23 - gonadal and mesonephric tissues are separated by connective tissue. Thought to prevent the migration of cells and other substances.

Days post partum (dpp)

  • birth - XX gonads first signs of meiosis.
  • 50 - XY gonads first signs of meiosis.
  • 70 - blood-testis barrier is definitively complete.

(text modified from reference[3])

Links: Genital System Development

Historic Images

The following plates are from Normal Plates of the Development of Vertebrates Vol. 5. 1905 Rabbit (Lepus cuniculus) by Charles S. Minot and Edwing Taylor.

Keibel1905 plate01.jpg Keibel1905 plate02.jpg Keibel1905 plate03.jpg

Pincus G. and Enzmann EV. The Comparative Behavior of Mammalian Eggs in Vivo and in Vitro. (1935) J Exp Med. 62(5):665-75. PMID 19870440

The following drawings were compiled in the textbooks: Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co; Foster, M., Balfour, F. M., Sedgwick, A., & Heape, W. (1883). The Elements of Embryology. (2nd ed.). London: Macmillan and Co.

Foster096.jpg Rabbit's ovum between 70-90 hours after impregnation, after E. van Beneden.
Bailey066.jpg Historic drawing of a Transverse sections of embryonic disks of rabbit, (a) Kolliker, (b) Rabl.
a, section through primitive streak of embryo of 6 days and 18 hours; b, section through Hensen's node of embryo of 7 days and 3 hours.
Bailey078.jpg Transverse section through primitive groove of rabbit embryo, van Beneden.
Bailey079.jpg Transverse section through primitive groove of rabbit embryo, van Beneden.
Foster106.jpg Embryo rabbits of about nine days from the dorsal side, Kolliker.
Foster107.jpg Embryo rabbit of about nine days transverse section through the head, Kolliker. B. is a more highly magnified representation of part of A.
Bailey161.jpg Surface view of area vasculosa of a rabbit embryo of 11 days, van Beneden and Julin.
Foster108.jpg Advanced embryo of a rabbit (about twelve days), by Mr Weldon.

Limb Vasculature (veins)
Bailey203.jpg Bailey204.jpg Bailey205.jpg
Rabbit embryo of 14 days (11 mm), modified from Lewis. Rabbit embryo of 14 days and 18 hours (14.5 mm), modified from Lewis. Rabbit embryo of 17 days (21 mm), modified from Lewis.

Rabbit Placentation

Rabbit implantation and placentation is a centric (or fusion) type, where the blastocyst adheres only to the epithelial cells (apical region) by trophectoderm forming projections.[10]

Neural Development

The data below is summarised from an excellent study of early neural development in the rabbit.[11] The same authors have studied neural development in the pig.

  • 6 - 8 somite stage - the flat neural plate transforms into a V-shaped neural groove (beginning at rhombo-cervical level)
  • 8 and 9 somite stage - multiple closure sites occur simultaneously at three levels
  1. incipient pros-mesencephalic transition
  2. incipient mes-rhombencephalic transition
  3. level of the first pairs of somites

results in four transient neuropores

anterior neuropore

  • 9-11 somite stages - anterior and rhombencephalic neuropores close
  • mesencephalic neuropore is very briefly present

posterior neuropore

  • largest and remains open longest
  • 9-10 somite stages - tapered (cranial) portion closes fast within
  • wide (caudal) portion closes up to a narrow slit
  • further closure slows
  • 22 somite stage - full closure occurs

compared with chick and mouse - sequence of multiple site closure resembles that of the mouse embryo, but other important aspects of neurulation resemble those of the chick embryo. In contrast to mouse and chick, no time lag between closure at the three closure sites in the rabbit was seen


Ultrasound day16 rabbit.jpg
 ‎‎Rabbit Embryo
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Ultrasound of a 16 day rabbit embryo.


The rabbit's uterus has six longitudinal folds, symmetrically disposed ; the line of insertion of the mesentery (mesometrium or broad ligament) corresponds to the space between two folds, which alone participate in the formation of the placenta; accordingly we may designate them as the placental folds.[12]

Rabbit Immune Development

Rabbits generate their antibody repertoire in three stages.[13]

  1. Neonatal repertoire is generated by B lymphopoiesis in fetal liver and bone marrow (limited by preferential V(H) gene segment usage).
  2. Between 4 and 8 weeks after birth gut-associated lymphoid tissue (GALT) a complex primary antibody repertoire.
  3. The primary antibody repertoire is subsequently modified during antigen-dependent immune responses (the secondary repertoire).

Rabbits uniquely develop a primary antibody repertoire through somatic diversification of Ig genes (dependent on intestinal microbial flora).

The esacculus rotundus is located at the ileocaecal junction as an enlargement of the large intestine and contains lymphoid tissue.

Postnatal Rabbit Growth

Postnatal growth data from 2 to 34 weeks of age at biweekly intervals for New Zealand white rabbit.[14]

  • 17 male and 12 female rabbits, with the data tabulated separately.
  • Skeletal growth was complete at 28 weeks, with the 34 week values mature adult lengths.

Mean body weight

  • 2 weeks of age was 6% that at 34 weeks
  • 16 weeks was 72% of the weight at 34 weeks
  • weight continued to increase in the adult.

Mean body length

  • 2 weeks was 40% that at 34 weeks
  • 16 weeks was 91% of mature adult

Mean femoral length

  • 2 weeks was 38% of adult
  • 16 weeks was 95% of adult

Mean tibial length

  • 2 weeks was 38% of adult
  • 16 weeks was 94% of adult


  1. Kobayashi T, Castillo-Venzor A, Penfold CA, Morgan M, Mizuno N, Tang WWC, Osada Y, Hirao M, Yoshida F, Sato H, Nakauchi H, Hirabayashi M & Surani MA. (2021). Tracing the emergence of primordial germ cells from bilaminar disc rabbit embryos and pluripotent stem cells. Cell Rep , 37, 109812. PMID: 34644585 DOI.
  2. Proks P, Stehlik L, Nyvltova I, Necas A, Vignoli M & Jekl V. (2018). Vertebral formula and congenital abnormalities of the vertebral column in rabbits. Vet. J. , 236, 80-88. PMID: 29871755 DOI.
  3. 3.0 3.1 3.2 Daniel-Carlier N, Harscoët E, Thépot D, Auguste A, Pailhoux E & Jolivet G. (2013). Gonad differentiation in the rabbit: evidence of species-specific features. PLoS ONE , 8, e60451. PMID: 23593221 DOI.
  4. Kawamura Y, Matsumoto K & Sato K. (2012). Stability of the reproductive variables and fetal malformations from control animals and animals treated with thalidomide in Kbl:JW rabbits over two decades. Congenit Anom (Kyoto) , 52, 191-202. PMID: 23181494 DOI.
  5. Marshall VA & Carney EW. (2012). Rabbit whole embryo culture. Methods Mol. Biol. , 889, 239-52. PMID: 22669668 DOI.
  6. Roellig K, Goeritz F & Hildebrandt TB. (2010). Ultrasonographic characterisation of prenatal development in European brown hares (Lepus europaeus PALLAS, 1778): an evolutionary approach. Reprod. Fertil. Dev. , 22, 448-58. PMID: 20047730 DOI.
  7. Kobolak J, Kiss K, Polgar Z, Mamo S, Rogel-Gaillard C, Tancos Z, Bock I, Baji AG, Tar K, Pirity MK & Dinnyes A. (2009). Promoter analysis of the rabbit POU5F1 gene and its expression in preimplantation stage embryos. BMC Mol. Biol. , 10, 88. PMID: 19732419 DOI.
  8. Warner SM, Conlon FV & Kane MT. (2003). Inositol transport in preimplantation rabbit embryos: effects of embryo stage, sodium, osmolality and metabolic inhibitors. Reproduction , 125, 479-93. PMID: 12683919
  9. Sultana F, Hatori M, Shimozawa N, Ebisawa T & Sankai T. (2009). Continuous observation of rabbit preimplantation embryos in vitro by using a culture device connected to a microscope. J. Am. Assoc. Lab. Anim. Sci. , 48, 52-6. PMID: 19245751
  10. Lee KY & DeMayo FJ. (2004). Animal models of implantation. Reproduction , 128, 679-95. PMID: 15579585 DOI.
  11. Peeters MC, Viebahn C, Hekking JW & van Straaten HW. (1998). Neurulation in the rabbit embryo. Anat. Embryol. , 197, 167-75. PMID: 9543335
  12. Minot CS. Uterus And Embryo - I. Rabbit II. Man. (1889) J Morphol. 2:
  13. Lanning D, Zhu X, Zhai SK & Knight KL. (2000). Development of the antibody repertoire in rabbit: gut-associated lymphoid tissue, microbes, and selection. Immunol. Rev. , 175, 214-28. PMID: 10933605
  14. Masoud I, Shapiro F, Kent R & Moses A. (1986). A longitudinal study of the growth of the New Zealand white rabbit: cumulative and biweekly incremental growth rates for body length, body weight, femoral length, and tibial length. J. Orthop. Res. , 4, 221-31. PMID: 3712130 DOI.


Fischer B, Chavatte-Palmer P, Viebahn C, Navarrete Santos A & Duranthon V. (2012). Rabbit as a reproductive model for human health. Reproduction , 144, 1-10. PMID: 22580370 DOI.

Püschel B, Bitzer E, Blum M & Viebahn C. (2010). Mounting, embedding, and sectioning of early rabbit embryos. Cold Spring Harb Protoc , 2010, pdb.prot5356. PMID: 20150115 DOI.

Püschel B, Daniel N, Bitzer E, Blum M, Renard JP & Viebahn C. (2010). The rabbit (Oryctolagus cuniculus): a model for mammalian reproduction and early embryology. Cold Spring Harb Protoc , 2010, pdb.emo139. PMID: 20150104 DOI.


Hassoun R, Schwartz P, Rath D, Viebahn C & Männer J. (2010). Germ layer differentiation during early hindgut and cloaca formation in rabbit and pig embryos. J. Anat. , 217, 665-78. PMID: 20874819 DOI.

Idkowiak J, Weisheit G & Viebahn C. (2004). Polarity in the rabbit embryo. Semin. Cell Dev. Biol. , 15, 607-17. PMID: 15271306 DOI.

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Cite this page: Hill, M.A. (2024, June 12) Embryology Rabbit Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Rabbit_Development

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