Talk:Rabbit Development

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Cite this page: Hill, M.A. (2024, April 14) Embryology Rabbit Development. Retrieved from


Tracing the emergence of primordial germ cells from bilaminar disc rabbit embryos and pluripotent stem cells 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.

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.


Paradis FH, Downey AM, Beaudry F, Pinêtre C, Ellemann-Laursen S, Makin A, Hill K, Singh P, Hargitai J, Forster R, Tavcar R & Authier S. (2019). Interspecies Comparison of Control Data From Embryo-Fetal Development Studies in Sprague-Dawley Rats, New Zealand White Rabbits, and Göttingen Minipigs. Int. J. Toxicol. , 38, 476-486. PMID: 31470750 DOI.

Interspecies Comparison of Control Data From Embryo-Fetal Development Studies in Sprague-Dawley Rats, New Zealand White Rabbits, and Göttingen Minipigs.

Abstract Species-dependent differences in relative incidence of spontaneous variations and malformations should be considered in the assessment of the translational value of reproductive and developmental safety assessments. The objective of this evaluation was to compare litter parameters and the frequency of external, visceral, and skeletal malformations and variations across species in the Sprague-Dawley rat, New Zealand White rabbit, and Göttingen minipig and to determine whether notable differences exist. Pregnant female rats (n = 824), rabbits (n = 540), and minipigs (n = 70) from vehicle control groups were included in the analysis, equating to 10,749 rat, 5,073 rabbit, and 378 pig fetuses collected at term by cesarean delivery. Preimplantation loss was more frequent than postimplantation loss in the rat and rabbit, whereas the opposite was observed in the minipig. Several external and visceral malformations and variations such as domed head, bent tail, abdominal edema, and anal atresia were observed in all 3 species. Visceral malformations of the heart and major blood vessels were remarkably more frequent in the minipig and rabbit, respectively; ventricular and atrium septum defects were observed in 1.9% and 2.1%, respectively, for the minipig fetuses, whereas they were observed in equal or less than 0.02% among the rat and rabbit fetuses evaluated in this study. Understanding species-dependent differences in spontaneous variations and malformations can be useful for the interpretation of embryo-fetal development study results. The current analysis identified relevant differences between commonly used species in reproductive toxicology with potential implications for data assessment. KEYWORDS: Göttingen minipig; New Zealand White rabbit; Sprague-Dawley rat; embryo–fetal toxicology; interspecies PMID: 31470750


Vertebral formula and congenital abnormalities of the vertebral column in rabbits

Vet J. 2018 Jun;236:80-88. doi: 10.1016/j.tvjl.2018.04.016. Epub 2018 Apr 26.

Proks P1, Stehlik L2, Nyvltova I2, Necas A2, Vignoli M3, Jekl V4. Author information 1 Small Animal Clinic, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences Brno, Czech Republic; Central European Institute of Technology (CEITEC), Brno, Czech Republic. Electronic address: 2 Small Animal Clinic, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences Brno, Czech Republic. 3 Faculty of Veterinary Medicine, University of Teramo, Piano D́Accio, 641 00, Teramo, Italy. 4 Avian and Exotic Animal Clinics, Faculty of Veterinary Medicine, University of Veterinary and Pharmaceutical Sciences Brno, Czech Republic. Abstract 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. Copyright © 2018 Elsevier Ltd. All rights reserved. KEYWORDS: Congenital anomaly; Rabbit; Radiography; Spine; Transitional vertebra PMID: 29871755 DOI: 10.1016/j.tvjl.2018.04.016


Rho kinase activity controls directional cell movements during primitive streak formation in the rabbit embryo

Development. 2015 Jan 1;142(1):92-8. doi: 10.1242/dev.111583.

Stankova V1, Tsikolia N1, Viebahn C2.


During animal gastrulation, the specification of the embryonic axes is accompanied by epithelio-mesenchymal transition (EMT), the first major change in cell shape after fertilization. EMT takes place in disparate topographical arrangements, such as the circular blastopore of amphibians, the straight primitive streak of birds and mammals or in intermediate gastrulation forms of other amniotes such as reptiles. Planar cell movements are prime candidates to arrange specific modes of gastrulation but there is no consensus view on their role in different vertebrate classes. Here, we test the impact of interfering with Rho kinase-mediated cell movements on gastrulation topography in blastocysts of the rabbit, which has a flat embryonic disc typical for most mammals. Time-lapse video microscopy, electron microscopy, gene expression and morphometric analyses of the effect of inhibiting ROCK activity showed - besides normal specification of the organizer region - a dose-dependent disruption of primitive streak formation; this disruption resulted in circular, arc-shaped or intermediate forms, reminiscent of those found in amphibians, fishes and reptiles. Our results reveal a crucial role of ROCK-controlled directional cell movements during rabbit primitive streak formation and highlight the possibility that temporal and spatial modulation of cell movements were instrumental for the evolution of gastrulation forms. © 2015. Published by The Company of Biologists Ltd. KEYWORDS: Amniote evolution; Cell migration; Mammalian gastrulation; Mesoderm formation; Planar cell polarity; Primitive streak

PMID 25516971


Gonad differentiation in the rabbit: evidence of species-specific features

PLoS One. 2013 Apr 8;8(4):e60451. doi: 10.1371/journal.pone.0060451. Print 2013.

Daniel-Carlier N, Harscoët E, Thépot D, Auguste A, Pailhoux E, Jolivet G. Source UMR 1198, Biologie du Développement et Reproduction, Institut National de la Recherche Agronomique, Jouy en Josas, France.


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. The expression of a series of genes was thus determined by qPCR during foetal life until adulthood, completed by a histological analysis and whenever possible by an immunohistological one. Interesting gene expression profiles were recorded. 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. This was probably a consequence of the synchronous strong NANOS2 gene expression in XY gonad. In conclusion, our data highlighted some rabbit-specific findings with respect to the gonad differentiation process.

PMID 23593221


Rabbit as a reproductive model for human health

Reproduction. 2012 Jul;144(1):1-10. doi: 10.1530/REP-12-0091. Epub 2012 May 10.

Fischer B, Chavatte-Palmer P, Viebahn C, Navarrete Santos A, Duranthon V. Source Department of Anatomy and Cell Biology, Martin Luther University Faculty of Medicine, Grosse Steinstrasse 52, D-06097 Halle (Saale), Germany.


The renaissance of the laboratory rabbit as a reproductive model for human health is closely related to the growing evidence of periconceptional metabolic programming and its determining effects on offspring and adult health. Advantages of rabbit reproduction are the exact timing of fertilization and pregnancy stages, high cell numbers and yield in blastocysts, relatively late implantation at a time when gastrulation is already proceeding, detailed morphologic and molecular knowledge on gastrulation stages, and a hemochorial placenta structured similarly to the human placenta. To understand, for example, the mechanisms of periconceptional programming and its effects on metabolic health in adulthood, these advantages help to elucidate even subtle changes in metabolism and development during the pre- and peri-implantation period and during gastrulation in individual embryos. Gastrulation represents a central turning point in ontogenesis in which a limited number of cells program the development of the three germ layers and, hence, the embryo proper. Newly developed transgenic and molecular tools offer promising chances for further scientific progress to be attained with this reproductive model species.

PMID 22580370

Rabbit whole embryo culture

Methods Mol Biol. 2012;889:239-52.

Marshall VA, Carney EW. Source Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI, USA.


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. In rabbit WEC, early somite stage embryos (gestation day 9) enclosed within an intact amnion and attached to the visceral yolk sac are dissected from maternal tissues and placed in culture for up to 48 h at approximately 37°C and are continuously exposed to an humidified gas atmosphere mixture in a rotating culture system. 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. Following completion of the culture period, embryos are evaluated based on several growth and development parameters and also are assessed for morphological abnormalities. The ability to sustain embryo development independent of the maternal system allows for exposure at precise development stages providing the opportunity study the direct action of a teratogen or one of its metabolites on the developing embryo. Rabbit WEC is perhaps most useful when used in conjunction with rodent WEC methods to investigate species-specific mechanisms of developmental toxicity.

PMID 22669668


Planar cell movements and oriented cell division during early primitive streak formation in the mammalian embryo

Dev Dyn. 2011 Aug;240(8):1905-16. doi: 10.1002/dvdy.22687.

Halacheva V, Fuchs M, Dönitz J, Reupke T, Püschel B, Viebahn C. Source Department of Anatomy and Embryology, Centre of Anatomy, University of Göttingen, Germany. Abstract Formation of the mammalian primitive streak appears to rely on cell proliferation to a minor extent only, but compensating cell movements have not yet been directly observed. This study analyses individual cell migration and proliferation simultaneously, using multiphoton and differential interference contrast time-lapse microscopy of late pregastrulation rabbit blastocysts. Epiblast cells in the posterior gastrula extension area accumulated medially and displayed complex planar movements including U-turns and a novel type of processional cell movement. In the same area metaphase plates tended to be aligned parallel to the anterior-posterior axis, and statistical analysis showed that rotations of metaphase plates causing preferred orientation were near-complete 8 min before anaphase onset; in some cases, rotations were strikingly rapid, achieving up to 45° per min. The mammalian primitive streak appears to be formed initially with its typically minimal anteroposterior elongation by a combination of oriented cell divisions with dedicated planar cell movements. Copyright © 2011 Wiley-Liss, Inc.

PMID 21761476


Germ layer differentiation during early hindgut and cloaca formation in rabbit and pig embryos

J Anat. 2010 Dec;217(6):665-78. doi: 10.1111/j.1469-7580.2010.01303.x. Epub 2010 Sep 28.

Hassoun R, Schwartz P, Rath D, Viebahn C, Männer J. Source Department of Anatomy and Embryology, Göttingen University, Göttingen, Germany.


Relative to recent advances in understanding molecular requirements for endoderm differentiation, the dynamics of germ layer morphology and the topographical distribution of molecular factors involved in endoderm formation at the caudal pole of the embryonic disc are still poorly defined. To discover common principles of mammalian germ layer development, pig and rabbit embryos at late gastrulation and early neurulation stages were analysed as species with a human-like embryonic disc morphology, using correlative light and electron microscopy. Close intercellular contact but no direct structural evidence of endoderm formation such as mesenchymal-epithelial transition between posterior primitive streak mesoderm and the emerging posterior endoderm were found. However, a two-step process closely related to posterior germ layer differentiation emerged for the formation of the cloacal membrane: (i) a continuous mesoderm layer and numerous patches of electron-dense flocculent extracellular matrix mark the prospective region of cloacal membrane formation; and (ii) mesoderm cells and all extracellular matrix including the basement membrane are lost locally and close intercellular contact between the endoderm and ectoderm is established. The latter process involves single cells at first and then gradually spreads to form a longitudinally oriented seam-like cloacal membrane. These gradual changes were found from gastrulation to early somite stages in the pig, whereas they were found from early somite to mid-somite stages in the rabbit; in both species cloacal membrane formation is complete prior to secondary neurulation. The results highlight the structural requirements for endoderm formation during development of the hindgut and suggest new mechanisms for the pathogenesis of common urogenital and anorectal malformations. © 2010 The Authors. Journal of Anatomy © 2010 Anatomical Society of Great Britain and Ireland.

PMID 20874819


Continuous observation of rabbit preimplantation embryos in vitro by using a culture device connected to a microscope

J Am Assoc Lab Anim Sci. 2009 Jan;48(1):52-6.

Sultana F, Hatori M, Shimozawa N, Ebisawa T, Sankai T.

Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki, Japan. Abstract We developed a compact culture device that maintains developing embryos in vitro under constant temperature and CO(2) concentration. Using this device, we cultured rabbit embryos from the pronuclear stage to the hatched blastocyst stage and recorded their development digitally for 7 d. Recorded images were converted to a movie, and the developmental movement of individual embryos was analyzed. With this culture system, we can observe embryonic development in a suitable environment continuously for several days; similar long-term observation is not possible in the conventional system. The proportion of embryos that developed from the pronuclear stage to the blastocyst stage was the same in the new system (73.1%; 38 of 52) as in the conventional (control) system (77.6%; 38 of 49). Compaction of embryos occurred from the 8-cell to the morula stage at 32.5 +/- 0.71 h after insemination. The time of blastocyst formation (77.2 +/- 3.2 h after insemination) varied somewhat between embryos. Average hatching time was 98.7 +/- 4.4 h after mating. Therefore, the cleavage, blastomere movement, and hatching processes of blastocysts can be followed clearly and recorded by using this new culture system.

PMID: 19245751


Isolation and culture of rabbit primordial germ cells

J Reprod Dev. 2008 Oct;54(5):352-7. Epub 2008 Jul 16.

Kakegawa R, Teramura T, Takehara T, Anzai M, Mitani T, Matsumoto K, Saeki K, Sagawa N, Fukuda K, Hosoi Y.

Graduate School of Biology-Oriented Science and Technology, Kinki University, Wakayama, Japan. Abstract Primordial germ cells (PGCs) are embryonic precursors of the gametes of adult animals and are considered stem cells of the germline. Since their proliferation in vitro correlates well with the schedule of developmental changes in vivo, they might be interesting research tools for genomic imprinting, germ-cell tumors and fertility. Furthermore, once primordial germ cells are separated and placed on a feeder layer with cytokines, they become cultured pluripotent cell lines called embryonic germ (EG) cells. EG cells share several important characteristics with embryonic stem (ES) cells as they can also contribute to the germ line of chimeras. To investigate the characteristics of PGCs and establish rabbit EG (rEG) cells, we cultured rabbit PGCs (rPGCs) in vitro with various combinations of leukemia inhibitory factor (LIF), basic fibroblast growth factor (bFGF) and forskolin on inactivated mouse embryonic fibroblast (MEF) feeder layers. The present study found PGC proliferation in early cultures and induction of rEG-like colonies. These cells expressed pluripotent markers, such as alkaline phosphatase activity, OCT-4, Sox-2 and SSEA-1, in the undifferentiated state; however, the cells did not develop into a teratoma when injected into the kidney capsules of SCID mice, although the restricted differentiation potentials to neural cells were determined via embryoid body formation. From these characteristics and further characterization of the germ stem cell markers Vasa, SCP-1 and SCP-3, we suggested that these were hybrid cells with characteristics somewhere between PGC and EG cells.

PMID: 18628591

Inositol transport in preimplantation rabbit embryos: effects of embryo stage, sodium, osmolality and metabolic inhibitors

Warner SM, Conlon FV, Kane MT. Reproduction. 2003 Apr;125(4):479-93. Erratum in: Reproduction. 2005 Jan;129(1):128. PMID: 12683919

Neurulation in the rabbit embryo

Peeters MC, Viebahn C, Hekking JW, van Straaten HW. Anat Embryol (Berl). 1998 Mar;197(3):167-75. PMID: 9543335

"Among a broad range of factors and mechanisms involved in the complex process of neurulation a relationship between the curvature of the craniocaudal body axis and rate of neural tube closure has been proposed, but more examples and models are needed to further substantiate the existence of this relationship. This is particularly true for mammals, where marked differences in embryonic body curvature between species exist. The rabbit embryo has virtually no curvature during the main phase of neurulation and is therefore a suitable model, but neurulation is hardly documented in this species. In the present study, therefore, neural tube closure in the rabbit embryo is presented in detail by morphological and morphometrical parameters, as well as from scanning electron microscopic investigations. At the stages of 6-8 somites, the flat neural plate transforms into a V-shaped neural groove, beginning at the rhombo-cervical level. Between the stages of 8 and 9 somites, multiple closure sites occur simultaneously at three levels: at the incipient pros-mesencephalic transition, at the incipient mes-rhombencephalic transition, and at the level of the first pairs of somites. This results in four transient neuropores. The anterior and rhombencephalic neuropores close between the stages of 9-11 somites. The mesencephalic neuropore is very briefly present. The posterior neuropore is the largest and remains longest. Its tapered (cranial) portion closes fast within somite stages 9-10. Subsequently its wide (caudal) portion closes up to a narrow slit, but further closure slows down till full closure is achieved at the 22-somite stage. In comparing rabbit neurulation with that of chick and mouse, the 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."
  • rabbit embryo has virtually no curvature during the main phase of neurulation
  • 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 and rhombencephalic neuropores close between the stages of 9-11 somites.
  • The mesencephalic neuropore is very briefly present.
  • The posterior neuropore is the largest and remains longest. Its tapered (cranial) portion closes fast within somite stages 9-10. Subsequently its wide (caudal) portion closes up to a narrow slit, but further closure slows down till full closure is achieved at the 22-somite stage.

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


LEWIS, F. T.: The Development of the Veins in the Limbs of Rabbit Embryos. Am. Jour, of Anat. Vol. V, 1906.