Chemotherapy-induced late transgenerational effects in mice

To our knowledge, there is no report on long-term reproductive and developmental side effects in the offspring of mothers treated with a widely used chemotherapeutic drug such as doxorubicin (DXR), and neither is there information on transmission of any detrimental effects to several filial generations. Therefore, the purpose of the present paper was to examine the long-term effects of a single intraperitoneal injection of DXR on the reproductive and behavioral performance of adult female mice and their progeny. C57BL/6 female mice (generation zero; G0) were treated with either a single intraperitoneal injection of DXR (G0-DXR) or saline (G0-CON). Data were collected on multiple reproductive parameters and behavioral analysis for anxiety, despair and depression. In addition, the reproductive capacity and health of the subsequent six generations were evaluated. G0-DXR females developed despair-like behaviors; delivery complications; decreased primordial follicle pool; and early lost of reproductive capacity. Surprisingly, the DXR-induced effects in oocytes were transmitted transgenerationally; the most striking effects being observed in G4 and G6, constituting: increased rates of neonatal death; physical malformations; chromosomal abnormalities (particularly deletions on chromosome 10); and death of mothers due to delivery complications. None of these effects were seen in control females of the same generations. Long-term effects of DXR in female mice and their offspring can be attributed to genetic alterations or cell-killing events in oocytes or, presumably, to toxicosis in non-ovarian tissues. Results from the rodent model emphasize the need for retrospective and long-term prospective studies of survivors of cancer treatment and their offspring.


Epigenetic mechanisms regulate MHC and antigen processing molecules in human embryonic and induced pluripotent stem cells

Epigenetic mechanisms regulate MHC and antigen processing molecules in human embryonic and induced pluripotent stem cells. Suárez-Alvarez B, Rodriguez RM, Calvanese V, Blanco-Gelaz MA, Suhr ST, Ortega F, Otero J, Cibelli JB, Moore H, Fraga MF, López-Larrea C. PLoS One. 2010 Apr 16;5(4):e10192.


Original Reports

Reprogrammed transcriptome in rhesus-bovine interspecies somatic cell nuclear transfer embryos.

Wang K, Otu HH, Chen Y, Lee Y, Latham K, Cibelli JB PLoS One. 2011;6(7):e22197.


Downregulation of H19 Improves the Differentiation Potential of Mouse Parthenogenetic Embryonic Stem Cells.

Ragina NP, Schlosser K, Knott JG, Senagore PK, Swiatek PJ, Chang EA, Fakhouri WD, Schutte BC, Kiupel M, Cibelli JB      Stem Cells Dev. 2011 Sep 14.


Generation of Leukemia Inhibitory Factor and Basic Fibroblast Growth Factor-Dependent Induced Pluripotent Stem Cells from Canine Adult Somatic Cells

Luo J, Suhr ST, Chang EA, Wang K, Ross PJ, Nelson LL, Venta PJ, Knott JG, Cibelli JB Stem Cells Dev. 2011 Jun 15.

Chemotherapy-induced late transgenerational effects in mice

Kujjo LL, Chang EA, Pereira RJ, Dhar S, Marrero-Rosado B, Sengupta S, Wang H, Cibelli JB, Perez GI  PLoS One. 2011 Mar 17;6(3):e17877.

Mitochondrial rejuvenation after induced pluripotency

Suhr ST, Chang EA, Tjong J, Alcasid N, Perkins GA, Goissis MD, Ellisman MH, Perez GI, Cibelli JB      PLoS One. 2010 Nov 23;5(11):e14095.

Housekeeping gene transcript abundance in bovine fertilized and cloned embryos.

Ross PJ, Wang K, Kocabas A, Cibelli JB Cell Reprogram. 2010 Dec;12(6):709-17. Epub 2010 Oct 25.

Epigenetic mechanisms regulate MHC and antigen processing molecules in human embryonic and induced pluripotent stem cells

Suárez-Alvarez B, Rodriguez RM, Calvanese V, Blanco-Gelaz MA, Suhr ST, Ortega F, Otero J, Cibelli JB, Moore H, Fraga MF, López-Larrea C      PLoS One. 2010 Apr 16;5(4):e10192.

Human-induced pluripotent stem cells produced under xeno-free conditions

Ross PJ, Suhr ST, Rodriguez RM, Chang EA, Wang K, Siripattarapravat K, Ko T, Cibelli JB Stem Cells Dev. 2010 Aug;19(8):1221-9

The influence of donor nucleus source on the outcome of zebrafish somatic cell nuclear transfer

Siripattarapravat K, Pinmee B, Chang EA, Muñoz JD, Kawakami K, Cibelli JB      Int J Dev Biol. 2010;54(11-12):1679-83.

Dynamic epigenetic regulation of the Oct4 and Nanog regulatory regions during neural differentiation in rhesus nuclear transfer embryonic stem cells

Wang K, Chen Y, Chang EA, Knott JG, Cibelli JB      Cloning Stem Cells. 2009 Dec;11(4):483-96.


Somatic cell nuclear transfer in zebrafish

Siripattarapravat K, Pinmee B, Venta PJ, Chang CC, Cibelli JB      Nature Methods. 2009 Oct;6(10):733-5.


Characterization and in vitro control of MPF activity in zebrafish eggs

Siripattarapravat K, Busta A, Steibel JP, Cibelli JB. 2009       Zebrafish. 2009 Mar;6(1):97-105.


Bovine ooplasm partially remodels primate somatic nuclei following somatic cell nuclear transfer.

Wang K, Beyhan Z, Rodriguez RM, Ross PJ, lager AE, Kaiser GG, Chen Y, and Cibelli JB      Cloning and Stem Cells. 2009 Mar;11(1):187-202.


Activation of bovine somatic cell nuclear transfer embryos by PLCZ cRNA injection

Ross P, Rodriguez R, Iager A, Beyhan Z, Wang K, Ragina N, Yoon SY, Fissore R, Cibelli JB.


Production of recombinant albumin by a herd of cloned transgenic cattle

Echelard Y, Williams JL, Destrempes MM, Koster JA, Overton SA, Pollock DP, Rapiejko KT, Behboodi E, Masiello NC, Gavin WG, Pommer J, Van Patten SM, Faber DC, Cibelli JB, Meade HM      Transgenic Res. 2009 Jun;18(3):361-76. Epub 2008 Nov 22.

Human sperm devoid of PLC, zeta 1 fail to induce Ca(2+) release and are unable to initiate the first step of embryo development

Yoon SY, Jellerette T, Salicioni AM, Lee HC, Yoo MS, Coward K, Parrington J, Grow D, Cibelli JB, Visconti PE, Mager J, Fissore RA. 
J Clin Invest. 2008 Nov;118(11):3671-81.


Polycomb gene expression and histone H3 lysine 27 trimethylation changes during bovine preimplantation development

Ross PJ, Ragina NP, Rodriguez RM, Iager AE, Siripattarapravat K, Lopez-Corrales N, Cibelli JB.
Reproduction. 2008 Dec;136(6):777-85.

Trichostatin A Improves Histone Acetylation in Bovine Somatic Cell Nuclear Transfer Early Embryos

Iager AE, Ragina NP, Ross PJ, Beyhan Z, Cunniff K, Rodriguez RM, Cibelli JB Cloning Stem Cells. 2008 Sep;10(3):371-9.


Parthenogenetic activation of bovine oocytes using bovine and murine phospholipase C zeta

Ross PJ, Beyhan Z, Iager AE, Yoon SY, Malcuit C, Schellander K, Fissore RA, Cibelli JB BMC Dev Biol. 2008 Feb 19;8:16.


Development. Is therapeutic cloning dead?

Cibelli JB      Science 2007 Dec 21;318(5858):1879-80

Human parthenogenetic blastocysts derived from noninseminated cryopreserved human oocytes

Polak de Fried E, Ross PJ, Zang G, Divita A, Cunniff K, Denaday F, Salamone D, Kiessling A, Cibelli J      Fertil Steril. 2007 Aug 11 [Epub ahead of print]


Developmental Biology. A decade of cloning mystique

Cibelli JB      Science, 2007 May 18;316(5827):990-2


Transcriptional reprogramming of somatic cell nuclei during preimplantation development of cloned bovine embryos

Beyhan Z, Ross JP, Iager AE, Kocabas AM, Rosa GJ, Cibelli JB      Dev Biol, 2007 May 15;305(2):637-49. Epub 2007 Feb 7


Oocyte spontaneous activation in different rat strains

Ross JP, Yabuuchi A, Cibelli JB Cloning Stem Cells, 2006 Winter;8(4):275-82


Full developmental potential of mammalian preimplantation embryos is maintained after imaging using a spinning-disk confocal microscope
Ross JP, Perez GI, Ko T, Yoo MS, Cibelli JB
Biotechniques, 2006 Dec;41(6):741-50


The Transcriptome of Human Oocytes
(Click Here to Access the SUPPLEMENTARY DATA SET) 
Kocabas AM, Crosby J, Ross PJ, Otu HH, Beyhan Z, Can H, Tam WL, Rosa GJM, Halgren RG, Lim B, Fernandez E, Cibelli JB
PNAS, September 19, 2006. 103 (38):14027-14032


Effect of timing of the removal of oocyte chromosomes before or after injection of somatic nucleus on development of NT embryos.
Wakayama S, Cibelli JB, Wakayama T
Cloning Stem Cells. 2003;5(3):


Nonhuman primate parthenogenetic stem cells
Vrana KE, Hipp J, Goss A, McCool BA, Riddle DR, Walker SJ, Wettstein PJ, Studer LP, Tabar V, Cunniff K, Chapman K, Vilner L, West MD, Grant KA, and Cibelli JB
PNAS, September 22, 2003


Parthenogenetic stem cells in non-human primates
Cibelli JB, Vrana K, Chapman K, Cunniff K, Worst T, Green H, Walker S, Gutin P, Vilner L, Tabar V, Dominko T, Kane J, Wettstein P, Suder L, West MD & Grant K
Science, February 1st 2002.


Somatic Cell Nuclear Transfer in Humans: Pronuclear and Early Embryonic Development
Cibelli JB, Kiessling A, Cunniff K, Richards C, Lanza RP, West MD
e-biomed: The Journal of Regenerative Medicine, Volume 2, 2001, November 26,2001


Cloned Cattle Can Be Healthy and Normal
Lanza RP, Cibelli JB, Faber D, Sweeney RW, Henderson B, Nevala W, West MD, Wettstein PJ
Science 2001 Nov 30;294(5548):1893-4


Placental Abnormalities in a Viable Cloned Calf
Hill JR , Edwards JF, Sawyer N, Blackwell C, and Cibelli JB
Cloning, Vol 3, Number 2, 2001

Cloning of an Endangered Species (Bos guarus) Using Interspecies Nuclear Transfer

Lanza RL, Cibelli JB, Diaz F, Moraes CT, Farin PW, Farin EF, Hammer CJ, West MD, Damiani P      Cloning, 2(2) 2000.


Extension of cell life-span and telomere length in animals cloned from senescent somatic cells

Lanza RP, Cibelli JB, Blackwell C, Cristofalo VJ, Francis MK, Baerlocher GM, Mak J, Schertzer M, Chavez EA, Sawyer N, Lansdorp PM, West MD
Science, 288(5466), 665-669 (2000).


Clinical and Pathological Features of Cloned Transgenic Calves and Fetuses: (13 case study)

Hill JR, Roussel AJ, Cibelli JB, Edwards JF, Hooper NL, Miller MW, Thompson JA, Looney CR, Westhusin ME, Robl JM, Stice SL      Theriogenology 51, 1451-1465 (1999).


Cloned Transgenic Calves Produced from Non-quiescent Fetal Fibroblasts

Cibelli JB, Stice SL, Golueke PJ, Kane J, Jerry J, Blackwell C, F. Ponce de León A. & Robl JM      Science, 280, 1256-1258 (1998).


Transgenic Bovine Chimeric Offspring Produced from Somatic Cell-derived Stem-Like Cells

Cibelli, JB, Stice SL, Golueke PJ, Kane J, Jerry J, Blackwell C, F. Ponce de León A. & Robl JM      Nature Biotechnology, 16, 642-646 (1998).


Somatic cell cloned transgenic bovine neurons for transplantation in parkinsonian rats

Zawada WM(*), Cibelli JB(*), Choi PK, Clarkson ED, Golueke PJ, Witta SE, Bell KP, Kane J, Ponce de León A., Jerry DJ, Robl JM, Freed CR & Stice SL      Nature Medicine, 4, 569-574 (1998).
(*) equal contribution.


Evaluation of developmental competence, nuclear and ooplasmic maturation of calf oocytes

Damiani P, Fissore RA, Cibelli JB, Robl J.M. & Duby RT      Molecular Reproduction & Development 45, 521-534 (1996).



Reviews and Commentaries


Research Priorities: Farm Animal Research in Crisis
Roberts RM, Smith GW, Bazer FW, Cibelli JB, Seidel GE Jr, Bauman DE, Reynolds LP, Ireland JJ.
Science. 2009 Apr 24; 324(5926):468-9


Interspecies nuclear transfer: implications for embryonic stem cell biology  
Beyhan Z, Iager AE, Cibelli JB. 
Cell Stem Cell. 2007 Nov;1(5):502-12. Review


Risk assessment of meat and milk from cloned animals
Yang X, Tian XC, Kubota C, Page R, Xu J, Cibelli J, Seidel G Jr
Nature Biotechnol, 2007 Jan;25(1):77-83

Sperm mediated transgenesis rushes 'Back to the Future' 
Cibelli JB
Mol Ther. 2002 Dec;6(6):699-700.


The health profile of cloned animals
Cibelli JB, Campbell KH, Seidel GE, West MD, Lanza RP
Nat Biotechnol 2002 Jan;20(1):13-4


The ethical validity of using nuclear transfer in human transplantation
Lanza RP, Caplan AL, Silver LM, Cibelli JB, West MD, Green RM.
JAMA 2000 Dec 27;284(24):3175-9


Prospects for the use of nuclear transfer in human transplantation
Lanza RP, Cibelli JB, West MD
Nature Biotechnology 1999 Dec;17(12):1171-4


Human Therapeutic Cloning
Lanza RP, Cibelli JB, West MD
Nature Medicine September 1999.


Cloning cattle in 1998: present and future opportunities
Stice SL and Cibelli JB
Proceeding for American Embryo Transfer Association. San Antonio Texas. October 1998.


New developments in nuclear transfer technology
Stice SL and Cibelli JB
Proceedings of the Annual Meeting Canadian Society of Animal Sciences. July 1998.

Somatic cell nuclear transplantation in cattle. The Cloning symposium: Reprogramming cell fate-transgenesis and cloning
Robl JM, Cibelli JB, Stice SL
The Institute of Reproduction and Development. Melbourne, Australia. April 1998.

Cloning: new breakthroughs leading to commercial opportunities
Stice SL, Robl JM, Ponce de León FA, Jerry J., Golueke PG, Cibelli JB, Kaine JJ
Theriogenology 49:129-138. 1998.



Letters & Popular Science


To the Honorable George W. Bush, President of the United States
The Washington Post
February 21, 2000

Science over Politics
Science, Vol. 283
March 1999

Popular Science

The First Human Cloned Embryo
Cibelli JB, Lanza RP, West M.D
Scientific American January 2002


Books & Book Chapters


“Principles of Cloning”

Jose Cibelli, Editor
Academic Press, 2002



Book Chapters


Bovine Somatic Cell Nuclear Transfer.  

Ross P, Cibelli JB
Methods Molecular Biology - Humana Press, 2010


Parthenogenetic embryonic stem cells in non-human primates 

Ragina NP, Cibelli JB
Trends in Stem Cell Biology and Technology. Humana Press, 2009


Derivation of Embryonic Stem Cells from Parthenogenetic Eggs

Cibelli JB
Emerging Technology Platforms for Stem Cells. Wiley - InterScience, 2009


La clonación terapéutica y reprogramación celular

Rodríguez R, Ross PJ, Cibelli JB
Lopez Larrea C (ed), Del transplante de órganos a las células madre. McGraw-Hill/Interamericana, 2008


Somatic Cell Nuclear Transfer for the Generation of Embryonic Stem Cells

Cibelli JB, Beyhan Z
Principles in Regenerative Medicine -Elsevier Press, San Diego, 2007.


Embryonic stem cells from parthenotes

Cibelli JB
Methods Enzymol. 2006;418:117-35.


Human Therapeutic Cloning

Cibelli JB, Cunniff K, Vrana KE
The Humana Press, 2002


A Historical Perspective of Nuclear Transfer Cloning

Teskin R, Cibelli JB
CABI Publishing, New York, 2002