Human Reproduction, Vol. 15, No. suppl_2, pp. 112-128, 2000
© 2000 European Society of Human Reproduction and Embryology
Germline passage of mitochondria: quantitative considerations and possible embryological sequelae
Sydney IVF and the University of Sydney
Correspondence: 1To whom correspondence should be addressed at: Sydney IVF, 4 O'Connell Street, Sydney 2000, Australia. E-mail: robert{at}jansen.com.au
Using a semi-quantitative review of published electron micrographs, we have explored the passage of mitochondria from one generation to the next through the cytoplasm of the human female germ cell. We propose a testable hypothesis that the mitochondria of the germline are persistently ‘haploid’ (effectively carrying just one mitochondrial chromosome per organelle). For mitochondria, the passage through germ cell differentiation, oogenesis, follicle formation and loss could constitute a restriction/amplification/constraint event of a type previously demonstrated for asexual purification and refinement of a nonrecombining genome. At the restriction event (or ‘bottleneck’) in the human primordial germ cell, which differentiates in embryos after gastrulation, there appear to be <10 mitochondria per cell. From 
100 or so such cells, a population of 
7x1O6 oogonia and primary oocytes is produced in the fetal ovaries during mid-gestation, with mitochondria numbering up to 10 000 per cell, implying a massive amplification of the mitochondrial genome. A further 10-fold or greater increase in mitochondrial numbers per oocyte occurs during adult follicular growth and development, as resting primordial follicles develop to pre- ovulatory maturity. So few are the numbers of oocytes that fertilize and successfully cleave to form an embryo of the new generation, that biologists have long suspected that a competitive constraint lies behind the generational completion of this genetic cycle. I propose that maintaining the integrity of mitochondrial inheritance is such a strong evolutionary imperative that features of ovarian follicular formation, function, and loss could be expected to have been primarily adapted to this special purpose. To extend the hypothesis further, the imperative of maintaining mitochondrial genomic integrity in a population could explain why women normally become sterile a number of years before there is depletion of ovarian follicles and endocrine ovarian failure (i.e. why there is ‘an oopause’ preceding the menopause). Plausible explanations might also follow for several well-known and puzzling reproductive difficulties, including recurrent miscarriage, unexplained infertility, and persistent failure of IVF embryos to cleave or to implant. Current experimental laboratory manoeuvres that might circumvent mitochondrial shortcomings (such as cytoplasmic transfusion and karyoplast exchange) are examined and possible clinical hazards identified.
Key words: inheritance/mitochondria/mito-chondrial DNA/oocyte/primordial germ cell
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Ramalho-Santos, S. Varum, S. Amaral, P. C. Mota, A. P. Sousa, and A. Amaral Mitochondrial functionality in reproduction: from gonads and gametes to embryos and embryonic stem cells Hum. Reprod. Update, September 1, 2009; 15(5): 553 - 572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Neiman and D. R Taylor The causes of mutation accumulation in mitochondrial genomes Proc R Soc B, April 7, 2009; 276(1660): 1201 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wilding, G. Coppola, B. Dale, and L. Di Matteo Mitochondria and human preimplantation embryo development Reproduction, April 1, 2009; 137(4): 619 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Torricelli, G. De Falco, P. Florio, M. Rossi, E. Leucci, P. Vigano, L. Leoncini, and F. Petraglia Secretory endometrium highly expresses urocortin messenger RNA and peptide: possible role in the decidualization process Hum. Reprod., January 1, 2007; 22(1): 92 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Malik, K. Day, I. Perrault, D.S. Charnock-Jones, and S. K. Smith Reduced levels of VEGF-A and MMP-2 and MMP-9 activity and increased TNF-{alpha} in menstrual endometrium and effluent in women with menorrhagia Hum. Reprod., August 1, 2006; 21(8): 2158 - 2166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A L Frederiksen, P H Andersen, K O Kyvik, T D Jeppesen, J Vissing, and M Schwartz Tissue specific distribution of the 3243A->G mtDNA mutation J. Med. Genet., August 1, 2006; 43(8): 671 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Thouas, A. O. Trounson, and G. M. Jones Developmental Effects of Sublethal Mitochondrial Injury in Mouse Oocytes Biol Reprod, May 1, 2006; 74(5): 969 - 977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Graesslin, A. Cortez, R. Fauvet, M. Lorenzato, P. Birembaut, and E. Darai Metalloproteinase-2, -7 and -9 and tissue inhibitor of metalloproteinase-1 and -2 expression in normal, hyperplastic and neoplastic endometrium: a clinical-pathological correlation study Ann. Onc., April 1, 2006; 17(4): 637 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.J.A.M. Jacobs, G. de Wert, J.P.M. Geraedts, I.F.M. de Coo, and H.J.M. Smeets The transmission of OXPHOS disease and methods to prevent this Hum. Reprod. Update, March 1, 2006; 12(2): 119 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Thouas, A. O. Trounson, and G. M. Jones Effect of Female Age on Mouse Oocyte Developmental Competence Following Mitochondrial Injury Biol Reprod, August 1, 2005; 73(2): 366 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Roze, F. Rousset, and Y. Michalakis Germline Bottlenecks, Biparental Inheritance and Selection on Mitochondrial Variants: A Two-Level Selection Model Genetics, July 1, 2005; 170(3): 1385 - 1399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pineau, M. Henry, R. Suspene, A. Marchio, A. Dettai, R. Debruyne, T. Petit, A. Lecu, P. Moisson, A. Dejean, et al. A Universal Primer Set for PCR Amplification of Nuclear Histone H4 Genes from All Animal Species Mol. Biol. Evol., March 1, 2005; 22(3): 582 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Thouas, A. O. Trounson, E. J. Wolvetang, and G. M. Jones Mitochondrial Dysfunction in Mouse Oocytes Results in Preimplantation Embryo Arrest in Vitro Biol Reprod, December 1, 2004; 71(6): 1936 - 1942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Van Blerkom Mitochondria in human oogenesis and preimplantation embryogenesis: engines of metabolism, ionic regulation and developmental competence Reproduction, September 1, 2004; 128(3): 269 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Coppock, A. White, J. D. Aplin, and M. Westwood Matrix Metalloprotease-3 and -9 Proteolyze Insulin-Like Growth Factor-Binding Protein-1 Biol Reprod, August 1, 2004; 71(2): 438 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Passamonti, J. L. Boore, and V. Scali Molecular Evolution and Recombination in Gender-Associated Mitochondrial DNAs of the Manila Clam Tapes philippinarum Genetics, June 1, 2003; 164(2): 603 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hickey and I.S. Fraser Surface vascularization and endometrial appearance in women with menorrhagia or using levonorgestrel contraceptive implants. Implications for the mechanisms of breakthrough bleeding Hum. Reprod., September 1, 2002; 17(9): 2428 - 2434. [Abstract] [Full Text] [PDF]
|
|