Skip to main content
Log in

The potential significance of binovular follicles and binucleate giant oocytes for the development of genetic abnormalities

  • Review Article
  • Published:
Journal of Genetics Aims and scope Submit manuscript

Abstract

Normal development of a fertilizable female gamete emanates from a follicle containing only one oocyte that becomes haploid after first meiotic division. Binovular follicles including two oocytes and binucleate giant oocytes that are diploid after first meiosis constitute notable exceptions from this rule. Data provided by programmes of human-assisted reproduction on the occurrence of both phenomena have been reviewed to evaluate possible implications for the formation of genetic abnormalities. To exclude confusion with oocytes aspirated from two adjacent individual follicles, true binovularity has been defined as inclusion of two oocytes within a common zona pellucida or their fusion in the zonal region. A total of 18 conjoined oocytes have been reported and one of the oocyte was normally fertilized in seven cases. Simultaneous fertilization of both female gametes occurred only once. No pregnancy was achieved after transfer of an embryo from a binovular follicle. Binucleate giant oocytes have been observed sporadically but a few reports suggest an incidence of up to 0.3% of all gametes retrieved. Extensive studies performed by two independent centres demonstrated that giant oocytes are diploid at metaphase II, can undergo fertilization in vitro with formation of two or three pronuclei and develop into triploid zygotes and triploid or triploid/mosaic embryos. In summary, giant binucleate oocytes may be responsible for the development of digynic triploidy whereas the currently available data do not support a role of conjoined oocytes in producing dizygotic twins, mosaicism, chimaeras or tetraploidy. However, more information on the maturity and fertilizability of oocytes from binovular follicles is needed. Future studies should also evaluate a possible impact of pharmaceutical and environmental oestrogens on the formation of multiovular follicles.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1.

Similar content being viewed by others

References

  • Al-Mufti W., Bomsel-Helmreich O. and Christidès J. P. 1988 Oocyte size and intrafollicular position in polyovular follicles in rabbits. J. Reprod. Fertil. 82, 15–25.

    Article  PubMed  CAS  Google Scholar 

  • Aoki R., Honma Y., Yada Y., Momoi M. and Iwamoto S. 2006 Blood chimerism in monochorionic twins conceived by induced ovulation: Case report. Hum. Reprod. 21, 735–737.

    Article  PubMed  Google Scholar 

  • Austin C. R. 1960 Anomalies of fertilization leading to triploidy. J. Cell. Comp. Physiol. 56, suppl. 1, 1–15.

    Article  PubMed  Google Scholar 

  • Balakier H., Bouman D., Sojecki A., Librach C. and Squire J. 2002 Morphological and cytogenetic analysis of human giant oocytes and giant embryos. Hum. Reprod. 17, 2394–2401.

    Article  PubMed  Google Scholar 

  • Ben-Rafael Z., Mastroianni L. and Kopf G. S. 1987 In vitro fertilization and cleavage of a single egg from a binovular follicle containing two individual eggs surrounded by a single zona pellucida. Fertil. Steril. 47, 707–709.

    PubMed  CAS  Google Scholar 

  • Boklage C. E. 2009 Traces of embryogenesis are the same in monozygotic and dizygotic twins: not compatible with double ovulation. Hum. Reprod. 24, 1255–1266.

    Article  PubMed  Google Scholar 

  • Collins D. C. and Kent Jr H. A. 1964 Polynuclear ova and polyovular follicles in the ovaries of young guinea pigs. Anat. Rec. 148, 115–119.

    Article  PubMed  CAS  Google Scholar 

  • Dandekar P. V., Martin M. C. and Glass R. H. 1988 Polyovular follicles associated with human in vitro fertilization. Fertil. Steril. 49, 483–486.

    PubMed  CAS  Google Scholar 

  • Edwards R. G. and Fowler R. E. 1970 The genetics of human pre-implantation development. In Modern trends in human genetics 1 (ed. A. E. H. Emery), pp. 181–213. Butterworths, London, UK.

  • Fishel S., Kaufman M. H., Jackson P., Webster J. and Faratian B. 1989 Recovery of two human oocytes surrounded by a single zona pellucida. Fertil. Steril. 52, 325–327.

    PubMed  CAS  Google Scholar 

  • Funaki K. and Mikamo K. 1980 Giant diploid oocytes as a cause of digynic triploidy in mammals. Cytogenet. Cell. Genet. 28, 158–168.

    Article  PubMed  CAS  Google Scholar 

  • Gougeon A. 1981 Frequent occurrence of multiovular follicles and multinuclear oocytes in the adult human ovary. Fertil. Steril. 35, 417–422.

    PubMed  CAS  Google Scholar 

  • Grau N., Escrich L., Martín J., Rubio C., Pellicer A. and Escribá M.-J. 2011 Self-correction in tripronucleated human embryos. Fertil. Steril. 96, 951–956.

    Article  PubMed  Google Scholar 

  • Guillette Jr L. J. and Moore B. C. 2006 Environmental contaminants, fertility, and multioocytic follicles: a lesson from wildlife? Semin. Reprod. Med. 24, 134–141.

    Article  PubMed  CAS  Google Scholar 

  • Hartman C. G. 1926 Polynuclear ova and polyovular follicles in the opossum and other mammals with special reference to the problem of fecundity. Am. J. Anat. 37, 1–51.

    Article  Google Scholar 

  • Hartshorne G. M., Blayney M., Dyson H. and Elder K. 1990 In vitro fertilization and development of one of two human oocytes with fused zonae pellucidae: case report. Fertil. Steril. 54, 947–949.

    PubMed  CAS  Google Scholar 

  • Iguchi T., Fukazawa Y., Uesugi Y. and Takasugi N. 1990 Polyovular follicles in mouse ovaries exposed neonatally to diethylstilbestrol in vivo and in vitro. Biol. Reprod. 43, 478–484.

    Article  PubMed  CAS  Google Scholar 

  • Jones G. S. 1968 Induction of ovulation. Annu. Rev. Med. 19, 351–372.

    Article  PubMed  CAS  Google Scholar 

  • Kennedy J. P. and Donahue R. P. 1969 Binucleate human oocytes from large follicles. Lancet 1, 754–755.

    Article  PubMed  CAS  Google Scholar 

  • Kent Jr H. A. 1960 Polyovular follicles and multinucleate ova in the ovaries of young mice. Anat. Rec. 137, 521–524.

    Article  PubMed  Google Scholar 

  • Kent Jr H. A. 1962a Polyovular follicles and multinucleate ova in the ovaries of young rats. Anat. Rec. 142, 25–29.

    Article  PubMed  Google Scholar 

  • Kent Jr H. A. 1962b Polyovular follicles and multinucleate ova in the ovaries of young hamsters. Anat. Rec. 143, 345–349.

    Article  PubMed  Google Scholar 

  • Kousehlar M., Allgayer G., Daufratshofer C., Haseitl M. and Felberbaum R. 2009 An egg with double yolk. The phenomenon of binovular zona pellucida. Gynäkol. Endokrinol. 7, 190 (in German).

    Article  Google Scholar 

  • Machtinger R., Politch J. A., Hornstein M. D., Ginsburg E. S. and Racowsky C. 2011 A giant oocyte in a cohort of retrieved oocytes: does it have any effect on the in vitro fertilization cycle outcome? Fertil. Steril. 95, 573–576.

    Article  PubMed  Google Scholar 

  • Manivel J. C., Dehner L. P. and Burke B. 1988 Ovarian tumorlike structures, biovular follicles, and binucleated oocytes in children: their frequency and possible pathologic significance. Pediatr. Pathol. 8, 283–292.

    Article  PubMed  CAS  Google Scholar 

  • Munné S., Alikani M. and Cohen J. 1994 Monospermic polyploidy and atypical embryo morphology. Hum. Reprod. 9, 506–510.

    PubMed  Google Scholar 

  • Muretto P., Chilosi M., Rabitti C., Tommasoni S. and Colato C. 2001 Biovularity and “coalescence of primary follicles” in ovaries with mature teratomas. Int. J. Surg. Pathol. 9, 121–125.

    Article  PubMed  CAS  Google Scholar 

  • Papadaki L. 1978 Binovular follicles in the adult human ovary. Fertil. Steril. 29, 342–350.

    PubMed  CAS  Google Scholar 

  • Payan-Carreira R. and Pires M. A. 2008 Multioocyte follicles in domestic dogs: a survey of frequency of occurrence. Theriogenology 69, 977–982.

    Article  PubMed  CAS  Google Scholar 

  • Reynaud K., Halter S., Tahir Z., Thoumire S., Chebrout M. and Chastant-Maillard S. 2010 Polyovular follicles. Gynecol. Obstet. Fertil. 38, 395–397 (in French).

    Article  PubMed  CAS  Google Scholar 

  • Rivera O. E., Varayoud J., Rodríguez H. A., Muñoz-de-Toro M. and Luque E. H. 2011 Neonatal exposure to bisphenol A or diethylstilbestrol alters the ovarian follicular dynamics in the lamb. Reprod. Toxicol. 32, 304–312.

    Article  PubMed  CAS  Google Scholar 

  • Rodríguez H. A., Santambrosio N., Santamaría C. G., Muñoz-de-Toro M. and Luque E. H. 2010 Neonatal exposure to bisphenol A reduces the pool of primordial follicles in the rat ovary. Reprod. Toxicol. 30, 550–557.

    Article  PubMed  Google Scholar 

  • Ron-El R., Nachum H., Golan A., Herman A., Yigal S. and Caspi E. 1990 Binovular human ovarian follicles associated with in vitro fertilization: incidence and outcome. Fertil. Steril. 54, 869–872.

    PubMed  CAS  Google Scholar 

  • Rosenbusch B. 2008 Mechanisms giving rise to triploid zygotes during assisted reproduction. Fertil. Steril. 90, 49–55.

    Article  PubMed  Google Scholar 

  • Rosenbusch B. 2009 Selective microsurgical removal of a pronucleus from tripronuclear human oocytes to restore diploidy: disregarded but valuable? Fertil. Steril. 92, 897–903.

    Article  PubMed  Google Scholar 

  • Rosenbusch B. 2010 A preliminary concept, deduced from cytogenetic analyses, for explaining different types of multipronuclear oocytes obtained after ICSI. Fertil. Steril. 94, 2479–2481.

    Article  PubMed  Google Scholar 

  • Rosenbusch B. and Schneider M. 2004 A brief look at the origin of tetraploidy. Cytogenet. Genome Res. 107, 128–131.

    Article  PubMed  CAS  Google Scholar 

  • Rosenbusch B. and Hancke K. 2012 Conjoined human oocytes observed during assisted reproduction: description of three cases and review of the literature. Rom. J. Morphol. Embryol. 53, 189–192.

    PubMed  CAS  Google Scholar 

  • Rosenbusch B. E. and Schneider M. 2009 Separation of a pronucleus by premature cytokinesis: a mechanism for immediate diploidization of tripronuclear oocytes? Fertil. Steril. 92, 394.e5–394.e8.

    Article  Google Scholar 

  • Rosenbusch B., Schneider M., Glaeser B. and Brucker C. 2002 Cytogenetic analysis of giant oocytes and zygotes to assess their relevance for the development of digynic triploidy. Hum. Reprod. 17, 2388–2393.

    Article  PubMed  CAS  Google Scholar 

  • Safran A., Reubinoff B. E., Porat-Katz A., Werner M., Friedler S. and Lewin A. 1998 Intracytoplasmic sperm injection allows fertilization and development of a chromosomally balanced embryo from a binovular zona pellucida. Hum. Reprod. 13, 2575–2578.

    Article  PubMed  CAS  Google Scholar 

  • Sherrer C. W., Gerson B. and Woodruff J. D. 1977 The incidence and significance of polynuclear follicles. Am. J. Obstet. Gynecol. 128, 6–12.

    PubMed  CAS  Google Scholar 

  • Shettles L. B. 1981 Polynuclear oocytes and polyovular follicles. Fertil. Steril. 36, 539.

    PubMed  CAS  Google Scholar 

  • Stankiewicz T., Błaszczyk B. and Udała J. 2009 A study on the occurrence of polyovular follicles in porcine ovaries with particular reference to intrafollicular hormone concentrations, quality of oocytes and their in vitro fertilization. Anat. Histol. Embryol. 38, 233–239.

    Article  PubMed  CAS  Google Scholar 

  • Telfer E. and Gosden R. G. 1987 A quantitative cytological study of polyovular follicles in mammalian ovaries with particular reference to the domestic bitch (Canis familiaris). J. Reprod. Fertil. 81, 137–147.

    Article  PubMed  CAS  Google Scholar 

  • Thompson R. S. and Zamboni L. 1975 Anomalous patterns of mammalian oocyte maturation and fertilization. Am. J. Anat. 142, 233–263.

    Article  PubMed  CAS  Google Scholar 

  • Uebele-Kallhardt B. and Knoerr K. 1975 Oocytes from polycystic human ovaries. Arch. Gynaekol. 218, 189–201 (in German).

    Article  CAS  Google Scholar 

  • Veeck L. L. 1999 An atlas of human gametes and conceptuses. Parthenon Publishing, Casterton Hall, UK.

    Google Scholar 

  • Vicdan K., Işik A. Z., Daðli H. G., Kaba A. and Kişnişçi H. 1999 Fertilization and development of a blastocyst-stage embryo after selective intracytoplasmic sperm injection of a mature oocyte from a binovular zona pellucida: a case report. J. Assist. Reprod. Genet. 16, 355–357.

    Google Scholar 

  • Zaragoza M. V., Surti U., Redline R. W, Millie E., Chakravarti A. and Hassold T. J. 2000 Parental origin and phenotype of triploidy in spontaneous abortions: predominance of diandry and association with the partial hydatidiform mole. Am. J. Hum. Genet. 66, 1807–1820.

    Article  PubMed  CAS  Google Scholar 

  • Zeilmaker G. H., Alberda A. T. and van Gent I. 1983 Fertilization and cleavage of oocytes from a binovular human ovarian follicle: a possible cause of dizygotic twinning and chimerism. Fertil. Steril. 40, 841–843.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bernd Rosenbusch.

Additional information

[Rosenbusch B. 2012 The potential significance of binovular follicles and binucleate giant oocytes for the development of genetic abnormalities. J. Genet. 91, xx–xx]

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rosenbusch, B. The potential significance of binovular follicles and binucleate giant oocytes for the development of genetic abnormalities. J Genet 91, 397–404 (2012). https://doi.org/10.1007/s12041-012-0195-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12041-012-0195-x

Keywords

Navigation