Free Standard AU & NZ Shipping For All Book Orders Over $80!
Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Booroola BMPR1B mutation alters early follicular development and oocyte ultrastructure in sheep

Karen L. Reader A E , Lisa J. Haydon A , Roger P. Littlejohn B D , Jennifer L. Juengel A and Kenneth P. McNatty C
+ Author Affiliations
- Author Affiliations

A AgResearch, Animal Production, Invermay Agricultural Centre, Private Bag 50034, Mosgiel 9053, New Zealand.

B Bioinformatics, Mathematics and Statistics, Invermay Agricultural Centre, Private Bag 50034, Mosgiel 9053, New Zealand.

C Victoria University of Wellington, School of Biological Sciences, PO Box 600, Wellington 6140, New Zealand.

D Dr Roger Littlejohn died on 6 March 2011.

E Corresponding author. Email: karen.reader@agresearch.co.nz

Reproduction, Fertility and Development 24(2) 353-361 https://doi.org/10.1071/RD11095
Submitted: 14 April 2011  Accepted: 18 July 2011   Published: 2 November 2011

Abstract

Booroola ewes homozygous (BB) for a mutation in the bone morphogenetic protein receptor-1b (BMPR1B) gene exhibit higher ovulation rates, have larger diameter oocytes at earlier stages of follicular development (i.e. Type 3) and smaller diameter follicles at ovulation than wild-type (++) sheep. However, it is not known when BMPR1B is first expressed in the developing ovary or the cell types involved. In addition, the effects of the BMPR1B mutation on primordial (Type 1) follicles or during growth to the Type 3 stage are unknown. In the present study, BB and ++ fetal ovaries at Days 30–135 of gestation were screened by in situ hybridisation for BMPR1B mRNA. Ovaries from BB and ++ lambs were examined by microscopy to measure follicular and oocyte ultrastructural characteristics in Type 1–3 follicles. BMPR1B mRNA was observed in ovaries from Day 35 of gestation and was evident in oocytes of newly forming and fully formed Type 1 follicles. In BB animals, the Type 1 follicles had larger mean follicular and oocyte diameters, a greater volume of mitochondria, smooth endoplasmic reticulum and ribosomes and a greater surface area of junctions with the granulosa cells compared with ++ animals. It is concluded that the BMPR1B mutation alters follicular development from the onset of follicular formation.

Additional keywords: BMPR1B mRNA expression, electron microscopy, mitochondria, ovarian development, ribosomes, smooth endoplasmic reticulum.


References

Bielanska-Osuchowska, Z. (2006). Oogenesis in pig ovaries during the prenatal period: ultrastructure and morphometry. Reprod. Biol. 6, 161–193.
| 17173096PubMed |

Carabatsos, M. J., Elvin, J., Matzuk, M. M., and Albertini, D. F. (1998). Characterization of oocyte and follicle development in growth differentiation factor-9-deficient mice. Dev. Biol. 204, 373–384.
Characterization of oocyte and follicle development in growth differentiation factor-9-deficient mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXmtF2ltA%3D%3D&md5=2bd7e8e0dafe06f4a59763231f0967a6CAS | 9882477PubMed |

Clark, D. E., Tisdall, D. J., Fidler, A. E., and McNatty, K. P. (1996). Localization of mRNA encoding c-kit during the initiation of folliculogenesis in ovine fetal ovaries. J. Reprod. Fertil. 106, 329–335.
Localization of mRNA encoding c-kit during the initiation of folliculogenesis in ovine fetal ovaries.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XitFKnt70%3D&md5=dae794d443bd826e9195f4eeb0f5b08eCAS | 8699418PubMed |

Cognie, Y., Benoit, F., Poulin, N., Khatir, H., and Driancourt, M. A. (1998). Effect of follicle size and of the FecB Booroola gene on oocyte function in sheep. J. Reprod. Fertil. 112, 379–386.
Effect of follicle size and of the FecB Booroola gene on oocyte function in sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXktVent7g%3D&md5=c45b9d833ec1eecc0adb4073df8c94edCAS | 9640277PubMed |

de Bruin, J. P., Dorland, M., Spek, E. R., Posthuma, G., van Haaften, M., Looman, C. W., and te Velde, E. R. (2002). Ultrastructure of the resting ovarian follicle pool in healthy young women. Biol. Reprod. 66, 1151–1160.
Ultrastructure of the resting ovarian follicle pool in healthy young women.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XitlClu7o%3D&md5=a22f29dd5f88ed9360bcce1b0a578e88CAS | 11906936PubMed |

Devine, P. J., Payne, C. M., McCuskey, M. K., and Hoyer, P. B. (2000). Ultrastructural evaluation of oocytes during atresia in rat ovarian follicles. Biol. Reprod. 63, 1245–1252.
Ultrastructural evaluation of oocytes during atresia in rat ovarian follicles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXnslCls7w%3D&md5=8315ff97c965406fa324260c6043c16cCAS | 11058526PubMed |

Dong, J., Albertini, D. F., Nishimori, K., Kumar, T. R., Lu, N., and Matzuk, M. M. (1996). Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383, 531–535.
Growth differentiation factor-9 is required during early ovarian folliculogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28Xmt1GrsL0%3D&md5=07a2013be8b9aaa5b12b11f41fae05b5CAS | 8849725PubMed |

Dvorak, M. (1989). Ultrastructure and quantitative analysis of mouse and human oocytes. Prog. Clin. Biol. Res. 296, 273–280.
| 1:STN:280:DyaL1M3pslSiuw%3D%3D&md5=5076d68d86b64e915330c7f4afacc789CAS | 2740379PubMed |

Elias, H., Hennig, A., and Schwartz, D. E. (1971). Stereology: applications to biomedicalresearch. Physiol. Rev. 51, 158–200.
| 1:STN:280:DyaE3M%2FotVyhtg%3D%3D&md5=93840bd043738bfd6b08ccb80a11651cCAS | 4924033PubMed |

Elvin, J. A., Yan, C., Wang, P., Nishimori, K., and Matzuk, M. M. (1999). Molecular characterization of the follicle defects in the growth differentiation factor 9-deficient ovary. Mol. Endocrinol. 13, 1018–1034.
Molecular characterization of the follicle defects in the growth differentiation factor 9-deficient ovary.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXjs1yns7Y%3D&md5=1f0de6770f17a88b3b99c00dbb588e33CAS | 10379899PubMed |

Fair, T., Hulshof, S. C., Hyttel, P., Greve, T., and Boland, M. (1997). Oocyte ultrastructure in bovine primordial to early tertiary follicles. Anat. Embryol. 195, 327–336.
Oocyte ultrastructure in bovine primordial to early tertiary follicles.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2s3mtFOrtg%3D%3D&md5=ddabe33ac7aa6a4d79d3e7d0f891b7b2CAS | 9108198PubMed |

Feary, E. S., Juengel, J. L., Smith, P., French, M. C., O’Connell, A. R., Lawrence, S. B., Galloway, S. M., Davis, G. H., and McNatty, K. P. (2007). Patterns of expression of messenger RNAs encoding GDF9, BMP15, TGFBR1, BMPR1b, and BMPR2 during follicular development and characterization of ovarian follicular populations in ewes carrying the woodlands Fecx2w mutation. Biol. Reprod. 77, 990–998.
Patterns of expression of messenger RNAs encoding GDF9, BMP15, TGFBR1, BMPR1b, and BMPR2 during follicular development and characterization of ovarian follicular populations in ewes carrying the woodlands Fecx2w mutation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhsVSgtLbP&md5=0cba49467f5e08d10ccef6ee18ef35bcCAS | 17715428PubMed |

Frankenberg, S., and Selwood, L. (2001). Ultrastructure of oogenesis in the brushtail possum. Mol. Reprod. Dev. 58, 297–306.
Ultrastructure of oogenesis in the brushtail possum.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXhtVSiu7Y%3D&md5=46371ecd37bc1fdec9a7fa99e3fff264CAS | 11170271PubMed |

Galloway, S. M., McNatty, K. P., Cambridge, L. M., Laitinen, M. P. E., Juengel, J. L., Sakari, T., Robert, J., McLaren, J., Luiro, K., Dodds, K. G., Montgomery, G. W., Beattie, A. E., Davis, G. H., and Ritvos, O. (2000). Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat. Genet. 25, 279–283.
Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXkvFKltbs%3D&md5=9326bcd9237d2b181f1d11a104125965CAS | 10888873PubMed |

Gootwine, E., Rozov, A., Bor, A., and Reicher, S. (2006). Carrying the FecB (booroola) mutation is associated with lower birth weight and slower post-weaning growth rate for lambs, as well as a lighter mature bodyweight for ewes. Reprod. Fertil. Dev. 18, 433–437.
Carrying the FecB (booroola) mutation is associated with lower birth weight and slower post-weaning growth rate for lambs, as well as a lighter mature bodyweight for ewes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XjtV2hu78%3D&md5=708fd1def1bd91800ad809f3760294ddCAS | 16737636PubMed |

Hayat, M. A. (1981). ‘Fixation for Electron Microscopy.’ (Academic Press: New York.)

Hertig, A. T., and Adams, E. C. (1967). Studies on the human oocyte and its follicle. I. Ultrastructural and histochemical observations on the primordial follicle stage. J. Cell Biol. 34, 647–675.
Studies on the human oocyte and its follicle. I. Ultrastructural and histochemical observations on the primordial follicle stage.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaF2s3ht1Kisw%3D%3D&md5=69783fa057e7ae56d37894fc5b971814CAS | 4292010PubMed |

Ide, H., Katoh, M., Sasaki, H., Yoshida, T., Aoki, K., Nawa, Y., Osada, Y., Sugimura, T., and Terada, M. (1997). Cloning of human bone morphogenetic protein type IB receptor (BMP-IB) and its expression in prostate cancer in comparison with other BMPRs. Oncogene 14, 1377–1382.
Cloning of human bone morphogenetic protein type IB receptor (BMP-IB) and its expression in prostate cancer in comparison with other BMPRs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXit12jur4%3D&md5=e2f15377e36f939f6c2caa1e8f06e991CAS | 9178898PubMed |

Juengel, J. L., Reader, K. L., Bibby, A. H., Lun, S., Ross, I., Haydon, L. J., and McNatty, K. P. (2006). The role of bone morphogenetic proteins 2, 4, 6 and 7 during ovarian follicular development in sheep: contrast to rat. Reproduction 131, 501–513.
The role of bone morphogenetic proteins 2, 4, 6 and 7 during ovarian follicular development in sheep: contrast to rat.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xjs12jsLw%3D&md5=70ca25737d414b88736e2fc3e62b22f0CAS | 16514193PubMed |

Knight, P. G., and Glister, C. (2006). TGF-beta superfamily members and ovarian follicle development. Reproduction 132, 191–206.
TGF-beta superfamily members and ovarian follicle development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xpt1Wjsr0%3D&md5=e3952199251c52a7267a52410fc3d2c7CAS | 16885529PubMed |

Lundy, T., Smith, P., O’Connell, A., Hudson, N. L., and McNatty, K. P. (1999). Populations of granulosa cells in small follicles of the sheep ovary. J. Reprod. Fertil. 115, 251–262.
Populations of granulosa cells in small follicles of the sheep ovary.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXisFWkuro%3D&md5=26db52de84797b17d27e2e00bd3baf83CAS | 10434930PubMed |

McNatty, K. P., Smith, P., Hudson, N. L., Heath, D. A., Tisdall, D. J., O, W. S., and Braw-Tal, R. (1995). Development of the sheep ovary during fetal and early neonatal life and the effect of fecundity genes. J. Reprod. Fertil. Suppl. 49, 123–135.
| 1:STN:280:DyaK2MzkvV2qug%3D%3D&md5=30b7bafdeef68b0820e31e9b45ceda7aCAS | 7623307PubMed |

McNatty, K. P., Juengel, J. L., Wilson, T., Galloway, S. M., and Davis, G. H. (2001). Genetic mutations influencing ovulation rate in sheep. Reprod. Fertil. Dev. 13, 549–555.
Genetic mutations influencing ovulation rate in sheep.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD383lvFyrtQ%3D%3D&md5=68e04fd4adc876f188565a59486d9e4eCAS | 11999305PubMed |

McNatty, K. P., Galloway, S. M., Wilson, T., Smith, P., Hudson, N. L., O’Connell, A., Bibby, A. H., Heath, D. A., Davis, G. H., Hanrahan, J. P., and Juengel, J. L. (2005). Physiological effects of major genes affecting ovulation rate in sheep. Genet. Sel. Evol. 37, S25–S38.
Physiological effects of major genes affecting ovulation rate in sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXht1ens74%3D&md5=e3dae4e7a36134d419bbe1e2fdc7d631CAS | 15601593PubMed |

McNatty, K. P., Lawrence, S., Groome, N. P., Meerasahib, M. F., Hudson, N. L., Whiting, L., Heath, D. A., and Juengel, J. L. (2006). Oocyte signalling molecules and their effects on reproduction in ruminants. Reprod. Fertil. Dev. 18, 403–412.
Oocyte signalling molecules and their effects on reproduction in ruminants.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XjtV2hurY%3D&md5=b13600c34f45b9faa813867ed6f36083CAS | 16737633PubMed |

Moore, R. K., Otsuka, F., and Shimasaki, S. (2003). Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells. J. Biol. Chem. 278, 304–310.
Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XpvVWgtLc%3D&md5=2babed654b78fd42b7882165febc6e1cCAS | 12419820PubMed |

Motta, P. M., Makabe, S., Naguro, T., and Correr, S. (1994). Oocyte follicle cells association during development of human ovarian follicle. A study by high resolution scanning and transmission electron microscopy. Arch. Histol. Cytol. 57, 369–394.
Oocyte follicle cells association during development of human ovarian follicle. A study by high resolution scanning and transmission electron microscopy.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2M7os1ahsg%3D%3D&md5=f7f2d5600d7a560b5a81635caaeef6c3CAS | 7880591PubMed |

Mulsant, P. (2001). Mutation in bone morphogenetic protein receptor-Ib is associated with increased ovulation rate in booroola merino ewes. Proc. Natl Acad. Sci. USA 98, 5104–5109.
Mutation in bone morphogenetic protein receptor-Ib is associated with increased ovulation rate in booroola merino ewes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXjt1Ons74%3D&md5=0a41523a6b6ff652de247bdf276831b4CAS | 11320249PubMed |

Nicol, L., Bishop, S. C., Pong-Wong, R., Bendixen, C., Holm, L. E., Rhind, S. M., and McNeilly, A. S. (2009). Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in thoka sheep. Reproduction 138, 921–933.
Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in thoka sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsFKlur%2FP&md5=c70589fcfc0ae8b74b6fe8c8dd9dbb1dCAS | 19713444PubMed |

Parfenov, V. N., Davis, D. S., Pochukalina, G. N., Kostyuchek, D., and Murti, K. G. (2000). Nuclear distribution of RNA polymerase ii in human oocytes from antral follicles: dynamics relative to the transcriptional state and association with splicing factors. J. Cell. Biochem. 77, 654–665.
Nuclear distribution of RNA polymerase ii in human oocytes from antral follicles: dynamics relative to the transcriptional state and association with splicing factors.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXjsFersLY%3D&md5=801611420e0d34fd0fdd8213db3017e4CAS | 10771521PubMed |

Parrott, J. A., and Skinner, M. K. (1999). Kit-ligand/stem cell factor induces primordial follicle development and initiates folliculogenesis. Endocrinology 140, 4262–4271.
Kit-ligand/stem cell factor induces primordial follicle development and initiates folliculogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXlslSru7k%3D&md5=888a0f980e0ed7e87f381bee3ee69095CAS | 10465300PubMed |

Ross, M. H., Romrell, L. J., and Kaye, G. I. (Eds) (1995). ‘Histology. A Text and Atlas.’ 3rd edn. (Williams & Wilkins: Baltimore.)

Sawyer, H. R., Smith, P., Heath, D. A., Juengel, J. L., Wakefield, S. J., and McNatty, K. P. (2002). Formation of ovarian follicles during fetal development in sheep. Biol. Reprod. 66, 1134–1150.
Formation of ovarian follicles during fetal development in sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XitlClu70%3D&md5=7e01e86b5f5f26b8d91db3930d1e89b0CAS | 11906935PubMed |

Smith, P., Hudson, N. L., Shaw, L., Heath, D. A., Condell, L., Phillips, D. J., and McNatty, K. P. (1993). Effects of the Booroola gene (FecB) on body weight, ovarian development and hormone concentrations during fetal life. J. Reprod. Fertil. 98, 41–54.
Effects of the Booroola gene (FecB) on body weight, ovarian development and hormone concentrations during fetal life.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXltV2gs74%3D&md5=15b25316a7060082d79cbca940627f72CAS | 8345478PubMed |

Souza, C. J., MacDougall, C., Campbell, B. K., McNeilly, A. S., and Baird, D. T. (2001). The Booroola (FecB) phenotype is associated with a mutation in the bone morphogenetic receptor type 1 B (BMPR1B) gene. J. Endocrinol. 169, R1–R6.
The Booroola (FecB) phenotype is associated with a mutation in the bone morphogenetic receptor type 1 B (BMPR1B) gene.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXjsFarur8%3D&md5=622448128d64f129866a58bef63472e3CAS | 11312159PubMed |

Souza, C. J. H., Campbell, B. K., McNeilly, A. S., and Baird, D. T. (2002). Effect of bone morphogenetic protein 2 (BMP2) on oestradiol and inhibin a production by sheep granulosa cells, and localization of BMP receptors in the ovary by immunohistochemistry. Reproduction 123, 363–369.
Effect of bone morphogenetic protein 2 (BMP2) on oestradiol and inhibin a production by sheep granulosa cells, and localization of BMP receptors in the ovary by immunohistochemistry.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xit1Clsro%3D&md5=70337abff4e8ad0cda78bb12b67fe09dCAS |

Tassell, R., and Kennedy, J. P. (1980). Early follicular development and atretic changes in the ovary of the lamb: fine structure and histochemistry. Aust. J. Biol. Sci. 33, 675–687.
| 1:STN:280:DyaL3M3jt1SlsQ%3D%3D&md5=e540a963ffbd48e0e0d793c349eda749CAS | 7247870PubMed |

Tisdall, D. J., Quirke, L. D., Smith, P., and McNatty, K. P. (1997). Expression of the ovine stem cell factor gene during folliculogenesis in late fetal and adult ovaries. J. Mol. Endocrinol. 18, 127–135.
Expression of the ovine stem cell factor gene during folliculogenesis in late fetal and adult ovaries.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXivFWktr8%3D&md5=c271ef24963158b1373da2f687fbbd88CAS | 9134499PubMed |

Tisdall, D. J., Fidler, A. E., Smith, P., Quirke, L. D., Stent, V. C., Heath, D. A., and McNatty, K. P. (1999). Stem cell factor and c-kit gene expression and protein localization in the sheep ovary during fetal development. J. Reprod. Fertil. 116, 277–291.
Stem cell factor and c-kit gene expression and protein localization in the sheep ovary during fetal development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXkslOltLc%3D&md5=4071b95da09a96bd582a5868b93d21eaCAS | 10615253PubMed |

Wassarman, P. M., and Josefowicz, W. J. (1978). Oocyte development in the mouse: An ultrastructural comparison of oocytes isolated at various stages of growth and meiotic competence. J. Morphol. 156, 209–235.
Oocyte development in the mouse: An ultrastructural comparison of oocytes isolated at various stages of growth and meiotic competence.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE1c7ltlOktQ%3D%3D&md5=e1f0f4fc5343d5f84d7b863c1f55be19CAS | 642015PubMed |

Williams, M. (1977). ‘Quantitative Methods In Biology.’ (Elsevier/North-Holland Biomedical Press: Amsterdam.)

Wilson, T., Wu, X. Y., Juengel, J. L., Ross, I. K., Lumsden, J. M., Lord, E. A., Dodds, K. G., Walling, G. A., McEwan, J. C., O’Connell, A. R., McNatty, K. P., and Montgomery, G. W. (2001). Highly prolific booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells. Biol. Reprod. 64, 1225–1235.
Highly prolific booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXit1aqsr8%3D&md5=bc02defc484bc6ac557b11369fea952cCAS | 11259271PubMed |

Zamboni, L. (1974). Fine morphology of the follicle wall and follicle cell–oocyte association. Biol. Reprod. 10, 125–149.
Fine morphology of the follicle wall and follicle cell–oocyte association.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE2M7osVegtQ%3D%3D&md5=d0554ccd4e35249feadf9b83d21df0bcCAS | 4462822PubMed |