Stocktake Sale on now: wide range of books at up to 70% off!
Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

MRL/MpJ mice produce more oocytes and exhibit impaired fertilisation and accelerated luteinisation after superovulation treatment

Marina Hosotani https://orcid.org/0000-0003-0360-3360 A , Osamu Ichii A , Teppei Nakamura A B , Md Abdul Masum A , Yuki Otani A , Saori Otsuka-Kanazawa A , Yaser H. A. Elewa A C and Yasuhiro Kon A D
+ Author Affiliations
- Author Affiliations

A Laboratory of Anatomy, Division of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-Ku, Sapporo, Hokkaido 060-0818, Japan.

B Section of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories, Bunkyo 2–3, Chitose, Hokkaido 066-0052, Japan.

C Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt.

D Corresponding author. Email: y-kon@vetmed.hokudai.ac.jp

Reproduction, Fertility and Development 31(4) 760-773 https://doi.org/10.1071/RD18319
Submitted: 13 April 2018  Accepted: 9 November 2018   Published: 4 December 2018

Abstract

MRL/MpJ mice exhibit distinct phenotypes in several biological processes, including wound healing. Herein we report two unique phenotypes in the female reproductive system of MRL/MpJ mice that affect ovulation and luteinisation. We found that superovulation treatment resulted in the production of significantly more oocytes in MRL/MpJ than C57BL/6 mice (71.0 ± 13.4 vs 26.8 ± 2.8 respectively). However, no exon mutations were detected in genes coding for female reproductive hormones or their receptors in MRL/MpJ mice. In addition, the fertilisation rate was lower for ovulated oocytes from MRL/MpJ than C57BL/6 mice, with most of the fertilised oocytes showing abnormal morphology, characterised by deformation and cytolysis. Histological tracing of luteinisation showed that MRL/MpJ mice formed corpora lutea within 36 h after ovulation, whereas C57BL/6 mice were still at the corpora haemorrhagica formation stage after 36 h. The balance between the expression of matrix metalloproteinases and their tissue inhibitors shifted towards the former earlier after ovulation in MRL/MpJ than C57BL/6 mice. This result indicates a possible link between accelerated extracellular matrix remodelling in the ovulated or ruptured follicles and luteinisation in MRL/MpJ mice. Together, these findings reveal novel phenotypes in MRL/MpJ mice that provide novel insights into reproductive biology.

Additional keywords: extracellular matrix, histology, in vitro fertilisation, ovary.


References

Buhimschi, C. S., Zhao, G., Sora, N., Madri, J. A., Buhimschi, I. A., Allsworth, J., Stevens, E., Macones, G., Buhimschi, C., and Weiner, C. (2010). Myometrial wound healing post-cesarean delivery in the MRL/MpJ mouse model of uterine scarring. Am. J. Pathol. 177, 197–207.
Myometrial wound healing post-cesarean delivery in the MRL/MpJ mouse model of uterine scarring.Crossref | GoogleScholarGoogle Scholar |

Carpintero, N. L., Suárez, O. A., Mangas, C. C., Varea, C. G., and Rioja, R. G. (2014). Follicular steroid hormones as markers of oocyte quality and oocyte development potential. J. Hum. Reprod. Sci. 7, 187–193.
Follicular steroid hormones as markers of oocyte quality and oocyte development potential.Crossref | GoogleScholarGoogle Scholar |

Clark, L. D., Clark, R. K., and Heber-Katz, E. (1998). A new murine model for mammalian wound repair and regeneration. Clin. Immunol. Immunopathol. 88, 35–45.
A new murine model for mammalian wound repair and regeneration.Crossref | GoogleScholarGoogle Scholar |

Davis, J. S., and Rueda, B. R. (2002). The corpus luteum: an ovarian structure with maternal instincts and suicidal tendencies. Front. Biosci. 7, 1949–1978.
The corpus luteum: an ovarian structure with maternal instincts and suicidal tendencies.Crossref | GoogleScholarGoogle Scholar |

Ebner, T., Shebl, O., Moser, M., Sommergruber, M., and Tews, G. (2008). Developmental fate of ovoid oocytes. Hum. Reprod. 23, 62–66.
Developmental fate of ovoid oocytes.Crossref | GoogleScholarGoogle Scholar |

Gourevitch, D., Clark, L., Chen, P., Seitz, A., Samulewicz, S. J., and Heber-Katz, E. (2003). Matrix metalloproteinase activity correlates with blastema formation in the regenerating MRL mouse ear hole model. Dev. Dyn. 226, 377–387.
Matrix metalloproteinase activity correlates with blastema formation in the regenerating MRL mouse ear hole model.Crossref | GoogleScholarGoogle Scholar |

Heydemann, A. (2012). The super super-healing MRL mouse strain. Front. Biol. (Beijing) 7, 522–538.
The super super-healing MRL mouse strain.Crossref | GoogleScholarGoogle Scholar |

Hosotani, M., Ichii, O., Nakamura, T., Kanazawa, S. O., Elewa, Y. H. A., and Kon, Y. (2018). Autoimmune abnormality affects ovulation and oocyte-pick-up in MRL/MpJ-Faslpr/lpr mice. Lupus 27, 82–94.
Autoimmune abnormality affects ovulation and oocyte-pick-up in MRL/MpJ-Faslpr/lpr mice.Crossref | GoogleScholarGoogle Scholar |

Ichii, O., Konno, A., Sasaki, N., Endoh, D., Hashimoto, Y., and Kon, Y. (2008). Autoimmune glomerulonephritis induced in congenic mouse strain carrying telomeric region of chromosome 1 derived from MRL/MpJ. Histol. Histopathol. 23, 411–422.
Autoimmune glomerulonephritis induced in congenic mouse strain carrying telomeric region of chromosome 1 derived from MRL/MpJ.Crossref | GoogleScholarGoogle Scholar |

Kaufman, M. H., and Whittingham, D. G. (1972). Viability of mouse oocytes ovulated within 14 hours of an injection of pregnant mares’ serum gonadotrophin. J. Reprod. Fertil. 28, 465–468.
Viability of mouse oocytes ovulated within 14 hours of an injection of pregnant mares’ serum gonadotrophin.Crossref | GoogleScholarGoogle Scholar |

Kon, Y., and Endoh, D. (2000). Morphological study of metaphase-specific apoptosis in MRL mouse testis. Anat. Histol. Embryol. 29, 313–319.
Morphological study of metaphase-specific apoptosis in MRL mouse testis.Crossref | GoogleScholarGoogle Scholar |

Kon, Y., Konno, A., Hashimoto, Y., and Endoh, D. (2007). Ovarian cysts in MRL/MpJ mice originate from rete ovarii. Anat. Histol. Embryol. 36, 172–178.
Ovarian cysts in MRL/MpJ mice originate from rete ovarii.Crossref | GoogleScholarGoogle Scholar |

Lee, S.-H., Ichii, O., Otsuka, S., Yaser Hosney, E., Namiki, Y., Hashimoto, Y., and Kon, Y. (2011). Ovarian cysts in MRL/MpJ mice are derived from the extraovarian rete: a developmental study. J. Anat. 219, 743–755.
Ovarian cysts in MRL/MpJ mice are derived from the extraovarian rete: a developmental study.Crossref | GoogleScholarGoogle Scholar |

Leferovich, J. M., Bedelbaeva, K., Samulewicz, S., Zhang, X. M., Zwas, D., Lankford, E. B., and Heber-Katz, E. (2001). Heart regeneration in adult MRL mice. Proc. Natl Acad. Sci. USA 98, 9830–9835.
Heart regeneration in adult MRL mice.Crossref | GoogleScholarGoogle Scholar |

Li, X., Gu, W., Masinde, G., Hamilton-Ulland, M., Xu, S., Mohan, S., and Baylink, D. J. (2001). Genetic control of the rate of wound healing in mice. Heredity 86, 668–674.
Genetic control of the rate of wound healing in mice.Crossref | GoogleScholarGoogle Scholar |

Mermillod, P., Dalbis-Tran, R., Uzbekova, S., Thlie, A., Traverso, J.-M., Perreau, C., Papillier, P., and Monget, P. (2008). Factors affecting oocyte quality: who is driving the follicle? Reprod. Domest. Anim. 43, 393–400.
Factors affecting oocyte quality: who is driving the follicle?Crossref | GoogleScholarGoogle Scholar |

Nakamura, T., Sakata, Y., Otsuka-Kanazawa, S., Ichii, O., Chihara, M., Nagasaki, K., Namiki, Y., and Kon, Y. (2014). Genomic analysis of the appearance of ovarian mast cells in neonatal MRL/MpJ mice. PLoS One 9, e100617.
Genomic analysis of the appearance of ovarian mast cells in neonatal MRL/MpJ mice.Crossref | GoogleScholarGoogle Scholar |

Otsuka, S., Konno, A., Hashimoto, Y., Sasaki, N., Endoh, D., and Kon, Y. (2008). Oocytes in newborn MRL mouse testes. Biol. Reprod. 79, 9–16.
Oocytes in newborn MRL mouse testes.Crossref | GoogleScholarGoogle Scholar |

Practice Committee of the American Society for Reproductive Medicine, Birmingham, Alabama (2008). Gonadotropin preparations: past, present, and future perspectives. Fertil. Steril. 90, S13–S20.
Gonadotropin preparations: past, present, and future perspectives.Crossref | GoogleScholarGoogle Scholar |

Rashidi, Z., Azadbakht, M., Amini, A., and Karimi, I. (2014). Hydrostatic pressure affects in vitro maturation of oocytes and follicles and increases granulosa cell death. Cell J. 15, 282–293.

Revelli, A., Delle Piane, L., Casano, S., Molinari, E., Massobrio, M., and Rinaudo, P. (2009). Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics. Reprod. Biol. Endocrinol. 7, 40.
Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics.Crossref | GoogleScholarGoogle Scholar |

Santiago-Raber, M.-L., Laporte, C., Reininger, L., and Izui, S. (2004). Genetic basis of murine lupus. Autoimmun. Rev. 3, 33–39.
Genetic basis of murine lupus.Crossref | GoogleScholarGoogle Scholar |

Shiozuru, D., Ichii, O., Kimura, J., Nakamura, T., Elewa, Y. H. A., Otsuka-Kanazawa, S., and Kon, Y. (2016). MRL/MpJ mice show unique pathological features after experimental kidney injury. Histol. Histopathol. 31, 189–204.

Sirotkin, A. V. (2010). Effect of two types of stress (heat shock/high temperature and malnutrition/serum deprivation) on porcine ovarian cell functions and their response to hormones. J. Exp. Biol. 213, 2125–2130.
Effect of two types of stress (heat shock/high temperature and malnutrition/serum deprivation) on porcine ovarian cell functions and their response to hormones.Crossref | GoogleScholarGoogle Scholar |

Smith, M. F., McIntush, E. W., Ricke, W. A., Kojima, F. N., and Smith, G. W. (1999). Regulation of ovarian extracellular matrix remodelling by metalloproteinases and their tissue inhibitors: effects on follicular development, ovulation and luteal function. J. Reprod. Fertil. Suppl. 54, 367–381.

Spearow, J. L. (1988). Major genes control hormone-induced ovulation rate in mice. J. Reprod. Fertil. 82, 787–797.
Major genes control hormone-induced ovulation rate in mice.Crossref | GoogleScholarGoogle Scholar |

Stocco, C., Telleria, C., and Gibori, G. (2007). The molecular control of corpus luteum formation, function, and regression. Endocr. Rev. 28, 117–149.
The molecular control of corpus luteum formation, function, and regression.Crossref | GoogleScholarGoogle Scholar |

Takeo, T., and Nakagata, N. (2010). Combination medium of cryoprotective agents containing l-glutamine and methyl-β-cyclodextrin in a preincubation medium yields a high fertilization rate for cryopreserved C57BL/6J mouse sperm. Lab. Anim. 44, 132–137.
Combination medium of cryoprotective agents containing l-glutamine and methyl-β-cyclodextrin in a preincubation medium yields a high fertilization rate for cryopreserved C57BL/6J mouse sperm.Crossref | GoogleScholarGoogle Scholar |

Takeo, T., and Nakagata, N. (2011). Reduced glutathione enhances fertility of frozen/thawed C57BL/6 mouse sperm after exposure to methyl-beta-cyclodextrin. Biol. Reprod. 85, 1066–1072.
Reduced glutathione enhances fertility of frozen/thawed C57BL/6 mouse sperm after exposure to methyl-beta-cyclodextrin.Crossref | GoogleScholarGoogle Scholar |

Takeo, T., Hoshii, T., Kondo, Y., Toyodome, H., Arima, H., Yamamura, K., Irie, T., and Nakagata, N. (2008). Methyl-beta-cyclodextrin improves fertilizing ability of C57BL/6 mouse sperm after freezing and thawing by facilitating cholesterol efflux from the cells. Biol. Reprod. 78, 546–551.
Methyl-beta-cyclodextrin improves fertilizing ability of C57BL/6 mouse sperm after freezing and thawing by facilitating cholesterol efflux from the cells.Crossref | GoogleScholarGoogle Scholar |

Woessner, J. F. (1991). Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J. 5, 2145–2154.
Matrix metalloproteinases and their inhibitors in connective tissue remodeling.Crossref | GoogleScholarGoogle Scholar |

Yamashita, Y., Nakamura, T., Otsuka-Kanazawa, S., Ichii, O., and Kon, Y. (2015). Morphological characteristics observed during early follicular development in perinatal MRL/MpJ mice. Jpn. J. Vet. Res. 63, 25–36.
Morphological characteristics observed during early follicular development in perinatal MRL/MpJ mice.Crossref | GoogleScholarGoogle Scholar |

Yokoyama, M., and Hioki, K. (1990). The copulation rate and the embryo recovery rate following induced superovulation in various strains of mice. J. Mamm. Ova Res. 7, 89–94.
The copulation rate and the embryo recovery rate following induced superovulation in various strains of mice.Crossref | GoogleScholarGoogle Scholar |