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

Prospective evaluation of uterine receptivity in mice

Hitomi Nakamura A C , Takayoshi Hosono B , Keiichi Kumasawa A and Tadashi Kimura A
+ Author Affiliations
- Author Affiliations

A Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.

B Graduate School of Biomedical Engineering, Osaka Electro-Communication University, 1130-70 Kiyotaki, Shijyo-nawate, Osaka 5750063, Japan.

C Corresponding author. Email: hitomi@gyne.med.osaka-u.ac.jp

Reproduction, Fertility and Development 30(4) 619-623 https://doi.org/10.1071/RD17209
Submitted: 21 June 2017  Accepted: 29 August 2017   Published: 25 September 2017

Abstract

In current infertility treatments it is necessary to evaluate uterine receptivity in each menstrual cycle. During the implantation period, the uterus goes through many complex orchestrated changes, including changes to the glycocalyx. The changes to the glycocalyx are due to sialylation, sulfation and fucosylation. Can the measurement of in-vivo uterine pH and/or oxidation-reduction potential (ORP) determine the alterations of uterine endometrium for implantation and evaluate prospective uterine receptivity? In the present study we assessed in vivo uterine pH and ORP during the early stages of pregnancy in naïve mice, as well as in a murine model of implantation failure created by local and transient suppression of signal transducer and activator of transcription 3. There was no change in the in vivo uterine pH between post-coitus Days 2 and 6. In vivo uterine ORP was significantly higher compared to the day before. One day before implantation began, uterine ORP was significantly decreased in the implantation failure group compared with the naïve and control groups. Receiver operator characteristic (ROC) curve analysis of uterine ORP as a predictor of non-conception showed an area under the ROC curve of 0.96 (95% confidence interval 0.92–1.00). Thus, in vivo uterine ORP could be a parameter to prospectively evaluate uterine receptivity.

Additional keywords: implantation, infertility, in-vivo uterine oxidation-reduction potential (ORP).


References

Anderson, T. L., Olson, G. E., and Hoffman, L. H. (1986). Stage-specific alterations in the apical membrane glycoproteins of endometrial epithelial cells related to implantation in rabbits. Biol. Reprod. 34, 701–720.
Stage-specific alterations in the apical membrane glycoproteins of endometrial epithelial cells related to implantation in rabbits.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL28XktVCgs78%3D&md5=f4b45541f0c8f27ee6125366003ac52bCAS |

Aplin, J. D., Meseguer, M., Simon, C., Ortiz, M. E., Croxatto, H., and Jones, C. J. (2001). MUC1, glycans and the cell-surface barrier to embryo implantation. Biochem. Soc. Trans. 29, 153–156.
MUC1, glycans and the cell-surface barrier to embryo implantation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXkslentLY%3D&md5=4d16961ba93bf3c6bd85cacdf33ba3ccCAS |

Bell, S. C., Patel, S. R., Kirwan, P. H., and Drife, J. O. (1986). Protein synthesis and secretion by the human endometrium during the menstrual cycle and the effect of progesterone in vitro. J. Reprod. Fertil. 77, 221–231.
Protein synthesis and secretion by the human endometrium during the menstrual cycle and the effect of progesterone in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL28XktFyrs7g%3D&md5=b635d141990e2c4fbf1af60b444c0c9fCAS |

Boivin, J., Bunting, L., Collins, J. A., and Nygren, K. G. (2007). International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum. Reprod. 22, 1506–1512.
International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care.Crossref | GoogleScholarGoogle Scholar |

Cha, J., Sun, X., and Dey, S. K. (2012). Mechanisms of implantation: strategies for successful pregnancy. Nat. Med. 18, 1754–1767.
Mechanisms of implantation: strategies for successful pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xhslymsb3M&md5=c0a0894021ee678c54906cd54a6b5dfbCAS |

Conroy, C. W., Tyma, P., Daum, P. H., and Erman, J. E. (1978). Oxidation–reduction potential measurements of cytochrome c peroxidase and pH dependent spectral transitions in the ferrous enzyme. Biochim. Biophys. Acta 537, 62–69.
Oxidation–reduction potential measurements of cytochrome c peroxidase and pH dependent spectral transitions in the ferrous enzyme.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE1MXltVKjsA%3D%3D&md5=198e51c3918fbd442e672c83d8a01e4fCAS |

Díaz-Gimeno, P., Horcajadas, J. A., Martínez-Conejero, J. A., Esteban, F. J., Alamá, P., Pellicer, A., and Simón, C. (2011). A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature. Fertil. Steril. 95, 50–60.e15.
A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature.Crossref | GoogleScholarGoogle Scholar |

Fazleabas, A. T., and Kim, J. J. (2003). Development. What makes an embryo stick? Science 299, 355–356.
Development. What makes an embryo stick?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXhtlCit7Y%3D&md5=9ab1d5a82f09ce3da4cf9321298fc016CAS |

Genbacev, O. D., Prakobphol, A., Foulk, R. A., Krtolica, A. R., Ilic, D., Singer, M. S., Yang, Z. Q., Kiessling, L. L., Rosen, S. D., and Fisher, S. J. (2003). Trophoblast L-selectin-mediated adhesion at the maternal-fetal interface. Science 299, 405–408.
Trophoblast L-selectin-mediated adhesion at the maternal-fetal interface.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXjsF2rtg%3D%3D&md5=2ea31c8f4278f223ff5cb888ba28bc15CAS |

Hewitt, K., Beer, A. E., and Grinnell, F. (1979). Disappearance of anionic sites from the surface of the rat endometrial epithelium at the time of blastocyst implantation. Biol. Reprod. 21, 691–707.
Disappearance of anionic sites from the surface of the rat endometrial epithelium at the time of blastocyst implantation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL3cXjvVGktg%3D%3D&md5=2117c3faa3af661a6a6381f46f76f81dCAS |

Hey, N. A., Graham, R. A., Seif, M. W., and Aplin, J. D. (1994). The polymorphic epithelial mucin MUC1 in human endometrium is regulated with maximal expression in the implantation phase. J. Clin. Endocrinol. Metab. 78, 337–342.
| 1:CAS:528:DyaK2cXitFeksr8%3D&md5=85d3cce0a866a0772ee37256844285aeCAS |

Hoffman, L. H., Olson, G. E., Carson, D. D., and Chilton, B. S. (1998). Progesterone and implanting blastocysts regulate Muc1 expression in rabbit uterine epithelium. Endocrinology 139, 266–271.
Progesterone and implanting blastocysts regulate Muc1 expression in rabbit uterine epithelium.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXhtFOrug%3D%3D&md5=8c548bc7576a6299ad63fe9340d21dbcCAS |

Koot, Y. E., Teklenburg, G., Salker, M. S., Brosens, J. J., and Macklon, N. S. (2012). Molecular aspects of implantation failure. Biochim. Biophys. Acta 1822, 1943–1950.
Molecular aspects of implantation failure.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XptFahu7w%3D&md5=474e09f08dbf738d2f276a8325ec032dCAS |

Kubushiro, K., Kojima, K., Mikami, M., Nozawa, S., Iizuka, R., Iwamori, M., and Nagai, Y. (1989). Menstrual cycle-associated alteration of sulfogalactosylceramide in human uterine endometrium: possible induction of glycolipid sulfation by sex steroid hormones. Arch. Biochem. Biophys. 268, 129–136.
Menstrual cycle-associated alteration of sulfogalactosylceramide in human uterine endometrium: possible induction of glycolipid sulfation by sex steroid hormones.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1MXltFCqtw%3D%3D&md5=f05851e06946dab8d6bfa13d51ca2b33CAS |

McCormack, J. T., and Greenwald, G. S. (1974). Evidence for a preimplantation rise in oestradiol-17beta levels on day 4 of pregnancy in the mouse. J. Reprod. Fertil. 41, 297–301.
Evidence for a preimplantation rise in oestradiol-17beta levels on day 4 of pregnancy in the mouse.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE2MXotl2jsA%3D%3D&md5=486674dadabcc6608f2c6a9b600e5bd3CAS |

Morris, J. E., and Potter, S. W. (1984). A comparison of developmental changes in surface charge in mouse blastocysts and uterine epithelium using DEAE beads and dextran sulfate in vitro. Dev. Biol. 103, 190–199.
A comparison of developmental changes in surface charge in mouse blastocysts and uterine epithelium using DEAE beads and dextran sulfate in vitro.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2c7otlehtQ%3D%3D&md5=e00a480f154ebf1263f7790fce8984b1CAS |

Morris, J. E., Potter, S. W., and Gaza-Bulseco, G. (1988). Estradiol-stimulated turnover of heparan sulfate proteoglycan in mouse uterine epithelium. J. Biol. Chem. 263, 4712–4718.
| 1:CAS:528:DyaL1cXhs1Wks7k%3D&md5=e435a45b5f3a6236c56b0b1c031137b2CAS |

Nakamura, H., Kimura, T., Ikegami, H., Ogita, K., Koyama, S., Shimoya, K., Tsujie, T., Koyama, M., Kaneda, Y., and Murata, Y. (2003). Highly efficient and minimally invasive in-vivo gene transfer to the mouse uterus using haemagglutinating virus of Japan (HVJ) envelope vector. Mol. Hum. Reprod. 9, 603–609.
Highly efficient and minimally invasive in-vivo gene transfer to the mouse uterus using haemagglutinating virus of Japan (HVJ) envelope vector.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXnt1Kju7g%3D&md5=cce9a6d39ba62ea1c48d301892fa78a3CAS |

Nakamura, H., Kimura, T., Koyama, S., Ogita, K., Tsutsui, T., Shimoya, K., Taniguchi, T., Koyama, M., Kaneda, Y., and Murata, Y. (2006). Mouse model of human infertility: transient and local inhibition of endometrial STAT-3 activation results in implantation failure. FEBS Lett. 580, 2717–2722.
Mouse model of human infertility: transient and local inhibition of endometrial STAT-3 activation results in implantation failure.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XksFaqs7o%3D&md5=ee3891f2d677892e1123490a19664f55CAS |

Nakamura, H., Hosono, T., Minato, K., Hamasaki, T., Kumasawa, K., and Kimura, T. (2014). Importance of optimal local uterine blood flow for implantation. J. Obstet. Gynaecol. Res. 40, 1668–1673.
Importance of optimal local uterine blood flow for implantation.Crossref | GoogleScholarGoogle Scholar |

Quaas, A. M., and Hansen, K. R. (2016). The role of steroid hormone supplementation in non-assisted reproductive technology treatments for unexplained infertility. Fertil. Steril. 106, 1600–1607.
The role of steroid hormone supplementation in non-assisted reproductive technology treatments for unexplained infertility.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC28XhslCrs7vK&md5=3f7babd3e32e067cf1575141e5d2de5dCAS |

Ren, Q., Guan, S., Fu, J., and Wang, A. (2010). Temporal and spatial expression of Muc1 during implantation in sows. Int. J. Mol. Sci. 11, 2322–2335.
Temporal and spatial expression of Muc1 during implantation in sows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXntVGqtLc%3D&md5=eb498af89655def27d134eb56c1a33c5CAS |

Surveyor, G. A., Gendler, S. J., Pemberton, L., Das, S. K., Chakraborty, I., Julian, J., Pimental, R. A., Wegner, C. C., Dey, S. K., and Carson, D. D. (1995). Expression and steroid hormonal control of Muc-1 in the mouse uterus. Endocrinology 136, 3639–3647.
Expression and steroid hormonal control of Muc-1 in the mouse uterus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXntFKntbg%3D&md5=ccacc72bf5d9e9e760439818b93107b0CAS |

Wang, H., and Dey, S. K. (2006). Roadmap to embryo implantation: clues from mouse models. Nat. Rev. Genet. 7, 185–199.
Roadmap to embryo implantation: clues from mouse models.Crossref | GoogleScholarGoogle Scholar |

Zhu, Z., Deng, H., Fenderson, B. A., Nudelman, E. D., and Tsui, Z. (1990). Glycosphingolipids of human myometrium and endometrium and their changes during the menstrual cycle, pregnancy and ageing. J. Reprod. Fertil. 88, 71–79.
Glycosphingolipids of human myometrium and endometrium and their changes during the menstrual cycle, pregnancy and ageing.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXhsFGrt7Y%3D&md5=575c11806f6f24a63c0e3c71a419db6aCAS |

Zhu, Z., Cheng, L., Tsui, Z., Hakomori, S., and Fenderson, B. A. (1992). Glycosphingolipids of rabbit endometrium and their changes during pregnancy. J. Reprod. Fertil. 95, 813–823.
Glycosphingolipids of rabbit endometrium and their changes during pregnancy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38XmsV2isrc%3D&md5=59d6d13132db87ef48b41ee5a1e82d8eCAS |