Skip to main content

Advertisement

Log in

Optimization of estrogen dosage for uterine receptivity for implantation in post-coital bilaterally ovariectomized mice

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Estrogens and progesterone, in unison and/or separately, synchronize the distinct events of blastocyst development, uterine priming and receptivity induction for implantation. In contrast to high implantation failure rates, the mechanistic concepts regarding the uterine receptivity for implantation still remain elusive. The present study aims to define the minimum estradiol (E2) dose to induce uterine receptivity for successful implantation in post-coitus bilaterally ovariectomized (BLO) progesterone-primed uterus of mice. Post-coital sperm-positive adult female mice were divided into two groups. In both the groups, delayed implantation was induced by BLO on post-coitus Day 4 (D4). Group 1 received 2 mg of progesterone (P4) from D5 until sacrifice, and E2 injection of 3.0, 10.0, 25.0 and 50.0 ng on D7. On D8, all mice of this group were sacrificed except the mice that received second dose of 25.0 ng of E2 on D8 and were sacrificed on D9. Group 2 followed the same doses, but were given simultaneously on D4, and sacrificed on D5. The mice that received second doses of 25.0 ng E2 were sacrificed on D6. The minimum dose of E2 required to induce uterine receptivity for implantation is a single dose of 50.0 ng E2. The uterus remained refractory following short receptive period at E2 doses lower than 50.0 ng, which is just sufficient to establish desired uterine receptivity. However, repeated administration of sub-threshold doses of 25.0 ng of E2 could also not effectively sustain uterine receptivity towards successful implantation.

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.

Fig. 1
Fig. 2

Data availability

The raw data supporting the conclusion of this article will be made available by the authors, without undue reservation.

References

  1. Dorostghoal M, Hamid-o-allah Ghaffari FM, Keikhah N (2018) Overexpression of endometrial estrogen receptor-alpha in the window of implantation in women with unexplained infertility. Int J Fertil Steril 12:37–42

    CAS  Google Scholar 

  2. Fukui Y, Hirota Y, Matsuo M, Gebril M, Akaeda S, Hiraoka T, Osuga Y (2019) Uterine receptivity, embryo attachment, and embryo invasion: multistep processes in embryo implantation. Reprod Med Biol 18:234–240

    Article  CAS  Google Scholar 

  3. Mokashi-Bhalerao N (2018) Molecular Mechanisms: Endometrial Receptivity and Implantation. The Infertility Manual. 16.

  4. Li Y, Sun X, Dey SK (2015) Entosis allows timely elimination of the luminal epithelial barrier for embryo implantation. Cell Rep 11:358–65

    Article  CAS  Google Scholar 

  5. Bhattarai T, Datta S, Chaudhuri P, Bhattacharya Kand Sengupta P (2014) Effect of progesterone supplementation on post-coital unilaterally ovariectomized superovulated mice in relation to implantation and pregnancy. Asian J Pharm Clin Res 7:29–31

    Google Scholar 

  6. Huet-Hudson YM, Andrews GK, Dey SK (1989) Cell type-specific localization of c-myc protein in the mouse uterus: modulation by steroid hormones and analysis of the periimplantation period. Endocrinology 125:1683–1690

    Article  CAS  Google Scholar 

  7. Li Q, Kannan A, DeMayo FJ, Lydon JP, Cooke PS, Yamagishi H, Srivastava D, Bagchi MK, Bagchi IC (2011) The antiproliferative action of progesterone in uterine epithelium is mediated by Hand2. Science 331:912–6

    Article  CAS  Google Scholar 

  8. Matsumoto H, Fukui E, Yoshizawa M (2016) Molecular and cellular events involved in the completion of blastocyst implantation. Reprod Med Biol 15:53–58

    Article  CAS  Google Scholar 

  9. Dutta S, Sengupta P (2016) Men and mice: relating their ages. Life Sci 152:244–8

    Article  CAS  Google Scholar 

  10. Wang H, Dey SK (2006) Roadmap to embryo implantation: clues from mouse models. Nat Rev Genet 7:185–99

    Article  Google Scholar 

  11. Kelleher AM, Milano-Foster J, Behura SK, Spencer TE (2018) Uterine glands coordinate on-time embryo implantation and impact endometrial decidualization for pregnancy success. Nat Comm 9:1–2

    Article  CAS  Google Scholar 

  12. Young SL, Garneau A (2020) Endocrinology of Implantation. InMaternal-Fetal and Neonatal Endocrinology. Academic Press, Cambridge, pp 521–525

    Google Scholar 

  13. Robertshaw I, Bian F, Das SK (2016) Mechanisms of uterine estrogen signaling during early pregnancy in mice: an update. J Mol Endocrinol 56:R127-38

    Article  CAS  Google Scholar 

  14. Pawar S, Laws MJ, Bagchi IC, Bagchi MK (2015) Uterine epithelial estrogen receptor-alpha controls decidualization via a paracrine mechanism. Mol Endocrinol 29:1362–74

    Article  CAS  Google Scholar 

Download references

Acknowledgements

None

Funding

The authors have not disclosed any funding.

Author information

Authors and Affiliations

Authors

Contributions

KB, PS, SD and AKS designed and planned the research. KB, PS and SD wrote the article and made the final revisions. The last corrections and adjustments have been made by PS, SD and AKS. All authors have read and approved the manuscript.

Corresponding authors

Correspondence to Koushik Bhattacharya or Pallav Sengupta.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

The study proposal was approved by the Institutional Animal Ethical Committee (28/P/S/IAEC/2022).

Consent for Publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bhattacharya, K., Sengupta, P., Dutta, S. et al. Optimization of estrogen dosage for uterine receptivity for implantation in post-coital bilaterally ovariectomized mice. Mol Cell Biochem 478, 285–289 (2023). https://doi.org/10.1007/s11010-022-04505-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-022-04505-1

Keywords

Navigation