Journal of Assisted Reproduction and Genetics

, Volume 36, Issue 9, pp 1877–1890 | Cite as

Amyloid-like substance in mice and human oocytes and embryos

  • Ricardo N. Pimentel
  • Paula A. Navarro
  • Fang Wang
  • LeRoy G. RobinsonJr.
  • Michael Cammer
  • Fengxia Liang
  • Yael Kramer
  • David Lawrence. KeefeEmail author
Gamete Biology



To identify and characterize amyloid-like substance (ALS) in human and mouse oocytes and preimplantation embryos.


An experimental prospective pilot study. A total of 252 mouse oocytes and preimplantation embryos and 50 immature and in vitro matured human oocytes and parthenogenetic human embryos, from 11 consenting fertility patients, ages 18–45. Fluorescence intensity from immunofluorescent staining and data from confocal microscopy were quantified. Data were compared by one-way analysis of variance, with the least square-MEANS post-test, Pearson correlation coefficients (r), and bivariate analyses (t tests). ALS morphology was verified using transmission electron microscopy.


Immunostaining for ALS appears throughout the zona pellucida, as well as in the cytoplasm and nucleus of mouse and human oocytes, polar bodies, and parthenogenetic embryos, and mouse preimplantation embryos. In mouse, 2-cell embryos exhibited the highest level of ALS (69000187.4 ± 6733098.07). Electron microscopy confirmed the presence of ALS. In humans, fresh germinal vesicle stage oocytes exhibited the highest level of ALS (4164.74088 ± 1573.46) followed by metaphase I and II stages (p = 0.008). There was a significant negative association between levels of ALS and patient body mass index, number of days of ovarian stimulation, dose of gonadotropin used, time between retrieval and fixation, and time after the hCG trigger. Significantly higher levels of ALS were found in patients with AMH between 1 and 3 ng/ml compared to < 1 ng/ml.


We demonstrate for the first time the presence, distribution, and change in ALS throughout some stages of mouse and human oocyte maturation and embryonic development. We also determine associations between ALS in human oocytes with clinical characteristics.


Amyloid Oocyte quality Reproductive aging female fertility 



We thank NYULMC DART Microscopy Lab for their assistance: Alice Liang, Chris Petzold and K isten Dancel-Manning with TEM work, and Michael Cammer for LM work.

Compliance with ethical standards

Financial disclosure

Support from FAPESP, Brazil (Process 2015/21907-0) (PN) and the Stanley H. Kaplan Endowment Fund.

Supplementary material

10815_2019_1530_MOESM1_ESM.docx (14.4 mb)
ESM 1 (DOCX 14768 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Research Scientist from the Department of Obstetrics and GynecologyNew York University School of MedicineNew YorkUSA
  2. 2.Human Reproduction Division, Department of Obstetrics and Gynecology, Faculty of Medicine of Ribeirao PretoUniversity of Sao PauloRibeirao PretoBrazil
  3. 3.Department of Obstetrics and Gynecology, Langone Medical CenterNew York UniversityNew YorkUSA
  4. 4.DART Microscopy LaboratoryNew York University School of MedicineNew YorkUSA

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