Ovarian germline stem cells
David F. Albertini, Ph.D.Southwest Embryology Summit,
January 4, 2016
Disclosure
• DA serves as a speaker for EMD Serono• DA served as SAB for OvaScience in 2012
Outline
• Background to the problem• Historical Considerations• The Data from 2004 to 2015• Matters of methodology and inconsistency arising
• The emergence of novel ARTs aimed at restoring female fertility
Background to the problem
• Rediscovery of the ovary as a “regenerative” organ
• Shift away from importance of somatic stem cells
• Embellishment of role of oocyte mitochondria in aging ……”mitomania” “fountain of youth”
• Confirmation that age‐related loss of oocyte quality is strictly a germ cell thing
Somatic or Oogonial Stem Cells (OSCs)
The oocyte‐follicle unit has many faces
Multiple Cell Communication pathways
McGinnis LK, Limback SD, Albertini DF (2013) Signaling modalities during oogenesis in mammals. In P M Wassarman, editor: Current Topics in Developmental Biology, Vol. 102,Academic Press, pp. 227-242. ISBN: 978-0-12-416024-8
76 genes And counting
What “maturation” means
• For the oocyte‐preparation for fertilization and embryo development
• For the follicle‐preparation for ovulation and formation of the corpus luteum
• For the ovary‐preparation for follicle selection and steroidogenesis for maintaining cyclicity
Maternal metabolic status impacts oocyte developmental competence
Conclusions
• The oocyte follicle unit is realized by multiple signaling mechanisms
• The metabolism of the follicle is geared to support the oocyte before steroid biosynthesis
• The acquisition and commitment to steroidogenic competence by the follicle launches the “cumulus” imperative to ensure competence of the oocyte.
Why we are having this conversation
Historical
• A very old problem has been misrepresented
• Resurfaces in the 1990s during the “APOPTOSIS” era…all things must die
• Stage is reset in 2004 Nature paper
The data then and now
• Yes there are stem cells somatic not germ line…and they are at the heart of ovarian cyclicity in organisms producing yolkless eggs
• And who cares…OvaScience likes to tout their treatments being banned by FDA…the martyr role suits their mentality
• And if you have money, you can buy treatment in how many countries now??? >5
Top Ten 2012 for Saito in mouse
The data from 2004‐2015
The Present‐2015
The Present‐2015
Digesting the latest work
1. Establishes problems with the isolation technique
2. Reinforces and extends a seemingly intractable problem with OSCs epitopes
3. Marshalls in the next wave of research that will possibly settle the question
Matters of methodology and inconsistency
Biomarkers and epitopes
CYTOPLASM
??????
CELL SURFACE
Detergent based dystopia
Oocyte‐like cells can be made from many tissues
And readily restore functionafter chemical sterilizationin mice
The emergence of novel ARTs aimed at restoring female fertility
• Several procedures have been used or are being developed that will treat infertility in females using OSCs
• Prospective adequately controlled clinical trials will not be conducted
• How many of your clinics are receiving queries about these treatments?
The real problem could be tractable and practical
Among the more objective discussions
Why we had this conversation
Conclusions
Journal Editors have exploited the topic for pressworthiness, not scientific rigor
The truth may never come out
Just hoping that we are not adding another “iatrogenic” influence of ARTs
On making a travesty of human ARTs
• Prophet of doom…in USA we live in a society that cannot differentiate between fact and fallacy
• Blind faith drives much of our conventional wisdom thru the eyes and mouths of snake oil dealers
• And this will unlikely change because greed runs law, medicine,