Disclosure

Gerald Phillip Schatten Pittsburgh Development Center Obstetrics, Gynecology & Reproductive Sciences Division of Developmental & Regenerative Medicine University of Pittsburgh School of Medicine Pittsburgh (PA), USA

Declared receipt of grants and contracts from the National Institute of Health How to Make Babies in the 21st Century?

Professor Gerald Schatten

USA Reproduction Still is Mysterious

1. Fertilization >> than Just Merging Two Nuclei, e.g. Mitochondria and Centrioles. 2. The Centrosome is Vital for Development and Defects Cause Cancers and Microcephaly. 3. Inheritance Involves Genetics and Epigenetics. 4. Manufactured Gametes May Accelerate Infertility Diagnostics and Contraceptives. 5. Neither the Ovary Nor the Testes is Fully Understood. 6. Aging, a Global Crisis, Affects Men and Women – Stem Cells May Help!

Congenital microcephaly

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Volume 166, Issue 2, pages 124-139, 9 MAY 2014 DOI: 10.1002/ajmg.c.31397 http://onlinelibrary.wiley.com/doi/10.1002/ajmg.c.31397/full#ajmgc31397-fig-0001 Congenital microcephaly

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Volume 166, Issue 2, pages 124-139, 9 MAY 2014 DOI: 10.1002/ajmg.c.31397 http://onlinelibrary.wiley.com/doi/10.1002/ajmg.c.31397/full#ajmgc31397-fig-0003 Congenital microcephaly

American Journal of Medical Genetics Part C: Seminars in Medical Genetics Volume 166, Issue 2, pages 124-139, 9 MAY 2014 DOI: 10.1002/ajmg.c.31397 http://onlinelibrary.wiley.com/doi/10.1002/ajmg.c.31397/full#ajmgc31397-fig-0004

Imaging Core Highlights Centrosome Structure

From: Anderhub, SJ, Kramer, A, and Maier, B. Cancer Letters 322(2012) 8-17 ارة AL QAMRA أو ، ان ن ان ن ام Alhazen ~965-1040 CE

Gerald Schatten Oregon Regional Primate Research Center and Oregon Health Sciences University Portland OR, USA

al-kimia اء

J. B. Gurdon et al., Science 322, 1811 -1815 (2008)

The eye according to Hunain ibn Ishaq. ~809-873 CE http://dx.doi.org/10.1016/j.stem.2013.01.009 Modeling Alzheimer’s Disease with iPSCs Reveals Stress Phenotypes Associated with Intracellular A and Differential Drug Responsiveness

Cell Stem Cell April 2013

Takayuki Kondo , Masashi Asai , Kayoko Tsukita , Yumiko Kutoku , Yutaka Ohsawa , Yoshihide Sunada , Keiko Imamura...

Cancer stem cells: are we missing the target? Jones et al. JNCI 96:583, 2004 Cancer Stem Cell Hypothesis Muḥammad ibn Mūsā al-Khwārizmī ~780-850 CE al-jabr ار ;earlier transliterated as Algoritmi Spermatogonial stem cell transplantation into Rhesus testes regenerates spermatogenesis producing functional sperm. Hermann, BSchatten, G, Mitalipov, S, Orwig, K. Cell Stem Cell NOT YET!

In 1873, Harvard Professor Edward H. Clarke wrote a well received book in which he claimed to have found the reason for “ female sterility ,” as infertility was then called.

The culprit, he said, was the education of women, which diverted energy from the reproductive machinery to the brain, resulting in women with “monstrous brains and puny bodies. ”

Cell Divisions for Sperm

15 yr= 35 20 = 150 30 = 380 40 = 610 50 = 840 SELFISH SPERMATOGONIAL SELECTION IN AGED HUMAN TESTES

Andrology 19 DEC 2013 DOI: 10.1111/j.2047-2927.2013.00175.x http://onlinelibrary.wiley.com/doi/10.1111/j.2047-2927.2013.00175.x/full#andr175-fig-0001 Nature. 2012 Aug 23;488(7412):471-5. doi: 10.1038/nature11396. Rate of de novo mutations and the importance of father's age to disease risk. Kong A , Frigge ML , Masson G , …Thorsteinsdottir U, Stefansson K . deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland. [email protected] Exodus 34:6–7

“God, merciful and gracious, slow to anger, and abounding in steadfast love and faithfulness, keeping steadfast love, forgiving iniquity and transgression and sin, but who will by no means clear the guilty, visiting the iniquity of the fathers on the children and the children’s children, to the third and the fourth generation .” .31:92 nr'aQ uelbNo ehT

send] w rrneuihb[otarry cye ly llwiruseht tuB , send sendgo an lht rrweiuihbt ed]r arhn[outb y of eodnite ohnatDe ebsyue lqyr ullswie hdant .tenvo ni ye dstue htt toaubawh oniectrruesR ا ر ںو وںو نا وارُ و وںون م ویر ا رو ور ر ناری ےر ط ں(دو ) اا ه وں ُط ن ںںؤ ا اوں ۔ و ں و هًو ں۔ EPICENTER OF EPIGENESIS The Scrotum Is Nuts Why are testicles kept in a vulnerable dangling sac? It’s not why you think.

Russian performance artist nails testicles to pavement to protest ‘police state’ apathy Pyotr Pavlensky, 29, sat naked with a nail piercing his scrotum outside Lenin's Mausoleum in broad daylight on Police Day.

Frontiers in Stem Cells &

IntensiveRegeneration hands-on training course

September 30October 6, 2016 MBL, Woods Hole, Massachusetts, USA

World class training featuring: • Current biological concepts & topics and related ethics and regulatory issues • Over 40 expert international faculty members • Newest lab technologies & equipment • Total immersion scientific inquiry

Competitive admissions deadline: July 2, 2016 More info at www.pdc.magee.edu Reproduction is Vital, Yet Complicated!

• Imprinted Genomes, Mitochondria, Centrosomes are yet to be fully understood. • The Centrosome is Vital for Development and Causes Cancer and Microcephaly. • Inheritance Involves Genetics and Epigenetics. • Manufactured Gametes May Accelerate Infertility Diagnostics and Contraceptives. • Neither the Ovary Nor the Testes is Fully Understood. • Aging, a Global Crisis, Affects Men and Women – Stem Cells May Help! Known Knowns vs Unknown Unknowns

There are things we know that we know.

There are known unknowns. That is to say there are things that we now know we don't know.

But there are also unknown unknowns. There are things we don't know we don't know.