Proteimics EndometrialProteimics Endometrial

(Francisco Dominguez Ph.D)

Currently, to evaluate the state of the endometrium of a woman there are a few techniques with little objective like the histological appraisal...

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Testicular stem cellsTesticular stem cells

(Carlos Simón MD, PhD)

Sperm generated in the adult male gonads from a small germinal stem cell population..

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Endometrial and myometrial stem cellsEndometrial and myometrial stem cells

 (Irene Cervelló Alcaraz, PhD)

The exceptional capacity of human endometrial tissue regeneration, that is renewed monthly and that can do it during all the life...

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Endometrial receptivityEndometrial receptivity

(Felipe Vilella, PhD)

The endometrium is the surface tissue that cover the walls of the uterus. In humans, this tissue suffers physiological and morphological modifications along the menstrual cycle...

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EndometriosisEndometriosis

(Francisco Domínguez PhD)

Endometriosis is one of the most frequent bening gynecological diseases in women, which may cause infertility.

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Ovarian hiperstimulationOvarian hiperstimulation

(Antonio Pellicer Martínez MD, PhD)

During assisted reproduction cycles and in order to obtain a higher number of oocytes women are administered Gonadotrophins....

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Embryonic viabilityEmbryonic viability

 (Francisco Dominguez, PhD)

Nowadays the unique method used to select the most viable embryo with the greatest potential in IVF implantation ...

 

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ReprogramingReprograming

 (José V. Medrano, PhD)

Infertility affects up to 15% of couples in reproductive age in Europe. Among the different diseases that can lead to infertility

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Vitamine D treatment on the uterine fibroids growthVitamine D treatment on the uterine fibroids growth

 Uterine fibroids are the most common benign tumor in women of reproductive age, affecting 25% of them...

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Endometrial DatabaseEndometrial Database

Universidad de Valencia

EDB is a service of Fundacion IVI, sponsored by University of Valencia (SPAIN)

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REPROGRAMING

Investigador
P.I. Responsible: Carlos Simón, MD, PhD.
Posdoctoral Investigator: Jose V. Medrano, PhD.
PhD Student: Ana M. Martínez
Lab. Technician: Alícia Quiñonero.


Reprogramación in vitro de células somáticas adultas humanas a células germinales

 

Infertility affects up to 15% of couples in reproductive age in Europe. Among the different diseases that can lead to infertility, poor gamete quality plays an important role and this is why there is an emerging demand on donated sperm and eggs in fertility clinics. The study of germ line development is necessary to understand poor gamete quality causes and design treatments to improve it. However, our current knowledge of this process in humans is little, mainly due to inaccessibility to early stages of development of human germ line development because of ethical impediments.
In this sense, the in vitro derivation of germ cells from adult somatic cells by genetic manipulation can lead to the establishment of an invaluable model for the study of the insights of human germ line development. Furthermore, knowledge obtained from this study can be a key to understand gamete-related diseases in order to improve their treatment. Finally, the development of non-integrative genetic manipulation techniques for the derivation of germ cells in vitro could convert them in clinical-grade gametes that allow patients to be the biological parents of their children without the need of donated gametes.
We based in previous reports from other groups that paved the way to achieve the correct transdifferentiation from on cell source to another different cell fate by genetic reprogramming. Thus, our goal is to achieve the successful in vitro reprogramming of human somatic cells to germ cells. These germ cells can be employed as an in vitro model to study the insights of hum germ line development, as well they can be used in the future as a source of gametes that allow patients with severe fertility impediments to generate functional gametes.

Figure 1. Schematic representation of the main events during mammalian germ line development.

   

Figure 2. Experimental design followed in this project.


Published Reports

1. Medrano JV, Pera RA, Simon C. Germ cell differentiation from pluripotent cells. Semin Reprod Med. 2013;31(1):14-23.


2. Medrano JV, Ramathal C, Nguyen HN, Simon C, Reijo Pera R. Divergent RNA-bindig proteins DAZL and VASA induce meiotic progression in human germ cells derived in vitro. Stem Cells. 2012; 30(3):441-51.


3. Panula S, Medrano JV, Kee K, Bergstrom R, Nguyen HN, Byers B, Wilson KD, Simon C, Hovatta O, Reijo Pera RA. Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells. Hum Mol Genet. 2011; 20(4):752-62


4. Medrano JV, Marqués-Marí AI, Aguilar CE, Riboldi M, Garrido N, Martínez-Romero A, Gil-Salom M, Simón C. Comparative analysis of the germ cell markers c-KIT, SSEA-1 and VASA in testicular biopsies from secretory versus obstructive azoospermia. Mol Hum Reprod. 2010; 16(11):811-17.


5. Aguilar C, Poo ME, Gomez E, Galan A, Sanchez E, Marques-Mari A, Ruiz V, Medrano J, Riboldi M, Enseñat-Waser R, Valbuena D, Simon C. Derivation, Characterization, Differentiation and Registration of Seven Human Embryonic Stem Cell Lines (VAL-3, -4, -5, -6M, -7, -8, and -9) on Human Feeder. In Vitro Cell Dev Biol Anim. 2009; 46(3-4):317-26.


6. Marques-Mari AI, Lacham-Kaplan O, Medrano JV, Simon C. Differentiation of Germ Cells and Gametes from Stem Cells. Hum Reprod Update. 2009; 1: 1–12.

Published book chapters

1. Medrano JV, Simon C, Reijo Pera R. Human germ cell differentiation from pluripotent embryonic stem cells and induced pluripotent stem cells. In Wassarman and Rosenwaks (ed.), Human fertility: Methods and protocols. Humana press. In press.


2. Medrano JV, Marqués-Marí AI, Simon C. Germline Differentiation From Stem Cells. In Sook-Cheng LIM (ed.), Stem cells: from bench to the bedside, 2nd edition. World Scientific publishing. 2010; 557-582.


3. Marques-Mari AI, Medrano JV, Simon C. Differentiating Gametes from Stem Cells. In H. Baharvand (ed.), Trends in Stem Cell Biology and Technology. Humana press. 2009; 137-147.