Dados do Trabalho

Title

The role of in vitro gametogenesis from pluripotent stem cells in assisted human reproduction.

Objective

The objective was to analyze the role of in vitro gametogenesis (IVG) from the differentiation of pluripotent stem cells as a support tool for assisted human reproduction procedures.

Methods

An integrative literature review was carried out considering the last 5 years, from the following databases: National Library of Medicine National Institutes of Health of the USA (PubMed), Virtual Health Library (BVS), Latin American and Caribbean Literature/ Bibliographic Index Español en Ciencias de la Salud (Lilacs) and Medical Literature Analysis and Retrieval System Online (Medline).
Experimental and opinion articles were selected, only in English and with IVG as their central theme. From the analysis of the 17 articles selected, it was identified that much has been studied since the first report of success in obtaining in vitro gametes derived from mouse embryonic stem cells.

Results

This process was initially described in 2011 by Professor Katsuhiko Hayashi's group and was called in vitro gametogenesis (IVG). Gametes can be produced in vitro from two different cell types; they can be derived from induced pluripotent stem cells (iPSCs) or pluripotent stem cells (ESCs) derived from cloned embryos or embryos produced by IVF.
Regarding its clinical use, three broad applications of IVG can be distinguished: in heterosexual couples, homosexual couples, and individual reproduction. Specifically in the case of using iPSC, it would be possible to generate functional autologous gametes from the couple's somatic cells, eliminating the need to resort to a gamete or embryo bank.
It was also described that iPSCs use for IVG have limitations, there are findings that iPSCs retain residual epigenetic memory, typical of parental somatic cells, which can lead to a bias in their propensity to differentiate into different lineages. However, one of the main challenges of IVG is the reconstitution of the complex processes that involve gametogenesis, culminating in the production of a viable and functional sperm or oocyte. Also, before reaching the threshold of differentiation of iPSCs or primordial germ cells, it is necessary to be able to evolve in vitro growth and in vitro maturation of gametes. Furthermore, the development of gamete production in vitro brings with it, in addition to helping infertile couples, the possibility of genetic manipulation of these cells.
It would be possible to select cells free of genetic diseases, specific characteristics of the offspring, in addition to use in research such as analysis of the differentiation process of embryonic stem cells, X chromosome inactivation, fertilization, early embryonic development, germ cell tumors and gene editing (CRISPR/Cas9). This wide range of possibilities raised questions about the idea of applying regenerative and reproductive medicine to humans in practice and brought legal and ethical issues into focus.

Conclusion

IVG is a technique capable of reconstituting spermatogenesis or oogenesis in vitro from iPSCs, promoting their differentiation into viable gametes, which have the same genetic as the infertile patient. The gametes can be fertilized using IVF techniques and do not require the donation of gametes and embryos, making it possible to have a child with a genetic from both partners. It is a promising methodology that may be used as a tool in the treatment of infertility, particularly in cases of germ cell aplasia.
Therefore, the development of IVG may help in understanding not only gametogenesis, but also factors related to infertility and genetic diseases. Although it is a promising technique for both reproductive and regenerative medicine, many discussions have been held about the ethical aspects and social repercussions of this technique, such as the possibility of gene manipulation.

Keywords

Gametogenesis, Pluripotent Stem Cells, Fertilization.