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• W2549227230 abstract "Societies evolve - perhaps not as directly or as quickly as some may wish, but they are constantly in flux. The parts of our communal structure that are based on reproductive differences between males and females, however, will always retain gender inequities, given the biological boundaries. Only women are capable of carrying a pregnancy and producing food for the infant in its early development, for instance. The narrower reproductive window for women relative to her male counterparts further magnifies these social distinctions between the sexes - wherein the term limit is due more to the finite number of eggs a female is born with than to the ability to carry a pregnancy to successful completion. Marked societal progress has been made to provide the balance needed for the reproductive and career development opportunities of parents, but few opportunities are available to delay the onset of pregnancy. Assisted reproductive technologies and cryopreservation of sperm and eggs have become an important option for men and women, especially for individuals confronting a health issue, such as cancer treatment or environmental exposure to toxicants. Although these options are not perfect, they do provide a means to manage reproductive potential to best suit life goals. Now imagine the ability to make eggs at almost any point in one's life, thereby extending one's reproductive window beyond the period of egg availability to the ability to successfully carry a fetus through pregnancy. Certainly the lifespan of the uterus or pregnancy is not limitless, but it is much longer than the period of egg production - to wit, altruistic grandmothers who provide surrogate pregnancies for others. Several years ago, the Saitou group reported an ability to generate cells capable of developing mostly in vitro into oocytes (Hayashi et al., 2012). They started with fibroblasts from mice, and through induced pluripotent stem cell technology created primordial germ cell like cells (PGCLCs) that were capable of making oocytes, but only if transferred back into the ovary of a female. This was a remarkable breakthrough in reproductive and regenerative technologies, but that last step requiring a functional ovary was limiting for translation of the technology to humans. But now that barrier has been overcome: the Hayashi and Saitou groups were able to make mouse oocytes completely in vitro - starting from a fibroblast of the female and ending with a proper, fertilizable egg (Hikabe et al., 2016). Wow! Shazam! Key to their success was mixing somatic cells from an embryonic day 12.5 mouse ovary with the developing PGCLCs to make a reconstituted ovary (rOvary). As in the intact organ, somatic cells are essential for oocyte development. Supplying appropriate media and hormonal stimulation resulted in predicted stage-specific oocyte development. Although the requirement for somatic ovarian cells with the PGCLCs presents a substantial limitation to the routine and complete control of the procedure, I do suspect that these and other investigators will learn how to derive the major somatic ovarian cells from the induced pluripotent stem cells pf the same female. The investigators point out that this version of the in vitro oocyte derivation procedure is not efficient. Although they made over 3,000 oocytes in 58 rOvaries, they also carefully document its shortcomings among many strains of mice, including lower quality of chromosome pairing in meiosis; a small level of contaminating oocytes from the somatic cells used to make rOvaries; an increase in aneuploidy; and some differences in the expression of genes. i These oocytes likely also experience increased stress from the prolonged culturing, as do most cells, which may compromise their reproductive potential. I would emphasize, though, that these shortcomings are also opportunities to teach us how the oocyte is made and regulated. While the production of oocytes is a remarkable feat, can these oocyte-like cells actually mature to a fertilizable egg that can give rise to pups? Yes. Although the rate of pups born from two-cell, rOvary-derived oocytes was only 3.5% (compared to over 60% of in vivo-derived oocytes), the pups that were born were healthy and, for the most part, normal in a variety of important metrics. The female pups derived from rOvary oocytes were even capable of forming blastocysts that could yield bona fide embryonic stem cell lines that contributed broadly among the tissue type& when introduced into host blastocysts. Thus, the developmental authenticity of the in vitro-derived oocytes is robust. Ok, so back to the issue of efficiency…. I do recall reading about the inefficiency of Henry Ford's production plant, of the Wright Brother's first plane, and of IBMs first “computer” - each of which were overcome with time and resources. I therefore fully suspect that efficiency of this procedure will improve as well as these historic engineering milestones. I also suspect that the translation of these techniques will rapidly move to primates, and then to humans. The next question, of course, is how society will deal with the success of this science. Gary M. Wessel" @default.
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• W2549227230 date "2016-11-01" @default.
• W2549227230 modified "2023-09-26" @default.
• W2549227230 title "Now that is a game changer: The entire reproductive cycle of an oocyte in a dish" @default.
• W2549227230 doi "https://doi.org/10.1002/mrd.22754" @default.
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