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{"title"=>"Oocyte family trees: Old branches or new stems?", "type"=>"journal", "authors"=>[{"first_name"=>"Dori C.", "last_name"=>"Woods", "scopus_author_id"=>"8086207600"}, {"first_name"=>"Evelyn E.", "last_name"=>"Telfer", "scopus_author_id"=>"7004120379"}, {"first_name"=>"Jonathan L.", "last_name"=>"Tilly", "scopus_author_id"=>"7006078325"}], "year"=>2012, "source"=>"PLoS Genetics", "identifiers"=>{"scopus"=>"2-s2.0-84864634106", "doi"=>"10.1371/journal.pgen.1002848", "sgr"=>"84864634106", "isbn"=>"1553-7390", "pmid"=>"22844256", "issn"=>"15537390", "pui"=>"365384825"}, "id"=>"9d8c75f4-722d-3713-a86f-e6ec8a0a5e36", "link"=>"http://www.mendeley.com/research/oocyte-family-trees-old-branches-new-stems", "reader_count"=>43, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>17, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>7, "Student > Master"=>5, "Other"=>3, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>17, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>7, "Student > Master"=>5, "Other"=>3, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>10, "Agricultural and Biological Sciences"=>27, "Arts and Humanities"=>1, "Veterinary Science and Veterinary Medicine"=>1, "Psychology"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>27}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Arts and Humanities"=>{"Arts and Humanities"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"United States"=>3, "Brazil"=>1, "United Kingdom"=>1}, "group_count"=>2}

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• http://doi.org/10.1016/j.fertnstert.2018.12.015
• http://doi.org/10.1016/j.fertnstert.2013.06.036
• http://doi.org/10.3109/14647273.2015.1006692
• http://doi.org/10.1038/nm0912-1311
• http://doi.org/10.1530/REP-13-0181
• http://doi.org/10.1177/1179558119848007
• http://doi.org/10.3390/cells8020093
• http://doi.org/10.1038/nprot.2013.047
• http://doi.org/10.1186/scrt487
• http://doi.org/10.1177/1933719112462632
• http://doi.org/10.1016/j.maturitas.2013.04.017
• http://doi.org/10.3390/cells8080852
• http://doi.org/10.1016/j.maturitas.2015.07.017
• http://doi.org/10.1093/molehr/gaw015
• http://doi.org/10.1016/j.gde.2016.07.008
• http://doi.org/10.1186/s13039-016-0224-1
• http://doi.org/10.1177/1179558119870163
• http://doi.org/10.1530/JOE-14-0469
• http://doi.org/10.1186/s13048-016-0274-3

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• {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosgenetics%2Farticle%3Fid%3D10.1371%252Fjournal.pgen.1002848", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

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• {"type"=>"COMMENT", "annotationUri"=>"info:doi/10.1371/annotation/69c63d31-d35d-4042-889e-aac92e001a4d", "title"=>"Postnatal oocyte stem cells", "body"=>"The perspective seems to suggest that unilateral oophorectomy is not detrimental to the ovarian reserve. A number of human epidemiologic studies show that unilateral oophorectomy is associated with premature ovarian failure. \n\nThe authors of this perspective should also cite a recent article in PNAS by Kui and colleagues that pretty much proves that there are NO postnatal stem cells that give rise to oocytes in physiologically significant manner. It seems that few investigators are still chasing rare cells that are physiologically not significant.", "isRemoved"=>false, "created"=>"2012-08-01T03:36:36Z", "lastModified"=>"2012-08-01T03:36:36Z", "creator"=>{"userId"=>"276001"}, "highlightedText"=>"", "competingInterestStatement"=>{"creatorWasPrompted"=>true, "hasCompetingInterests"=>false}, "parentArticle"=>{"doi"=>"info:doi/10.1371/journal.pgen.1002848", "state"=>"published", "journals"=>{"PLoSGenetics"=>{"journalKey"=>"PLoSGenetics", "eIssn"=>"1553-7404", "title"=>"PLOS Genetics"}}}, "replyTreeSize"=>1, "mostRecentActivity"=>"2012-08-02T21:34:33Z", "replies"=>[{"type"=>"REPLY", "parentID"=>52451, "annotationUri"=>"info:doi/10.1371/reply/d807da6c-2a7f-4371-aea1-6ecd2db5b462", "title"=>"RE: Postnatal oocyte stem cells", "body"=>"Response to comment 1: the work of Shapiro and colleagues discussed in our Perspective is based on observations from studies of mice, not women; nonetheless, historical studies of women that have undergone surgical removal of one ovary are far from equivocal in terms of outcome. While some reports suggest a modest acceleration of time to menopause by a few years, other studies have failed to show any clear effect of hemiovariectomy on the timing of the menopausal transition. Even if the former occurs, it is puzzling that an acute reduction of the total ovarian reserve by 50% does not result in a more pronounced acceleration of the time to ovarian failure since the size of the ovarian reserve dictates the timing of menopause. Also, we never suggested that unilateral ovariectomy is not detrimental to the ovarian reserve; we only reviewed data and conclusions drawn by others in historical studies of the consequences of unilateral ovariectomy in rodents.\n\nComment 2: the new study from Kui Liu and colleagues in PNAS last month (109:12580-12585) was published after our Perspective was accepted and processed for publication. I am of course well aware of this work, and have several concerns with the experimental designs and conclusion drawn. The most significant of these is that the Ddx4-expressing cells from adult ovaries studied by Liu and colleagues (shown in Fig. 2B of their paper) are identified based on expression of a fluorescent marker in ALL germ cells rather than on differences in location of the endogenous Ddx4 protein. It has been reported and independently confirmed that oocytes retain the Ddx4 protein only in the cytoplasm whereas female germline or oogonial stem cells exhibit cell surface expression of the C-terminus of Ddx4 (Wu and colleagues, Nature Cell Biology 2009; Tilly and colleagues, Nature Medicine 2012). This property is how one can achieve isolation of viable oogonial stem cells away from contaminating oocytes (and all somatic cells). Since the genetic approach used by Liu and colleagues only identifies cells that have activated the Ddx4 gene promoter at some point (which drives the event that allows one to visualize the recombined germ cells by fluorescence analysis) but completely disregards where the endogenous Ddx4 protein is located at the time of cell collection, they cannot distinguish between different types of female germ cells. This is most apparent if one looks at the data shown in Figure 2B of their paper, which is the only figure that actually shows any data from their analysis of Ddx4-expressing cells present in dispersed adult mouse ovaries. Based on the scale bar shown, EVERY Ddx4-expressing cell shown in Figure 2B is an immature oocyte (oogonial stem cells are 5-8 micrometers in diameter, not 15-20 micrometers as is the case with the cells studied by Liu and colleagues). Hence, if one cultures the cells shown by Liu and colleagues in Figure 2B of their paper, it is no surprise that these cells will die off and not proliferate because they are immature oocytes. A straightforward PCR-based analysis of the Ddx4-expressing cells shown in Figure 2B of their paper would have confirmed this; yet, the paper is lacking an obvious and easy endpoint assessment of the actual identity of the Ddx4-expressing cells placed in culture. Simply based on cell size disparity, these fluorescent cells are not the mitotically active germline cells reported by ourselves and others.\n\nIt is also important to point out that Tilly and colleagues (Nature Medicine 2012) showed female germline or oogonial stem cells require several weeks of culture WITHOUT passage to establish visibly dividing germ cell colonies. Liu and colleagues examined their cultures only after a few days, or after early repeated passage which kills isolated oogonial stem cells. Hence, their inability to demonstrate the existence of mitotically-active germline cells in adult mouse ovaries is due to a combination of a reporter approach that fails to distinguish oocytes from oogonial stem cells (they are actually looking at cultured oocytes in Figure 2B of their paper; see above) along with the use of culture techniques that are not suitable for establishment and propagation of oogonial stem cells (suitable techniques are published).\n\nFinally, the remainder of the work shown after Figure 2 of the paper from Liu and colleagues focuses on cells isolated from the ovaries of their Ddx4-Cre reporter mice that are Ddx4-negative (viz. do not express the Ddx4 gene). Why Liu and colleagues elected to devote so much time and effort to prove that Ddx4-negative cells isolated from adult ovaries of their reporter mice are not germline progenitors, which is already inherent in the fact that the cells are Ddx4-negative to begin with [unlike the Ddx4-expressing cells independently isolated and characterized by Wu and colleagues (Nature Cell Biology 2009), Pacchiarotti and colleagues (Differentiation 2010), Tilly and colleagues (Nature Medicine 2012), and most recently Hua and colleagues (Cell Prolif 2012)], is unclear.\n\nBased on the above, the new study from Liu and colleagues falls short of proving or disproving anything with respect to the existence of mitotically-active germline cells in adult ovaries of mice as reported by several other laboratories. \n", "isRemoved"=>false, "created"=>"2012-08-02T21:34:33Z", "lastModified"=>"2012-08-02T21:34:33Z", "creator"=>{"userId"=>"129119"}, "highlightedText"=>"", "competingInterestStatement"=>{"creatorWasPrompted"=>true, "hasCompetingInterests"=>true, "body"=>"J.L. Tilly declares interest in intellectual property described in U.S. Patent 7,955,846 and is a co-founder of OvaScience, Inc."}, "parentArticle"=>{"doi"=>"info:doi/10.1371/journal.pgen.1002848", "state"=>"published", "journals"=>{"PLoSGenetics"=>{"journalKey"=>"PLoSGenetics", "eIssn"=>"1553-7404", "title"=>"PLOS Genetics"}}}, "replyTreeSize"=>0, "mostRecentActivity"=>"2012-08-02T21:34:33Z", "replies"=>[]}]}
• {"type"=>"COMMENT", "annotationUri"=>"info:doi/10.1371/annotation/669e2a73-7278-403b-bea7-be0da21d6af9", "title"=>"Thank you for your extraordinary work", "body"=>"Thank you for your discovery of OSCs in adult ovaries, and your ongoing work.\n\nPlease do all you can so that your discovery can result in a clinical treatment as soon as possible. So many of us are really hurting because of infertility. \n\nI have read all your recent papers, including the Woods etal, \"Purification of Oogonial Stem Cells From Adult Mouse and Human Ovaries: An Assessment of the Literature and a View Toward the Future\", Reproductive Science, Sep 2012. It is disappointing that work is being slowed down because of skepticism over OSCs. For example: \"With so many questions surrounding this new study, and the likelihood that no one else in the field will attempt to address them, valuable time and resources are now being redirected to pursuit of unplanned experiments in our laboratory...\". Also: \"Unfortunately, those skeptical of these cells continue to propound very negative views, which only serves to make it more difficult for scientists who study OSCs to obtain the funding needed to address the many questions about these cells that remain.\" If more labs worked with you on this extraordinary discovery, the time needed to get this research to a clinical application from which so many would benefit would be greatly reduced.\n\nI am aware of the current work of OvaScience to take the mitochondria from OSCs and to boost eggs by injecting into eggs at the same time as ICSI. This will benefit some, but is of no help to those of us who cannot even produce any eggs in stimulated IVF. The treatment we are waiting for is a treatment where a small amount of tissue is taken from the ovary cortex, and the OSCs are extracted and cultured in-vitro to produce eggs for IVF. It sounds like you are tantalisingly close - Dr. Tilly's lab is able to extract the OSCs, and Dr. Telfer is able to mature the eggs in-vitro. Please do all you can to bring this treatment to reality as soon as you can. \n\nI would travel to wherever in the world the treatment is being done, even if it is 5-10 years from now, I will be there. ", "isRemoved"=>false, "created"=>"2012-11-02T04:13:23Z", "lastModified"=>"2012-11-02T04:13:23Z", "creator"=>{"userId"=>"285965"}, "highlightedText"=>"", "competingInterestStatement"=>{"creatorWasPrompted"=>true, "hasCompetingInterests"=>false}, "parentArticle"=>{"doi"=>"info:doi/10.1371/journal.pgen.1002848", "state"=>"published", "journals"=>{"PLoSGenetics"=>{"journalKey"=>"PLoSGenetics", "eIssn"=>"1553-7404", "title"=>"PLOS Genetics"}}}, "replyTreeSize"=>0, "mostRecentActivity"=>"2012-11-02T04:13:23Z", "replies"=>[]}

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• {"id"=>"228608261216165890", "text"=>"More evidence against what we were all taught in biology, that women 'are born with all the eggs they'll ever have': http://t.co/p1hW6Zsf", "created_at"=>"2012-07-26T21:50:31Z", "user"=>"sxbegle", "user_name"=>"sharon begley", "user_profile_image"=>"http://a0.twimg.com/sticky/default_profile_images/default_profile_4_normal.png"}
• {"id"=>"228774374772199424", "text"=>"#PLOS: Oocyte Family Trees: Old Branches or New Stems? http://t.co/UFQ9zbAs", "created_at"=>"2012-07-27T08:50:36Z", "user"=>"PLOSGenetics", "user_name"=>"PLOS Genetics", "user_profile_image"=>"http://a0.twimg.com/profile_images/2435441933/pk712n4blw8kyf7yzqwc_normal.jpeg"}
• {"id"=>"228957725613236224", "text"=>"Do ovaries continue to produce eggs during adulthood? 07|26|12 …\nhttp://t.co/kMYpK4qr\n* http://t.co/032g45v0", "created_at"=>"2012-07-27T20:59:10Z", "user"=>"arkhangellohim", "user_name"=>"Gabriel Trujillo ", "user_profile_image"=>"http://a0.twimg.com/profile_images/1496264977/gabohhh_normal.jpg"}
• {"id"=>"229860591299338240", "text"=>"Muizen maken nieuwe #eicellen aan tijdens hun leven. Als dat ook voor #vrouwen geldt....#vruchtbaarheid\nhttp://t.co/Qi1klIrH", "created_at"=>"2012-07-30T08:46:50Z", "user"=>"Erfocentrum", "user_name"=>"@erfocentrum", "user_profile_image"=>"http://a0.twimg.com/profile_images/2041657743/logo3_normal.png"}
• {"id"=>"236828122790625280", "text"=>"New research sheds light on rethinking the biologic clock suggesting a woman may produce new eggs during her life. http://t.co/A5MRlRvQ", "created_at"=>"2012-08-18T14:13:19Z", "user"=>"drmarktrolice", "user_name"=>"Mark P. Trolice, MD", "user_profile_image"=>"http://a0.twimg.com/profile_images/1364823578/Dr_T_Shirt___Tie3_normal.JPG"}
• {"id"=>"254369226700255232", "text"=>"http://t.co/QmwmBGXr　ついに卵細胞の生成に成功したそうで．しかもiPsとES両方で．\" I just thought wow! \"だって．　コレ→http://t.co/VQWhI5Am　に続いて不妊治療に明るいニュース．", "created_at"=>"2012-10-05T23:55:24Z", "user"=>"videoniks", "user_name"=>"ryo fuzii", "user_profile_image"=>"http://a0.twimg.com/profile_images/535401927/videoniks300x300070404_normal.jpg"}
• {"id"=>"650457237580713984", "text"=>"Research shows mammals do continue to produce reproductive eggs!\nhttp://t.co/SzFxO9WZPQ", "created_at"=>"2015-10-03T23:47:45Z", "user"=>"nikauroom", "user_name"=>"Nikau Room", "user_profile_image"=>"http://pbs.twimg.com/profile_images/487418483072700417/PM9sl4Tr_normal.jpeg"}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/601415"], "description"=>"<p>(a) Following primordial germ cell (PGC) expansion starting at embryonic day 7.5 (e7.5) in the mouse, proliferation of female germ cells (oogonia; <i>pink</i>) ceases at e13.5 concomitant with a 5-day period of germ cell meiotic commitment that drives formation of oocytes (<i>blue</i>); since all oocytes produced during this time are of equivalent “depth”, the production-line hypothesis of postnatal oocyte maturation cannot logically explain increasing oocyte depth as females age. (b) If continued proliferation of OSCs (<i>red</i>) and their subsequent differentiation into oocytes (<i>blue</i>) during postnatal life is superimposed on the production-line hypothesis, the emerging picture is consistent with a progressive increase in oocyte depth in females as they age.</p>", "links"=>[], "tags"=>["oogenesis", "oogonial", "mitosis", "explains", "oocyte"], "article_id"=>271899, "categories"=>["Developmental Biology", "Information And Computing Sciences", "Mathematics", "Physiology", "Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Dori C. Woods", "Evelyn E. Telfer", "Jonathan L. Tilly"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002848.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Postnatal_oogenesis_through_ongoing_oogonial_stem_cell_OSC_mitosis_explains_increasing_oocyte_depth_with_age_/271899", "title"=>"Postnatal oogenesis through ongoing oogonial stem cell (OSC) mitosis explains increasing oocyte depth with age.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 01:44:36"}

PMC Usage Stats | Further Information

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Relative Metric

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F1000Prime