Table of Contents  
Year : 2015  |  Volume : 17  |  Issue : 3  |  Page : 415-420

Insights into female germ cell biology: from in vivo development to in vitro derivations

Department of Basic Medical Sciences, Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China

Date of Submission17-Sep-2014
Date of Decision23-Nov-2014
Date of Acceptance24-Nov-2014
Date of Web Publication23-Jan-2015

Correspondence Address:
Kehkooi Kee
Department of Basic Medical Sciences, Center for Stem Cell Biology and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1008-682X.148077

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Understanding the mechanisms of human germ cell biology is important for developing infertility treatments. However, little is known about the mechanisms that regulate human gametogenesis due to the difficulties in collecting samples, especially germ cells during fetal development. In contrast to the mitotic arrest of spermatogonia stem cells in the fetal testis, female germ cells proceed into meiosis and began folliculogenesis in fetal ovaries. Regulations of these developmental events, including the initiation of meiosis and the endowment of primordial follicles, remain an enigma. Studying the molecular mechanisms of female germ cell biology in the human ovary has been mostly limited to spatiotemporal characterizations of genes or proteins. Recent efforts in utilizing in vitro differentiation system of stem cells to derive germ cells have allowed researchers to begin studying molecular mechanisms during human germ cell development. Meanwhile, the possibility of isolating female germline stem cells in adult ovaries also excites researchers and generates many debates. This review will mainly focus on presenting and discussing recent in vivo and in vitro studies on female germ cell biology in human. The topics will highlight the progress made in understanding the three main stages of germ cell developments: namely, primordial germ cell formation, meiotic initiation, and folliculogenesis.

Keywords: embryonic stem cell; female germline stem cell; folliculogenesis; in vitro derivations; meiotic initiation; primordial germ cell

How to cite this article:
Jung D, Kee K. Insights into female germ cell biology: from in vivo development to in vitro derivations. Asian J Androl 2015;17:415-20

How to cite this URL:
Jung D, Kee K. Insights into female germ cell biology: from in vivo development to in vitro derivations. Asian J Androl [serial online] 2015 [cited 2022 Aug 10];17:415-20. Available from:

  Introduction Top

Although sperms and oocytes are derived from primordial germ cells (PGCs) formed in human fetuses, the key steps of their developments differ considerably after the formation of spermatogonia and oogonia. Male germ cells are arrested at mitotic stage in the fetal testis until puberty. When spermatogonial stem cells start to differentiate and enter meiosis, the human testis can produce hundred millions of sperm daily. In contrast, female germ cells begin with an endowment of about 5 million oogonia and then proceed to meiosis in the fetal ovary. However, the female ovary only produces one mature oocyte per menstrual period, and the total number of oocytes ovulated is about 456 if an individual starts to ovulate at age 12 and menopause at age 50. Therefore, the depletion of oogonia has been thought to be caused by a lack of female germline stem cells (GSCs) in the adult ovary.

Our understanding of female germ cell biology is mostly extrapolated from model organisms such as mice. A human system will give us a more precise understanding of human female germ cell development since there are many differences between animal and human germ cells. In vitro production of germ cells from pluripotent stem cells, including human embryonic stem cells (hESCs) and induced pluripotent stem cells, has provided an unprecedented opportunity to explore the cellular and molecular mechanisms of human germ cell biology. [1]-[7] Pluripotent stem cells are cells that can give rise to all three somatic lineages and the germ cell lineage. If these cells can be directed to differentiate into germ cell lineages, the process of germ cell biology can be studied from the early stages to the mature sperm or oocyte. On the other hand, developing and setting up an in vitro system that can mimic the in vivo developmental process require some basic knowledge of female germ cell biology. In this review, we first examined what we have learned from in vivo studies and compared them to the progress made by using in vitro systems.

Primordial germ cell development

Primordial germ cells are the embryonic precursors of the gametes. [8],[9] These cells are first identified in the proximal epiblast around the third week of human gestation. [8] Then, the PGC population gradually proliferates during PGC migration to gonadal ridges at 4-5 weeks. [10],[11] The transition of PGCs into gonocytes starts at 8 weeks of gestation, followed by sex-specific differentiation. [12] In the female gonads, oogonia generally enter meiosis and remain quiescent in the first meiotic prophase during embryonic development around week 12, whereas in the male, spermatogonia arrest in G0/G1 of mitosis and do not enter meiosis until puberty. [13]-[15]

Primordial germ cells specification

Several studies have proposed the extragonadal location of PGCs in human embryos. [8],[16],[17] Despite the first observations on the extragonadal location of PGCs, the exact mechanisms of signal interaction that controls the specification of PGCs in human is poorly understood. The mechanisms underlying PGC specification in mammals are relatively conserved. [18]-[21] Evidence from mice studies has demonstrated that bone morphogenetic protein 4 (BMP4) and BMP8b released from the extraembryonic ectoderm and BMP2 from the proximal visceral endoderm induce the formation of nascent PGCs. [21] Similar to these studies in mice, Childs et al. [20] demonstrated expression of genes encoding BMP ligands with an increase in the expression of BMP2 in the human fetal ovary. Human in vitro studies has also suggested that BMP4 along with BMP7 and BMP8b are necessary for human germ cell differentiation. [18] WNT signaling is also involved in PGC specification. [19] It has recently been reported that WNT3 and BMPs signaling pathway both contributed to activate BLIMP1 and PRDM14, which leads to the specification of PGCs. [22] The expression of these factors may indicate conserved roles in PGC specification. Consistent with the mouse studies, BLIMP1 is expressed in human fetal gonads and hESCs-derived germline cells. [23],[24] Recent work suggested that BLIMP1 is co-expressed with OCT4 in human PGC precursors, but not with the late germ cell marker, VASA. [25] Additionally, BLIMP1 may modulate the induction of germ cell specification by turning off SOX2 during early human development. [23] These findings suggest that BLIMP1 might act in a molecular switch to regulate the germline fates determination during early human development.


Primordial germ cells exit from the wall of the hindgut to incorporate into the extracellular matrix (ECM) of the dorsal mesentery. [26],[27] These cells are able to move actively through the ECM substrates to reach the gonadal crest. Several hypotheses explaining PGC migration to the gonad have been suggested. Migratory PGCs seem to interact with mesenchymal cells through ECM molecules, such as glycosaminoglycan and fibronectin. [26] These different types of proteoglycans may facilitate the migration of the PGCs. Chemoattractants, stem cell factor (SCF or c-Kit ligand) and stromal-derived factor-1, are also implicated in guiding PGCs to the gonad. [28],[29] Support for this hypothesis was provided by c-Kit receptor staining, which revealed that the receptor of c-Kit ligand is expressed in human PGCs. [29] A recent study has shown that human PGCs move together with autonomic nerve fibers and Schwann cells, and it is proposed that these nerve fibers may support the PGC migration. [30] During migration, human PGCs proliferate by mitotic divisions and they enter into a process of cell differentiation after colonization, and are known as oogonia and spermatogonia. [31],[32]

Sex determination and transition from primordial germ cells to oogonia

Sex determination in humans is not well understood at the molecular level. Mammalian sex determination is dependent on genetic control primarily induced by the chromosomal set with the presence or absence of a particular gene on the Y chromosome, SRY. [33] The malfunction of SRY is most likely responsible for some human XY disorders of sexual development. [34]-[36] For example, the reduction of WT1, a potential regulator of SRY, is associated with XY sex reversal (a case of Frasier syndrome). [36] Mouse studies showed that the expression of SRY in the genital ridges initiates testis formation by directing precursors of supporting cells to Sertoli cells rather than granulosa cells. [33],[37],[38] In addition, Foxl2 and Rspo1 seem to play important roles in female sex determination. [39]-[41] In experimental models, both XX Rspo1−/− gonads and XX Foxl2−/− gonads are associated with female-to-male sex reversal. [40]-[42] The regulation of germ cell proliferation is associated with forming of the functional unit of the ovary termed primordial follicle. [43],[44] Activin A, a member of the transforming growth factor-b family, has been shown to increase transiently the number of PGCs during the developmental period leading up to primordial follicle formation in human. [44] Hereafter, oogonia in the primordial follicle generally enter prophase of the first meiotic division, while spermatogonia do not enter meiosis until puberty. [45],[46]

In vitro induction of human primordial germ cells

Human embryonic stem-based systems that can recapitulate basic mechanisms of PGC specifications will provide a valuable platform to study human germ cell development. [1],[3],[5]-[7] The in vitro cell culture system of differentiation also gives us new chances to test extrinsic factors essential during human germ cell development, including growth factors that may induce germ cell formation or specifications. Studies in mice have demonstrated that the formation and specification of the mouse PGC precursor population are dependent on BMP2, BMP4 and BMP8b. [47]-[49] Additionally, mouse ESCs bearing BLIMP1 and Stella transgenes were induced into PGC-like cells by BMP signals and underwent oogenesis in reconstituted ovaries. [50] Using hESCs, researchers found that the signaling pathway of BMPs also functions to induce human PGCs. One study shows that BMP4, BMP7, BMP8b can promote PGC formation from hESCs in vitro. [18] In other studies, stimulation with other factors such as fibroblast growth factor 2 (FGF2), SCF or WNT3A also can enrich the germ cell-like population. [7],[51],[52]

Induction of PGCs in differentiated hESCs opens the door to study human PGC in vitro, but it is necessary to isolate the PGC populations from a mixed population of different cell lineages. A reporter system, in which the promoter of a germ-cell specific gene, VASA (or DDX), is connected to a fluorescent protein, was constructed to accomplish this goal. [3] Under BMP induction, about 5% of the differentiated population expressed green fluorescent protein (GFP) and also express other PGC markers. These in vitro derived human PGCs were hypomethylated and proliferated slowly on inactivated mouse embryonic fibroblasts. Using this system, the researchers determined the genetic requirement of PGC formation and found that human DAZL was required for PGC formation. Another study showed that ectopic expression of VASA in human ESCs promoted PGCs formation and progression through meiosis. [53]

Meiotic progression

From late primordial germ cells to initiation of meiosis

Two independent groups reported that retinoic acid (RA) plays an important role in initiating meiosis in mice. [54],[55] RA, which is produced by the mesonephros of both sexes, may play a role in the initiation of meiosis. [56] RA induces Stra8, the meiotic gatekeeper gene, in ovarian germ cells, while in the testicular germ cells this is prevented by the RA-degrading enzyme CYP26B1. However, a recent study with Raldh2−/− mice lacking RA activity has shown that Stra8 and meiosis markers, SYCP3 and gH2AX, were detectable in the fetal ovary. [57] The authors suggested that CYP26B1 might inhibit the meiosis initiation by degrading an unknown inducer of Stra8 other than RA in the testis. Although meiosis seems to be a prerequisite event of folliculogenesis, a recent study in mice using Stra8 knockout mice indicated that the folliculogenesis can proceed in the absence of the meiosis initiation. [58] The principal mechanisms and potential inducers other than RA that govern meiotic initiation and folliculogenesis remain to be elucidated.

Only a few studies have reported meiotic initiation in human fetal gonad. [32],[46],[59] In contrast to mice, the developmental stages of the germ cells in the human fetal ovary are much less synchronized. Recent findings in the fetal human gonad suggested that RA is a possible intrinsic factor involved in meiosis entry in the human ovary. [46],[59] Subsequently, STRA8 was up-regulated in response to RA, followed by the induction of SYCP3 and DMC in the fetal human gonad. Surprisingly, the expression of CYP26B1 was not significantly different between ovaries and testes. This suggested that the role of CYP26B1 in the regulation of meiosis may not be the major mechanism of meiosis inhibition in the human fetal testis. One previous study investigated the expression pattern of DMRT1 in the human fetal ovaries. [32] These results suggested that there is a transient up-regulation of DMRT1 in human fetal ovary prior to initiation of meiosis. Taken together, these findings hint that the detailed mechanisms of meiosis in humans might be different from that previously described in mice.

Meiotic recombination

Once meiosis is initiated, meiotic recombination is promoted by meiosis-specific regulatory networks. Genes involved in the formation of a chromosomal scaffold and recombination, such as REC8, SPO11, DMC1, SYCP1, SYCP2, SYCP3, and MLH1 are essential for meiotic progression. [32],[60],[61] During the first meiotic division, double-strand breaks (DSBs) in DNA can induce crossing over between homologous chromosomes, followed by the recruitment of meiotic-specific proteins to DSBs sites that are involved in meiotic recombination. [62] PRDM9 has recently been identified as the major determinant in specifying meiotic recombination hot spots in mouse and human. [63],[64] Further study showed that the variation in the zinc finger domain of PRDM9 affects DSB loci distribution and outcomes of meiotic recombinations in human sperm. [65] Zheng et al. [66] analyzed the global functional network by integrating diverse genomic datasets to understand the meiotic initiation and progression in the human fetal ovary. The authors found that meiosis-specific genes are highly clustered with themselves compared to low clustering of meiosis-nonspecific genes. Interestingly, DAZL was identified as a novel meiotic-initiation gene in this study, in accordance with its role in mice. Very recently, DAZL and BOULE were found to show distinct spatio-temporal expression patterns during meiosis in human fetal ovaries, in contrast to their co-expression pattern in mouse fetal ovaries. [67] Again, these recent studies found a common principal of meiotic progression in mouse and human ovary, but subtle differences were also significant.

In vitro induction of meiosis

Until date, a few studies reported successful in vitro induction of meiotic progression from undifferentiated human stem cells. Clark et al. [1] observed an increase in transcriptional expression of meiotic makers when hESCs were induced to differentiate by fetal bovine serum, but failed to detect clear synaptonemal complex formation and MLH1 foci. Meiotic initiation marked by gH2AX and meiotic prophase indicated by elongated SYCP3 staining were detected in an independent study when DAZL, BOULE or DAZ was overexpressed in hESCs. [3] Moreover, a small percentage of haploid spermatids could be isolated in the differentiated cultures, suggesting a completion of meiosis in the male cell lines. In the same study, about 20% of female hESCs were induced to enter into meiotic prophase, but no follicle-like cells was detected.


The primary oocytes that are arrested at the prophase stage of the first meiotic division synthesize and accumulate RNAs and proteins for oocyte growth and maturation. [68],[69] Byskov et al. found that a group of sterols, termed meiosis activating sterols, were able to induce oocyte maturation in vitro. [70],[71] These sterols are most likely acting downstream of follicle-stimulating hormone (FSH) signaling pathway to induce oocyte maturation. In addition, communication between oocytes and their surrounding granulosa cells are crucial at all stages of folliculogenesis, both for oocyte maturation and for granulosa cells differentiation. [72],[73] Oogonial nests surrounded by somatic cells and those cells may have consequences for the activating cues in primordial follicle formation. [44] Communication between oocyte and surrounding granulosa cells through autocrine, endocrine, and paracrine manners coordinate further development of ovarian follicle. [74]-[76] Subsequently, primordial follicles are activated and further develop into primary follicle or more mature follicles. [77]

During the transitions from primordial to antral follicles, many molecular mechanisms must be tightly controlled in order to produce mature and functional oocytes. [78]-[80] The phosphoinositide 3 kinase (PI3K)-protein kinase B (Akt) signaling pathway leads to primordial follicle survival and growth, whereas PTEN is a negative regulator of the PI3K pathway. [79],[80] In a mouse model, a deficiency in NOBOX, an ovary-specific gene, leads to decreased expression of many major oocyte transcripts, such as OCT4, FGF8, Zar1, growth differentiation factor 9 (GDF9), Bmp15, and H1foo. [69],[81] Consistent with the mouse studies, misregulation of NOBOX is associated with premature ovarian failure (POF) in human. [82] Thus, both PTEN/PI3K signaling pathway and NOBOX are crucial in the regulation of early oogenesis and folliculogenesis. Until date, only a few transcriptional factors, such as FIGLA and NOBOX, have been associated with oocyte development. [83],[84] It has been reported that TATA-binding protein 2 (TBP2) is involved in mouse oocyte development. [85],[86] TBP2-deficient mice show a decreased number of secondary follicles and reveal an altered expression of GDF9, Bmp15, ZP3, and H1foo. Although the role of TBP2 has not yet been elucidated in human, enrichment of TBP2 in the ovary is conserved in vertebrates. Altogether, the above studies suggest a potential role for TBP2 in the human folliculogenesis.

Bidirectional communications of oocyte and granulosa cells

The bidirectional communication between oocytes and its surrounding somatic cells is essential for the differentiation and maturation of ovarian follicle compartments. [72],[73] The complex intraovarian mechanisms have been implicated in this process as ovarian paracrine or autocrine regulators. In particular, GDF9 and BMP15 are principal participants of follicular development and fertility. [87]-[89] In humans, missense mutations in GDF9 and a point mutation in BMP15 have been associated with POF. [89]-[91] Extensive studies of GDF9 and BMP15 have been carried out in mutant animal models. GDF9-deficient mice exhibit growth arrest at the primary follicle stage similar to the human phenotype; [92] in contrast, Bmp15 knockout mice are subfertile, but patients carrying mutations of BMP15 exhibit severe reproductive defects. [89],[93] The differences in mutants phenotype of mice versus phenotypes associated with human BMP15 mutations might be owing to specie-specific differences between monoovulatory human and polyovulatory mice. [94] Granulosa cell proliferation and antral cavity accumulation within preantral follicles ultimately give rise to antral follicles. Unlike in earlier stages, growing follicles in their late stages express functional FSH and luteinizing hormone (LH) receptors which are able to respond to gonadotropins. [95] The surge of gonadotropins, FSH and LH, initiate a cascade of events leading to follicular rupture and oocyte release. [96]

In vitro derivations of oocytes

Although in vitro derivation of human oocytes or follicles from stem cells is a much anticipated advance in human reproduction, there has been no successful report so far. Even in mouse studies, only a few studies have shown progress in deriving oocytes from mouse stem cells. The first exciting report was done by Hόbner et al. [97] in 2003, in which follicle-like aggregates were found in the suspension of a spontaneously differentiated culture. These aggregates expressed GDF9 mRNA transcript and estradiols. The isolated oocyte-like cells also expressed zona pellucida proteins ZP2 and ZP3; however, no offspring was reported in this study. The most recent report by Hayashi et al. showed the generation of fertilizable oocytes from PGC-like cells derived from mouse ES cells. [50] This was achieved by isolating PGC-like cells induced from mouse epiblast stem cells, followed by their aggregation with fetal ovaries and transplantation into mouse ovarian bursa. Moreover, offspring were produced by in vitro fertilization of the derived oocytes. Hence, the later report required an aggregation and transplantation step that would not be feasible if this were to be extended to human oocyte derivations.

Despite reported studies performed with human ES cells, human oocyte-like cells have a limited capability to generate mature and functional oocytes. For instance, Liu et al. suggested that pluripotent human amniotic fluid cells (HuAFCs) have the potential to differentiate into oocyte-like cells in vitro. [98] Furthermore, the oocyte-like cells from HuAFCs express DMC1, SCP3, DAZL, ZP3 and GDF9. Many attempts need to be carried out to achieve in vitro derivations of functional oocyte or follicles.

Existence of female germline stem cells in adult ovary

Recently, the central dogma of female reproductive biology has been challenged by some surprising observations. Female GSCs exist in lower species, such as invertebrates, fish, and birds, and possess the capacity to provide a reservoir of oogonia to generate new oocytes in the adult ovaries; [99],[100] however, no GSCs have been found in the mammalian adult ovary. In 2004, Johnson et al. [101] concluded that female GSCs existed in the postnatal mammalian ovary and that this population can give rise to functional oocytes under certain conditions. A study was done in mice and is based on the morphological appearance and immunological detection of the germline-specific marker (mouse VASA homolog, also known as VASA homolog) to isolate a fraction of GSCs from dispersed ovaries. Follow-up studies documented rare mitotically active cells with germline characteristics in post-menopausal woman that spontaneously form oocyte-like cells in vitro and in vivo. [102] Zou et al. [103] offered additional evidence for the existence of GSCs in the adult mammalian females, by allowing a retrovirus to carry the expression of GFP in female GSCs prior to transplantation. Another follow-up study showed that GFP-expressing oocytes were observed in chemo-ablated mice transplanted with female GSCs; [104] and the authors concluded that the oocytes came from circulating GSCs from bone marrow. However, these results raised doubts and generated debates on whether the methods used to examine the existence of GSCs were reliable. [105] Following these initial reports supporting the existence of GSCs in postnatal ovaries, many researchers attempted to verify the results but found opposite conclusions. First, Eggan et al. [106] found no circulating ovulated oocytes from circulating cells of bone marrow by using the parabiotic mouse model approach.Two other studies looking for mitotically active GSCs in mice also clearly showed that there are no postnatal GSCs in mouse ovaries. [107],[108] Byskov et al. described that oogonia and some diplotene oocytes exists in the first-trimester human ovaries. [109] In perinatal ovaries, a few oogonia, numerous diplotene oocytes, and follicles formation were observed. However, the researchers found no oogonia in postnatal human ovaries older than 2 years. Therefore, the existence of GSCs in postnatal ovary remains ambiguous.

  Future perspective Top

Studies of in vitro derived germ cells, using different methodologies, have made possible to delineate some functional signatures indicative of human female germ cell development. [2],[110],[111],[112],[113],[114],[115],[116],[117],[118],[119],[120] However, there are technical challenges to overcome and to develop in the in vitro differentiation system. For instance, the efficiency of derivation of PGCs from hESC and completion of meiosis are still relatively low in in vitro systems. Finally, somatic cells surrounding germ cells in gonads may be needed for in vitro maturation of human gametes. Stepwise construction of an in vitro differentiation system consisting of germ cells and somatic cells may yield the most fruitful progress to mimic in vivo development of human germ cells. Indeed, a more detailed understanding of the mechanisms of human germ cell development and its interaction with the gonadal niche is central to develop more effective differentiation systems. Meanwhile, studies using model organisms such as mice and conventional studies of human reproductive biology may help us to build the in vitro system.

Even though the advance of in vitro systems for human reproduction is still limited, efforts to improve the efficiency should be continued because of the unprecedented opportunity we can explore to understand human germ cell biology, as well as for the therapeutic potential in regenerative medicine.

  Author contributions Top

DJ and KK designed and wrote the manuscript.

  Acknowledgments Top

This work is supported by the Chinese National Natural Science Foundation [Grant number: 31171429]; and the Chinese Ministry of Science and Technology [Grant number: 2013CB947903]. D.J. is supported by The Research Fellowship for International Young Scientists of the Chinese National Natural Science Foundation {31150110461, 31250110574}.

  References Top

Clark AT, Bodnar MS, Fox M, Rodriquez RT, Abeyta MJ, et al. Spontaneous differentiation of germ cells from human embryonic stem cells in vitro. Hum Mol Genet 2004; 13: 727-39.  Back to cited text no. 1
Tilgner K, Atkinson SP, Golebiewska A, Stojkovic M, Lako M, et al. Isolation of primordial germ cells from differentiating human embryonic stem cells. Stem Cells 2008; 26: 3075-85.  Back to cited text no. 2
Kee K, Angeles VT, Flores M, Nguyen HN, Reijo Pera RA. Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation. Nature 2009; 462: 222-5.  Back to cited text no. 3
Bucay N, Yebra M, Cirulli V, Afrikanova I, Kaido T, et al. A novel approach for the derivation of putative primordial germ cells and sertoli cells from human embryonic stem cells. Stem Cells 2009; 27: 68-77.  Back to cited text no. 4
Panula S, Medrano JV, Kee K, Bergström R, Nguyen HN, et al. Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells. Hum Mol Genet 2011; 20: 752-62.  Back to cited text no. 5
Easley CA 4 th , Phillips BT, McGuire MM, Barringer JM, Valli H, et al. Direct differentiation of human pluripotent stem cells into haploid spermatogenic cells. Cell Rep 2012; 2: 440-6.  Back to cited text no. 6
Chuang CY, Lin KI, Hsiao M, Stone L, Chen HF, et al. Meiotic competent human germ cell-like cells derived from human embryonic stem cells induced by BMP4/WNT3A signaling and OCT4/EpCAM (epithelial cell adhesion molecule) selection. J Biol Chem 2012; 287: 14389-401.  Back to cited text no. 7
Eddy EM, Clark JM, Gong D, Fenderson BA. Origin and migration of primordial germ-cells in mammals. Gamete Res 1981; 4: 333-62.  Back to cited text no. 8
De Felici M. Germ stem cells in the mammalian adult ovary: considerations by a fan of the primordial germ cells. Mol Hum Reprod 2010; 16: 632-6.  Back to cited text no. 9
Pereda J, Zorn T, Soto-Suazo M. Migration of human and mouse primordial germ cells and colonization of the developing ovary: an ultrastructural and cytochemical study. Microsc Res Tech 2006; 69: 386-95.  Back to cited text no. 10
Mamsen LS, Brøchner CB, Byskov AG, Møllgard K. The migration and loss of human primordial germ stem cells from the hind gut epithelium towards the gonadal ridge. Int J Dev Biol 2012; 56: 771-8.  Back to cited text no. 11
Motta PM, Makabe S, Nottola SA. The ultrastructure of human reproduction. I. The natural history of the female germ cell: origin, migration and differentiation inside the developing ovary. Hum Reprod Update 1997; 3: 281-95.  Back to cited text no. 12
Sathananthan AH, Selvaraj K, Trounson A. Fine structure of human oogonia in the foetal ovary. Mol Cell Endocrinol 2000; 161: 3-8.  Back to cited text no. 13
Stoop H, Honecker F, Cools M, de Krijger R, Bokemeyer C, et al. Differentiation and development of human female germ cells during prenatal gonadogenesis: an immunohistochemical study. Hum Reprod 2005; 20: 1466-76.  Back to cited text no. 14
Bowles J, Koopman P. Sex determination in mammalian germ cells: extrinsic versus intrinsic factors. Reproduction 2010; 139: 943-58.  Back to cited text no. 15
Ullmann SL, Shaw G, Alcorn GT, Renfree MB. Migration of primordial germ cells to the developing gonadal ridges in the tammar wallaby Macropus eugenii. J Reprod Fertil 1997; 110: 135-43.  Back to cited text no. 16
Goto T, Adjaye J, Rodeck CH, Monk M. Identification of genes expressed in human primordial germ cells at the time of entry of the female germ line into meiosis. Mol Hum Reprod 1999; 5: 851-60.  Back to cited text no. 17
Kee K, Gonsalves JM, Clark AT, Pera RA. Bone morphogenetic proteins induce germ cell differentiation from human embryonic stem cells. Stem Cells Dev 2006; 15: 831-7.  Back to cited text no. 18
Ohinata Y, Ohta H, Shigeta M, Yamanaka K, Wakayama T, et al. A signaling principle for the specification of the germ cell lineage in mice. Cell 2009; 137: 571-84.  Back to cited text no. 19
Childs AJ, Kinnell HL, Collins CS, Hogg K, Green SJ, et al. BMP signalling in the human fetal ovary is developmentally-regulated and promotes primordial germ cell apoptosis. Aust N Z J Obstet Gynecol 2010; 50: 28.  Back to cited text no. 20
Young JC, Dias VL, Loveland KL. Defining the window of germline genesis in vitro from murine embryonic stem cells. Biol Reprod 2010; 82: 390-401.  Back to cited text no. 21
Aramaki S, Hayashi K, Kurimoto K, Ohta H, Yabuta Y, et al. A mesodermal factor, T, specifies mouse germ cell fate by directly activating germline determinants. Dev Cell 2013; 27: 516-29.  Back to cited text no. 22
Lin IY, Chiu FL, Yeang CH, Chen HF, Chuang CY, et al. Suppression of the SOX2 neural effector gene by PRDM1 promotes human germ cell fate in embryonic stem cells. Stem Cell Reports 2014; 2: 189-204.  Back to cited text no. 23
Eckert D, Biermann K, Nettersheim D, Gillis AJ, Steger K, et al. Expression of BLIMP1/PRMT5 and concurrent histone H2A/H4 arginine 3 dimethylation in fetal germ cells, CIS/IGCNU and germ cell tumors. BMC Dev Biol 2008; 8: 106.  Back to cited text no. 24
Gkountela S, Li Z, Vincent JJ, Zhang KX, Chen A, et al. The ontogeny of cKIT+human primordial germ cells proves to be a resource for human germ line reprogramming, imprint erasure and in vitro differentiation. Nat Cell Biol 2013; 15: 113-22.  Back to cited text no. 25
Pereda J, Zorn T M, Soto M, Motta PM. Morphological and cytochemical study of extracellular matrix during the migratory phase of human and mouse primordial germ cells. Ital J Anat Embryol 1998; 103 (4 Suppl 1): 41-50..  Back to cited text no. 26
Richardson BE, Lehmann R. Mechanisms guiding primordial germ cell migration: strategies from different organisms. Nat Rev Mol Cell Biol 2010; 11: 37-49.  Back to cited text no. 27
Molyneaux KA, Zinszner H, Kunwar PS, Schaible K, Stebler J, et al. The chemokine SDF1/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival. Development 2003; 130: 4279-86.  Back to cited text no. 28
Høyer PE, Byskov AG, Møllgård K. Stem cell factor and c-Kit in human primordial germ cells and fetal ovaries. Mol Cell Endocrinol 2005; 234: 1-10.  Back to cited text no. 29
Møllgård K, Jespersen A, Lutterodt MC, Yding Andersen C, Høyer PE, et al. Human primordial germ cells migrate along nerve fibers and Schwann cells from the dorsal hind gut mesentery to the gonadal ridge. Mol Hum Reprod 2010; 16: 621-31.  Back to cited text no. 30
Baker TG. A quantitative and cytological study of germ cells in human ovaries. Proc R Soc Lond B Biol Sci 1963; 158: 417-33.  Back to cited text no. 31
Jørgensen A, Nielsen JE, Blomberg Jensen M, Græm N, Rajpert-De Meyts E. Analysis of meiosis regulators in human gonads: a sexually dimorphic spatio-temporal expression pattern suggests involvement of DMRT1 in meiotic entry. Mol Hum Reprod 2012; 18: 523-34.  Back to cited text no. 32
Kashimada K, Koopman P. Sry: the master switch in mammalian sex determination. Development 2010; 137: 3921-30.  Back to cited text no. 33
Schumacher V, Gueler B, Looijenga LH, Becker JU, Amann K, et al. Characteristics of testicular dysgenesis syndrome and decreased expression of SRY and SOX9 in Frasier syndrome. Mol Reprod Dev 2008; 75: 1484-94.  Back to cited text no. 34
McElreavy K, Vilain E, Abbas N, Costa JM, Souleyreau N, et al. XY sex reversal associated with a deletion 5' to the SRY "HMG box" in the testis-determining region. Proc Natl Acad Sci U S A 1992; 89: 11016-20.  Back to cited text no. 35
Hossain A, Saunders GF. The human sex-determining gene SRY is a direct target of WT1. J Biol Chem 2001; 276: 16817-23.  Back to cited text no. 36
Albrecht KH, Eicher EM. Evidence that Sry is expressed in pre-Sertoli cells and Sertoli and granulosa cells have a common precursor. Dev Biol 2001; 240: 92-107.  Back to cited text no. 37
Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R. Male development of chromosomally female mice transgenic for Sry. Nature 1991; 351: 117-21.  Back to cited text no. 38
Crisponi L, Deiana M, Loi A, Chiappe F, Uda M, et al. The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. Nat Genet 2001; 27: 159-66.  Back to cited text no. 39
Parma P, Radi O, Vidal V, Chaboissier MC, Dellambra E, et al. R-spondin1 is essential in sex determination, skin differentiation and malignancy. Nat Genet 2006; 38: 1304-9.  Back to cited text no. 40
Auguste A, Chassot AA, Grégoire EP, Renault L, Pannetier M, et al. Loss of R-spondin1 and Foxl2 amplifies female-to-male sex reversal in XX mice. Sex Dev 2011; 5: 304-17.  Back to cited text no. 41
Garcia-Ortiz JE, Pelosi E, Omari S, Nedorezov T, Piao Y, et al. Foxl2 functions in sex determination and histogenesis throughout mouse ovary development. BMC Dev Biol 2009; 9: 36.  Back to cited text no. 42
Hirshfield AN. Development of follicles in the mammalian ovary. Int Rev Cytol 1991; 124: 43-101.  Back to cited text no. 43
Martins da Silva SJ, Bayne RA, Cambray N, Hartley PS, McNeilly AS, et al. Expression of activin subunits and receptors in the developing human ovary: activin A promotes germ cell survival and proliferation before primordial follicle formation. Dev Biol 2004; 266: 334-45.  Back to cited text no. 44
Kimble J, Page DC. The mysteries of sexual identity. The germ cell's perspective. Science 2007; 316: 400-1.  Back to cited text no. 45
Le Bouffant R, Guerquin MJ, Duquenne C, Frydman N, Coffigny H, et al. Meiosis initiation in the human ovary requires intrinsic retinoic acid synthesis. Hum Reprod 2010; 25: 2579-90.  Back to cited text no. 46
Lawson KA, Dunn NR, Roelen BA, Zeinstra LM, Davis AM, et al. Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev 1999; 13: 424-36.  Back to cited text no. 47
Ying Y, Qi X, Zhao GQ. Induction of primordial germ cells from murine epiblasts by synergistic action of BMP4 and BMP8B signaling pathways. Proc Natl Acad Sci U S A 2001; 98: 7858-62.  Back to cited text no. 48
Ying Y, Zhao GQ. Cooperation of endoderm-derived BMP2 and extraembryonic ectoderm-derived BMP4 in primordial germ cell generation in the mouse. Dev Biol 2001; 232: 484-92.  Back to cited text no. 49
Hayashi K, Ogushi S, Kurimoto K, Shimamoto S, Ohta H, et al. Offspring from oocytes derived from in vitro primordial germ cell-like cells in mice. Science 2012; 338: 971-5.  Back to cited text no. 50
Tu J, Fan L, Tao K, Zhu W, Li J, et al. Stem cell factor affects fate determination of human gonocytes in vitro. Reproduction 2007; 134: 757-65.  Back to cited text no. 51
Kjartansdóttir KR, Gabrielsen A, Reda A, Söder O, Bergström-Tengzelius R, et al. Differentiation of stem cells upon deprivation of exogenous FGF2: a general approach to study spontaneous differentiation of hESCs in vitro. Syst Biol Reprod Med 2012; 58: 330-8.  Back to cited text no. 52
Medrano JV, Ramathal C, Nguyen HN, Simon C, Reijo Pera RA. Divergent RNA-binding proteins, DAZL and VASA, induce meiotic progression in human germ cells derived in vitro. Stem Cells 2012; 30: 441-51.  Back to cited text no. 53
Bowles J, Knight D, Smith C, Wilhelm D, Richman J, et al. Retinoid signaling determines germ cell fate in mice. Science 2006; 312: 596-600.  Back to cited text no. 54
Koubova J, Menke DB, Zhou Q, Capel B, Griswold MD, et al. Retinoic acid regulates sex-specific timing of meiotic initiation in mice. Proc Natl Acad Sci U S A 2006; 103: 2474-9.  Back to cited text no. 55
Bowles J, Koopman P. Retinoic acid, meiosis and germ cell fate in mammals. Development 2007; 134: 3401-11.  Back to cited text no. 56
Kumar S, Chatzi C, Brade T, Cunningham TJ, Zhao X, et al. Sex-specific timing of meiotic initiation is regulated by Cyp26b1 independent of retinoic acid signalling. Nat Commun 2011; 2: 151.  Back to cited text no. 57
Dokshin GA, Baltus AE, Eppig JJ, Page DC. Oocyte differentiation is genetically dissociable from meiosis in mice. Nat Genet 2013; 45: 877-83.  Back to cited text no. 58
Childs AJ, Cowan G, Kinnell HL, Anderson RA, Saunders PT. Retinoic Acid signalling and the control of meiotic entry in the human fetal gonad. PLoS One 2011; 6: e20249.  Back to cited text no. 59
Lenzi ML, Smith J, Snowden T, Kim M, Fishel R, et al. Extreme heterogeneity in the molecular events leading to the establishment of chiasmata during meiosis i in human oocytes. Am J Hum Genet 2005; 76: 112-27.  Back to cited text no. 60
Vallente RU, Cheng EY, Hassold TJ. The synaptonemal complex and meiotic recombination in humans: new approaches to old questions. Chromosoma 2006; 115: 241-9.  Back to cited text no. 61
Gruhn JR, Rubio C, Broman KW, Hunt PA, Hassold T. Cytological studies of human meiosis: sex-specific differences in recombination originate at, or prior to, establishment of double-strand breaks. PLoS One 2013; 8: e85075.  Back to cited text no. 62
Baudat F, Buard J, Grey C, Fledel-Alon A, Ober C, et al. PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice. Science 2010; 327: 836-40.  Back to cited text no. 63
Myers S, Bowden R, Tumian A, Bontrop RE, Freeman C, et al. Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination. Science 2010; 327: 876-9.  Back to cited text no. 64
Berg IL, Neumann R, Lam KW, Sarbajna S, Odenthal-Hesse L, et al. PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans. Nat Genet 2010; 42: 859-63.  Back to cited text no. 65
Zheng P, Griswold MD, Hassold TJ, Hunt PA, Small CL, et al. Predicting meiotic pathways in human fetal oogenesis. Biol Reprod 2010; 82: 543-51.  Back to cited text no. 66
He J, Stewart K, Kinnell HL, Anderson RA, Childs AJ. A developmental stage-specific switch from DAZL to BOLL occurs during fetal oogenesis in humans, but not mice. PLoS One 2013; 8: e73996.  Back to cited text no. 67
Eichenlaub-Ritter U, Peschke M. Expression in in-vivo and in-vitro growing and maturing oocytes: focus on regulation of expression at the translational level. Hum Reprod Update 2002; 8: 21-41.  Back to cited text no. 68
Sánchez F, Smitz J. Molecular control of oogenesis. Biochim Biophys Acta 2012; 1822: 1896-912.  Back to cited text no. 69
Byskov AG, Andersen CY, Nordholm L, Thøgersen H, Xia G, et al. Chemical structure of sterols that activate oocyte meiosis. Nature 1995; 374: 559-62.  Back to cited text no. 70
Byskov AG, Andersen CY, Leonardsen L. Role of meiosis activating sterols, MAS, in induced oocyte maturation. Mol Cell Endocrinol 2002; 187: 189-96.  Back to cited text no. 71
Gilchrist RB, Ritter LJ, Armstrong DT. Oocyte-somatic cell interactions during follicle development in mammals. Anim Reprod Sci 2004; 82-83: 431-46.  Back to cited text no. 72
Chang CL, Wang HS, Soong YK, Huang SY, Pai SY, et al. Regulation of oocyte and cumulus cell interactions by intermedin/adrenomedullin 2. J Biol Chem 2011; 286: 43193-203.  Back to cited text no. 73
Canipari R. Oocyte - granulosa cell interactions. Hum Reprod Update 2000; 6: 279-89.  Back to cited text no. 74
Eppig JJ, Wigglesworth K, Pendola FL. The mammalian oocyte orchestrates the rate of ovarian follicular development. Proc Natl Acad Sci U S A 2002; 99: 2890-4.  Back to cited text no. 75
Gittens JE, Barr KJ, Vanderhyden BC, Kidder GM. Interplay between paracrine signaling and gap junctional communication in ovarian follicles. J Cell Sci 2005; 118: 113-22.  Back to cited text no. 76
Fortune JE. The early stages of follicular development: activation of primordial follicles and growth of preantral follicles. Anim Reprod Sci 2003; 78: 135-63.  Back to cited text no. 77
Adhikari D, Zheng W, Shen Y, Gorre N, Hämäläinen T, et al. Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles. Hum Mol Genet 2010; 19: 397-410.  Back to cited text no. 78
Reddy P, Zheng W, Liu K. Mechanisms maintaining the dormancy and survival of mammalian primordial follicles. Trends Endocrinol Metab 2010; 21: 96-103.  Back to cited text no. 79
Kim JY. Control of ovarian primordial follicle activation. Clin Exp Reprod Med 2012; 39: 10-4.  Back to cited text no. 80
Rajkovic A, Pangas SA, Ballow D, Suzumori N, Matzuk MM. NOBOX deficiency disrupts early folliculogenesis and oocyte-specific gene expression. Science 2004; 305: 1157-9.  Back to cited text no. 81
Qin Y, Choi Y, Zhao H, Simpson JL, Chen ZJ, et al. NOBOX homeobox mutation causes premature ovarian failure. Am J Hum Genet 2007; 81: 576-81.  Back to cited text no. 82
Huntriss J, Gosden R, Hinkins M, Oliver B, Miller D, et al. Isolation, characterization and expression of the human factor in the germline alpha (FIGLA) gene in ovarian follicles and oocytes. Mol Hum Reprod 2002; 8: 1087-95.  Back to cited text no. 83
Tripurani SK, Lee KB, Wang L, Wee G, Smith GW, et al. A novel functional role for the oocyte-specific transcription factor newborn ovary homeobox (NOBOX) during early embryonic development in cattle. Endocrinology 2011; 152: 1013-23.  Back to cited text no. 84
Gazdag E, Rajkovic A, Torres-Padilla ME, Tora L. Analysis of TATA-binding protein 2 (TBP2) and TBP expression suggests different roles for the two proteins in regulation of gene expression during oogenesis and early mouse development. Reproduction 2007; 134: 51-62.  Back to cited text no. 85
Gazdag E, Santenard A, Ziegler-Birling C, Altobelli G, Poch O, et al. TBP2 is essential for germ cell development by regulating transcription and chromatin condensation in the oocyte. Genes Dev 2009; 23: 2210-23.  Back to cited text no. 86
Vitt UA, Hsueh AJ. Stage-dependent role of growth differentiation factor-9 in ovarian follicle development. Mol Cell Endocrinol 2001; 183: 171-7.  Back to cited text no. 87
Wu YT, Tang L, Cai J, Lu XE, Xu J, et al. High bone morphogenetic protein-15 level in follicular fluid is associated with high quality oocyte and subsequent embryonic development. Hum Reprod 2007; 22: 1526-31.  Back to cited text no. 88
Otsuka F, McTavish KJ, Shimasaki S. Integral role of GDF-9 and BMP-15 in ovarian function. Mol Reprod Dev 2011; 78: 9-21.  Back to cited text no. 89
Laissue P, Christin-Maitre S, Touraine P, Kuttenn F, Ritvos O, et al. Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure. Eur J Endocrinol 2006; 154: 739-44.  Back to cited text no. 90
Tiotiu D, Alvaro Mercadal B, Imbert R, Verbist J, Demeestere I, et al. Variants of the BMP15 gene in a cohort of patients with premature ovarian failure. Hum Reprod 2010; 25: 1581-7.  Back to cited text no. 91
Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, et al. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 1996; 383: 531-5.  Back to cited text no. 92
Yan C, Wang P, DeMayo J, DeMayo FJ, Elvin JA, et al. Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol 2001; 15: 854-66.  Back to cited text no. 93
Hashimoto O, Moore RK, Shimasaki S. Posttranslational processing of mouse and human BMP-15: potential implication in the determination of ovulation quota. Proc Natl Acad Sci U S A 2005; 102: 5426-31.  Back to cited text no. 94
Minegishi T, Tano M, Abe Y, Nakamura K, Ibuki Y, et al. Expression of luteinizing hormone/human chorionic gonadotrophin (LH/HCG) receptor mRNA in the human ovary. Mol Hum Reprod 1997; 3: 101-7.  Back to cited text no. 95
Messinis IE. Ovulation induction: a mini review. Hum Reprod 2005; 20: 2688-97.  Back to cited text no. 96
Hübner K, Fuhrmann G, Christenson LK, Kehler J, Reinbold R, et al. Derivation of oocytes from mouse embryonic stem cells. Science 2003; 300: 1251-6.  Back to cited text no. 97
Liu T, Huang Y, Bu Y, Zhao Y, Zou G, et al. Induction of E-cadherin+human amniotic fluid cell differentiation into oocyte-like cells via culture in medium supplemented with follicular fluid. Mol Med Rep 2014; 10: 21-8.  Back to cited text no. 98
Spradling A, Fuller MT, Braun RE, Yoshida S. Germline stem cells. Cold Spring Harb Perspect Biol 2011; 3: a002642.  Back to cited text no. 99
Lehmann R. Germline stem cells: origin and destiny. Cell Stem Cell 2012; 10: 729-39.  Back to cited text no. 100
Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 2004; 428: 145-50.  Back to cited text no. 101
White YA, Woods DC, Takai Y, Ishihara O, Seki H, et al. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med 2012; 18: 413-21.  Back to cited text no. 102
Zou K, Yuan Z, Yang Z, Luo H, Sun K, et al. Production of offspring from a germline stem cell line derived from neonatal ovaries. Nat Cell Biol 2009; 11: 631-6.  Back to cited text no. 103
Johnson J, Bagley J, Skaznik-Wikiel M, Lee HJ, Adams GB, et al. Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell 2005; 122: 303-15.  Back to cited text no. 104
Telfer EE, Gosden RG, Byskov AG, Spears N, Albertini D, et al. On regenerating the ovary and generating controversy. Cell 2005; 122: 821-2.  Back to cited text no. 105
Eggan K, Jurga S, Gosden R, Min IM, Wagers AJ. Ovulated oocytes in adult mice derive from non-circulating germ cells. Nature 2006; 441: 1109-14.  Back to cited text no. 106
Zhang H, Zheng W, Shen Y, Adhikari D, Ueno H, et al. Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries. Proc Natl Acad Sci U S A 2012; 109: 12580-5.  Back to cited text no. 107
Lei L, Spradling AC. Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles. Proc Natl Acad Sci U S A 2013; 110: 8585-90.  Back to cited text no. 108
Byskov AG, Høyer PE, Yding Andersen C, Kristensen SG, Jespersen A, et al. No evidence for the presence of oogonia in the human ovary after their final clearance during the first two years of life. Hum Reprod 2011; 26: 2129-39.  Back to cited text no. 109
de Bruin JP, Dorland M, Spek ER, Posthuma G, van Haaften M, et al. Ultrastructure of the resting ovarian follicle pool in healthy young women. Biol Reprod 2002; 66: 1151-60.  Back to cited text no. 110
Baerwald AR, Adams GP, Pierson RA. Characterization of ovarian follicular wave dynamics in women. Biol Reprod 2003; 69: 1023-31.  Back to cited text no. 111
Chen HF, Kuo HC, Chien CL, Shun CT, Yao YL, et al. Derivation, characterization and differentiation of human embryonic stem cells: comparing serum-containing versus serum-free media and evidence of germ cell differentiation. Hum Reprod 2007; 22: 567-77.  Back to cited text no. 112
West FD, Machacek DW, Boyd NL, Pandiyan K, Robbins KR, et al. Enrichment and differentiation of human germ-like cells mediated by feeder cells and basic fibroblast growth factor signaling. Stem Cells 2008; 26: 2768-76.  Back to cited text no. 113
Park TS, Galic Z, Conway AE, Lindgren A, van Handel BJ, et al. Derivation of primordial germ cells from human embryonic and induced pluripotent stem cells is significantly improved by coculture with human fetal gonadal cells. Stem Cells 2009; 27: 783-95.  Back to cited text no. 114
Aflatoonian B, Ruban L, Jones M, Aflatoonian R, Fazeli A, et al. In vitro post-meiotic germ cell development from human embryonic stem cells. Hum Reprod 2009; 24: 3150-9.  Back to cited text no. 115
West FD, Roche-Rios MI, Abraham S, Rao RR, Natrajan MS, et al. KIT ligand and bone morphogenetic protein signaling enhances human embryonic stem cell to germ-like cell differentiation. Hum Reprod 2010; 25: 168-78.  Back to cited text no. 116
Kedem A, Fisch B, Garor R, Ben-Zaken A, Gizunterman T, et al. Growth differentiating factor 9 (GDF9) and bone morphogenetic protein 15 both activate development of human primordial follicles in vitro, with seemingly more beneficial effects of GDF9. J Clin Endocrinol Metab 2011; 96: E1246-54.  Back to cited text no. 117
West FD, Mumaw JL, Gallegos-Cardenas A, Young A, Stice SL. Human haploid cells differentiated from meiotic competent clonal germ cell lines that originated from embryonic stem cells. Stem Cells Dev 2011; 20: 1079-88.  Back to cited text no. 118
Childs AJ, Kinnell HL, He J, Anderson RA. LIN28 is selectively expressed by primordial and pre-meiotic germ cells in the human fetal ovary. Stem Cells Dev 2012; 21: 2343-9.  Back to cited text no. 119
Wongtrakoongate P, Jones M, Gokhale PJ, Andrews PW. STELLA facilitates differentiation of germ cell and endodermal lineages of human embryonic stem cells. PLoS One 2013; 8: e56893.  Back to cited text no. 120

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