Expression of Stimulated by Retinoic Acid Gene 8 (Stra8) in Spermatogenic Cells Induced by Retinoic Acid: An In Vivo Study in Vitamin A-Sufficient Postnatal Murine Testes1

Zhou, Qing; Nie, Ruqiong; Liu, Ying; Friel, Patrick J.; Mitchell, Debra; Hess, Rex A.; Small, Christopher; Griswold, Michael D.

doi:10.1095/biolreprod.107.066795

Cited by 234 publications

(267 citation statements)

References 29 publications

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“…It is known that RA is an upstream regulator of KIT and STRA8 expression during the transition from undifferentiated to differentiated spermatogonia, making them convenient markers in the distinction of these two germ cell phases (Schrans-Stassen et al 1999, Zhou et al 2008a. Similarly, we have shown that RA treatment upregulates Stra8 and Kit mRNA expression in neonatal rat gonocytes (Wang & Culty 2007).…”

Section: Spermatogonia and Ssc Differentiationsupporting

confidence: 64%

“…One of these markers is stimulated by RA8 (STRA8), first identified as a target gene of RA in P19 mouse embryonal carcinoma cells, and later, in F9 mouse embryonal teratocarcinoma cells, undifferentiated spermatogonia, and premeiotic male germ cells (Bouillet et al 1995, Oulad-Abdelghani et al 1996, Giuili et al 2002, Zhou et al 2008a. Since then, the role of STRA8 as an essential initiator of meiosis in male and female germ cells has been clearly demonstrated in Stra8 knockout mice that were infertile, due to disrupted meiosis and premature chromosome condensation (Baltus et al 2006, Mark et al 2008.…”

Section: Transitional Gonocyte Differentiation In Rodentsmentioning

confidence: 99%

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Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges

Manku¹,

Culty²

2015

Reproduction

122

105

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The production of spermatozoa relies on a pool of spermatogonial stem cells (SSCs), formed in infancy from the differentiation of their precursor cells, the gonocytes. Throughout adult life, SSCs will either self-renew or differentiate, in order to maintain a stem cell reserve while providing cells to the spermatogenic cycle. By contrast, gonocytes represent a transient and finite phase of development leading to the formation of SSCs or spermatogonia of the first spermatogenic wave. Gonocyte development involves phases of quiescence, cell proliferation, migration, and differentiation. Spermatogonia, on the other hand, remain located at the basement membrane of the seminiferous tubules throughout their successive phases of proliferation and differentiation. Apoptosis is an integral part of both developmental phases, allowing for the removal of defective cells and the maintenance of proper germ-Sertoli cell ratios. While gonocytes and spermatogonia mitosis are regulated by distinct factors, they both undergo differentiation in response to retinoic acid. In contrast to postpubertal spermatogenesis, the early steps of germ cell development have only recently attracted attention, unveiling genes and pathways regulating SSC self-renewal and proliferation. Yet, less is known on the mechanisms regulating differentiation. The processes leading from gonocytes to spermatogonia have been seldom investigated. While the formation of abnormal gonocytes or SSCs could lead to infertility, defective gonocyte differentiation might be at the origin of testicular germ cell tumors. Thus, it is important to better understand the molecular mechanisms regulating these processes. This review summarizes and compares the present knowledge on the mechanisms regulating mammalian gonocyte and spermatogonial differentiation.

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Section: Spermatogonia and Ssc Differentiationsupporting

confidence: 64%

Section: Transitional Gonocyte Differentiation In Rodentsmentioning

confidence: 99%

Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges

Manku¹,

Culty²

2015

Reproduction

122

105

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“…An opportunity to explore this question experimentally arises from recent studies of Stra8 (Stimulated by retinoic acid gene 8), a vertebrate-specific gene that encodes a cytoplasmic protein and whose expression is induced by retinoic acid (6)(7)(8)(9)(10)(11). Our laboratory previously reported that, in female mice, Stra8 is expressed in embryonic ovarian germ cells shortly before they enter meiotic prophase (12).…”

mentioning

confidence: 99%

“…In male mice, Stra8 is expressed postnatally, in the mitotically active cells of the spermatogenic lineage (spermatogonia) and their immediate descendants (preleptotene spermatocytes), the most advanced cell type before meiotic prophase (6,10,14). We previously reported that male mice lacking Stra8 function produced no sperm; most spermatogenic cells underwent apoptosis at a developmental stage when they normally would have progressed through meiotic prophase (13).…”

mentioning

confidence: 99%

Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice

Anderson

Baltus²,

Roepers-Gajadien³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

534

523

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In eukaryotes, diploid cells give rise to haploid cells via meiosis, a program of two cell divisions preceded by one round of DNA replication. Although key molecular components of the meiotic apparatus are highly conserved among eukaryotes, the mechanisms responsible for initiating the meiotic program have diverged substantially among eukaryotes. This raises a related question in animals with two distinct sexes: Within a given species, are similar or different mechanisms of meiotic initiation used in the male and female germ lines? In mammals, this question is underscored by dramatic differences in the timing of meiotic initiation in males and females. Stra8 is a vertebrate-specific, cytoplasmic factor expressed by germ cells in response to retinoic acid. We previously demonstrated that Stra8 gene function is required for meiotic initiation in mouse embryonic ovaries. Here we report that, on an inbred C57BL/6 genetic background, the same factor is also required for meiotic initiation in germ cells of juvenile mouse testes. In juvenile C57BL/6 males lacking Stra8 gene function, the early mitotic development of germ cells appears to be undisturbed. However, these cells then fail to undergo the morphological changes that define meiotic prophase, and they do not display the molecular hallmarks of meiotic chromosome cohesion, synapsis and recombination. We conclude that, in mice, Stra8 regulates meiotic initiation in both spermatogenesis and oogenesis. Taken together with previous observations, our present findings indicate that, in both the male and female germ lines, meiosis is initiated through retinoic acid induction of Stra8. meiosis ͉ spermatocyte

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“…22,23 Preleptotene spermatocytes entering meiosis are characterized by their intense expression of stimulated by the retinoic acid gene 8 (Stra8), a protein indispensible for premeiotic DNA synthesis. [24][25][26] Despite these progresses, the process of early spermatogonial differentiation is still not well understood.…”

Section: Introductionmentioning

confidence: 99%

Quantitative analysis of male germline stem cell differentiation reveals a role for the p53-mTORC1 pathway in spermatogonial maintenance

et al. 2015

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Abbreviations: mTORC1, mammalian target of rapamycin complex 1; FACS, flow cytometry; GDNF, glial cell line-derived neurotrophic; Plzf, promyelocytic leukemia zinc finger; hHLH, Basic helix-loop-helix; Stra8, stimulated by the retinoic acid gene 8; p-RPS6, phosphorylated ribosomal protein S6.p53 protects cells from DNA damage by inducing cell-cycle arrest upon encountering genomic stress. Among other pathways, p53 elicits such an effect by inhibiting mammalian target of rapamycin complex 1 (mTORC1), the master regulator of cell proliferation and growth. Although recent studies have indicated roles for both p53 and mTORC1 in stem cell maintenance, it remains unclear whether the p53-mTORC1 pathway is conserved to mediate this process under normal physiological conditions. Spermatogenesis is a classic stem cell-dependent process in which undifferentiated spermatogonia undergo self-renewal and differentiation to maintain the lifelong production of spermatozoa. To better understand this process, we have developed a novel flow cytometry (FACS)-based approach that isolates spermatogonia at consecutive differentiation stages. By using this as a tool, we show that genetic loss of p53 augments mTORC1 activity during early spermatogonial differentiation. Functionally, loss of p53 drives spermatogonia out of the undifferentiated state and causes a consistent expansion of early differentiating spermatogonia until the stage of preleptotene (premeiotic) spermatocyte. The frequency of early meiotic spermatocytes is, however, dramatically decreased. Thus, these data suggest that p53-mTORC1 pathway plays a critical role in maintaining the homeostasis of early spermatogonial differentiation. Moreover, our FACS approach could be a valuable tool in understanding spermatogonial differentiation.

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Expression of Stimulated by Retinoic Acid Gene 8 (Stra8) in Spermatogenic Cells Induced by Retinoic Acid: An In Vivo Study in Vitamin A-Sufficient Postnatal Murine Testes1

Cited by 234 publications

References 29 publications

Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges

Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges

Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice

Quantitative analysis of male germline stem cell differentiation reveals a role for the p53-mTORC1 pathway in spermatogonial maintenance

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