Retinoic Acid Antagonizes Testis Development in Mice

Bowles, Josephine; Feng, Chunliang; Ineson, Jessica; Miles, Kim; Spiller, Cassy M.; Harley, Vincent R.; Sinclair, Andrew H.; Koopman, Peter

doi:10.1016/j.celrep.2018.06.111

Cited by 54 publications

(51 citation statements)

References 83 publications

(117 reference statements)

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“…Because both an excess and lack of RA are detrimental for most tissues, regulation of its concentration by CYP26 enzymes needs to be appropriately controlled (56)(57)(58)(59)(60). In the seminiferous epithelium, the major CYP26 enzyme that hydrolyzes RA is CYP26B1 (18,32).…”

Section: Discussionmentioning

confidence: 99%

“…However, despite its importance for RA degradation in the testis, the molecular control of spatiotemporal CYP26B1 expression is still poorly understood. In the male embryonic gonad, RA is synthesized by Sertoli cells but is readily degraded by CYP26B1 in order to maintain proper testis development and prospermatogonia in an undifferentiated state (58). However, induction of the spermatogenetic program shortly after birth absolutely requires RA (61-63), therefore implying down-regulation of CYP26B1 production.…”

Section: Discussionmentioning

confidence: 99%

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Undifferentiated spermatogonia regulateCyp26b1expression through NOTCH signaling and drive germ cell differentiation

et al. 2019

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Cytochrome P450 family 26 subfamily B member 1 (CYP26B1) regulates the concentration of all–trans retinoic acid (RA) and plays a key role in germ cell differentiation by controlling local distribution of RA. The mechanisms regulating Cyp26b1 expression in postnatal Sertoli cells, the main components of the stem cell niche, are so far unknown. During gonad development, expression of Cyp26b1 is maintained by Steroidogenic Factor 1 (SF‐1) and Sex‐Determining Region Y. Box‐9 (SOX9), which ensure that RA is degraded and germ cell differentiation is blocked. Here, we show that the NOTCH target Hairy/Enhancer‐of‐Split Related with YRPW Motif 1 (HEY1), a transcriptional repressor, regulates germ cell differentiation via direct binding to the Cyp26b1 promoter and thus inhibits its expression in Sertoli cells. Further, using in vivo germ cell ablation, we demonstrate that undifferentiated type A spermatogonia are the cells that activate NOTCH signaling in Sertoli cells through their expression of the NOTCH ligand JAGGED‐1 (JAG1) at stage VIII of the seminiferous epithelium cycle, therefore mediating germ cell differentiation by a ligand concentration‐dependent process. These data therefore provide more insights into the mechanisms of germ cell differentiation after birth and potentially explain the spatiotemporal RA pulses driving the transition between undifferentiated to differentiating spermatogonia.—Parekh, P. A., Garcia, T. X., Waheeb, R., Jain, V., Gandhi, P., Meistrich, M. L., Shetty, G., Hofmann, M.‐C. Undifferentiated spermatogonia regulate Cyp26b1 expression through NOTCH signaling and drive germ cell differentiation. FASEB J. 33, 8423–8435 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Undifferentiated spermatogonia regulateCyp26b1expression through NOTCH signaling and drive germ cell differentiation

et al. 2019

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“…A recent study has attempted to address this issue, and results indicate that such an effect is independent of germ cells (Bowles et al, 2018). Whether the impairment of somatic development is associated with or independent of RA action on germ cells?…”

Section: Future Directionsmentioning

confidence: 99%

“…How are the germ cells in the fetal testis protected from the effects of RA? RA-metabolizing enzyme CYCP26B1 is highly expressed in the somatic cells of testis (Bowles et al, 2018). CYP26B1 degrades RA reaching into the testis from the surrounding tissues (mainly mesonephros), thus protecting germ cells from RA exposure and subsequent meiosis.…”

Section: Suppression Of Germ Cell Proliferation and Meiosis In Fetamentioning

confidence: 99%

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Retinoic acid signaling in regulation of meiosis during embryonic development in mice

Yadu

Kumar

2019

Genesis

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Summary In the embryonic gonads of mice, the genetic and epigenetic regulatory programs for germ cell sex specification and meiosis induction or suppression are intertwined. The quest for garnering comprehensive understanding of these programs has led to the emergence of retinoic acid (RA) as an important extrinsic factor, which regulates initiation of meiosis in female fetal germ cells that have attained a permissive epigenetic ground state. In contrast, germ cells in fetal testis are protected from the exposure to RA due to the activity of CYP26B1, an RA metabolizing enzyme, which is highly expressed in fetal testis. In this review, we provide an overview of the molecular mechanisms operating in fetal gonads of mice, which enable regulation of meiosis via RA signaling.

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Formation of the rete testis during mouse embryonic development

Kulibin

Малолина

2020

Developmental Dynamics

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Background: The rete testis connects seminiferous tubules of the testis with efferent ducts having a mesonephric origin. The development of the rete testis is insufficiently studied, but there is evidence suggesting that it originates from gonadal cells. Here, the formation of the rete testis was investigated from E11.5 to E16.5 using immunofluorescent staining and 3D-modeling. Results: The rete testis became visible by SOX9 and PAX8 staining starting from E12.5. It was located in the mesonephros but connected with testis cords formed by Sertoli cells expressing SOX9, AMH, DMRT1. Between E13.5 and E14.5, AMH+ network of testis cords at the mesonephric side began to disintegrate in a gradient-dependent manner along the anterior-posterior axis of the gonad and connections between testis cords gradually lost AMH becoming a part of the rete. Cells combining features of Sertoli and rete cells (PAX8+ AMH+ and DMRT1+ AMH− cells) were detected starting from E14.5, suggesting that some rete cells originated from Sertoli cells. The rete ovarii, a female counterpart of the rete testis, developed in a similar way as the rete testis until E13.5. Conclusions: A part of the rete testis originates from connections between testis cords. Evidence that Sertoli cells contribute to rete cells is provided.

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Retinoic Acid Antagonizes Testis Development in Mice

Cited by 54 publications

References 83 publications

Undifferentiated spermatogonia regulateCyp26b1expression through NOTCH signaling and drive germ cell differentiation

Undifferentiated spermatogonia regulateCyp26b1expression through NOTCH signaling and drive germ cell differentiation

Retinoic acid signaling in regulation of meiosis during embryonic development in mice

Formation of the rete testis during mouse embryonic development

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