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Article: Transcriptional/translational regulation of mammalian spermatogenic stem cells.

Hogarth, Cathryn A

Advances in experimental medicine and biology

2013 Volume 786, Page(s) 105–128

MeSH term(s)	Animals ; Cell Differentiation ; Cell Proliferation ; Epigenesis, Genetic ; Gene Expression Regulation, Developmental ; Humans ; Intercellular Signaling Peptides and Proteins/genetics ; Intercellular Signaling Peptides and Proteins/metabolism ; Male ; Mammals/genetics ; Mammals/growth & development ; Mammals/metabolism ; Protein Biosynthesis ; Signal Transduction ; Spermatocytes/cytology ; Spermatocytes/metabolism ; Spermatogonia/cytology ; Spermatogonia/metabolism ; Stem Cells/cytology ; Stem Cells/metabolism ; Transcription, Genetic
Chemical Substances	Intercellular Signaling Peptides and Proteins
Language	English
Publishing date	2013
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-94-007-6621-1_7
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Article: Germ Cell Commitment to Oogenic Versus Spermatogenic Pathway: The Role of Retinoic Acid.

Agrimson, Kellie S / Hogarth, Cathryn A

Results and problems in cell differentiation

2016 Volume 58, Page(s) 135–166

Abstract: The core of the decision to commit to either oogenesis or spermatogenesis lies in the timing of meiotic entry. Primordial germ cells within the fetal ovary become committed to the female pathway prior to birth and enter meiosis during embryonic ... ...

Abstract	The core of the decision to commit to either oogenesis or spermatogenesis lies in the timing of meiotic entry. Primordial germ cells within the fetal ovary become committed to the female pathway prior to birth and enter meiosis during embryonic development. In the fetal testis, however, the germ cells are protected from this signal before birth and instead receive this trigger postnatally. There is a growing body of evidence to indicate that RA is the meiosis-inducing factor in both sexes, with the gender-specific timing of meiotic entry controlled via degradation of this molecule only within the fetal testis. This chapter will review our current understanding of how RA controls germ cell fate in both the embryonic ovary and postnatal testis, highlighting the key studies that have led to the hypothesis that RA can drive the commitment to meiosis in both sexes and discussing the current debate over whether RA truly is the meiosis-inducing factor in the fetal ovary.
MeSH term(s)	Animals ; Female ; Gene Expression Regulation, Developmental ; Germ Cells/cytology ; Germ Cells/metabolism ; Humans ; Male ; Oogenesis/genetics ; Oogenesis/physiology ; Signal Transduction/genetics ; Signal Transduction/physiology ; Spermatogenesis/genetics ; Spermatogenesis/physiology ; Tretinoin/metabolism ; Tretinoin/physiology
Chemical Substances	Tretinoin (5688UTC01R)
Language	English
Publishing date	2016
Publishing country	Germany
Document type	Journal Article ; Review
ISSN	0080-1844
ISSN	0080-1844
DOI	10.1007/978-3-319-31973-5_6
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Article ; Online: Immunohistochemical approaches for the study of spermatogenesis.

Hogarth, Cathryn A / Griswold, Michael D

Methods in molecular biology (Clifton, N.J.)

2013 Volume 927, Page(s) 309–320

Abstract: Immunohistochemistry is an important technique that uses specific antibodies to determine the cellular localization of proteins/antigens in highly complex organs and tissues. While most immunohistochemistry experiments target protein epitopes, nonprotein ...

Abstract	Immunohistochemistry is an important technique that uses specific antibodies to determine the cellular localization of proteins/antigens in highly complex organs and tissues. While most immunohistochemistry experiments target protein epitopes, nonprotein antigens including BrdU may also be detected. Briefly, tissues are fixed, processed, sectioned, and then probed by a primary antibody while preserving the integrity of the tissue and cellular morphology. There are various methods available for visualization of the bound primary antibody that involve a reporter molecule which can be detected using light or fluorescent microscopy. Here we describe a basic immunohistochemistry protocol for identifying protein localization in testis sections using protein-specific antibodies.
MeSH term(s)	Antibodies/immunology ; Antibodies/metabolism ; Humans ; Immunohistochemistry/methods ; Male ; Spermatogenesis/physiology ; Testis/immunology ; Testis/metabolism
Chemical Substances	Antibodies
Language	English
Publishing date	2013
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-62703-038-0_28
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Article ; Online: Retinoic acid regulation of male meiosis.

Hogarth, Cathryn A / Griswold, Michael D

Current opinion in endocrinology, diabetes, and obesity

2013 Volume 20, Issue 3, Page(s) 217–223

Abstract: Purpose of review: Description of new evidence to support the model for how retinoic acid regulates spermatogonial differentiation, male meiosis and the cycle of the seminiferous epithelium.: Recent findings: It has been known since the 1920s that ... ...

Abstract	Purpose of review: Description of new evidence to support the model for how retinoic acid regulates spermatogonial differentiation, male meiosis and the cycle of the seminiferous epithelium. Recent findings: It has been known since the 1920s that vitamin A is essential for spermatogenesis. However, only recently has significant progress been made toward understanding how the active metabolite of vitamin A, retinoic acid, regulates spermatogenesis at multiple different differentiation steps, including the onset of meiosis. Current publications suggest that the initiation and maintenance of the cycle of the seminiferous epithelium is linked to retinoic-acid-driving spermatogonial differentiation and meiotic onset. Summary: Retinoic acid appears to act in a pulsatile manner, periodically driving spermatogonial differentiation and meiotic onset at discrete points along testis tubules, and as a result, is likely to be responsible for generating and maintaining the cycle of the seminiferous epithelium.
MeSH term(s)	Animals ; Humans ; Male ; Meiosis ; Models, Biological ; Receptors, Retinoic Acid/metabolism ; Seminiferous Epithelium/cytology ; Seminiferous Epithelium/growth & development ; Seminiferous Epithelium/metabolism ; Signal Transduction ; Spermatogenesis ; Spermatozoa/cytology ; Spermatozoa/metabolism ; Tretinoin/metabolism
Chemical Substances	Receptors, Retinoic Acid ; Tretinoin (5688UTC01R)
Language	English
Publishing date	2013-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2272017-0
ISSN	1752-2978 ; 1752-296X
ISSN (online)	1752-2978
ISSN	1752-296X
DOI	10.1097/MED.0b013e32836067cf
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Article ; Online: Synchronizing spermatogenesis in the mouse.

Griswold, Michael / Hogarth, Cathryn

Biology of reproduction

2022 Volume 107, Issue 5, Page(s) 1159–1165

Abstract: The formation of spermatozoa starts with a germ-line stem cell creating a pool of progenitor cells or undifferentiated spermatogonia. There is a requirement for these progenitor cells to be stimulated by retinoic acid (RA) to enter differentiation and ... ...

Abstract	The formation of spermatozoa starts with a germ-line stem cell creating a pool of progenitor cells or undifferentiated spermatogonia. There is a requirement for these progenitor cells to be stimulated by retinoic acid (RA) to enter differentiation and ultimately form spermatocytes, undergo meiosis, form spermatids, and ultimately spermatozoa. After the stimulation by RA, which occurs at sites in the seminiferous tubules, it takes ~35 days to complete this complex process. As a result, the adult testis contains germ cells in all possible states of differentiation, and the isolation of individual cell types or study of functional aspects of the cycle of the seminiferous epithelium is very difficult. We describe the use of WIN 18 446-an inhibitor of RA synthesis followed by injection of RA as a mechanism for the synchronization of spermatogenesis to one to three stages of the cycle of the seminiferous epithelium. The result is that only one to four germ cell types are prevalent during the first wave of spermatogenesis. In the adult only a predictable few stages of the cycle are present throughout the entire testis enriching the targeted cells or stages of the cycle.
MeSH term(s)	Male ; Mice ; Animals ; Spermatogenesis/physiology ; Spermatogonia ; Testis/metabolism ; Spermatids/metabolism ; Spermatozoa/metabolism ; Tretinoin/pharmacology ; Tretinoin/metabolism ; Meiosis ; Sertoli Cells/metabolism
Chemical Substances	Tretinoin (5688UTC01R)
Language	English
Publishing date	2022-07-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1118-6
ISSN	1529-7268 ; 0006-3363
ISSN (online)	1529-7268
ISSN	0006-3363
DOI	10.1093/biolre/ioac148
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Article ; Online: Retinoic acid receptor signaling is necessary in steroidogenic cells for normal spermatogenesis and epididymal function.

Jauregui, Estela J / Mitchell, Debra / Topping, Traci / Hogarth, Cathryn A / Griswold, Michael D

Development (Cambridge, England)

2018 Volume 145, Issue 13

Abstract: Spermatogenesis in mammals is a very complex, highly organized process, regulated in part by testosterone and retinoic acid (RA). Much is known about how RA and testosterone signaling pathways independently regulate this process, but there is almost no ... ...

Abstract	Spermatogenesis in mammals is a very complex, highly organized process, regulated in part by testosterone and retinoic acid (RA). Much is known about how RA and testosterone signaling pathways independently regulate this process, but there is almost no information regarding whether these two signaling pathways directly interact and whether RA is crucial for steroidogenic cell function. This study uses a transgenic mouse line that expresses a dominant-negative form of RA receptor α (RAR-DN) and the steroidogenic cell-specific Cre mouse line,
MeSH term(s)	Animals ; Blood-Testis Barrier/cytology ; Blood-Testis Barrier/metabolism ; Fertility/physiology ; Male ; Mice ; Mice, Transgenic ; Retinoic Acid Receptor alpha/genetics ; Retinoic Acid Receptor alpha/metabolism ; Signal Transduction/physiology ; Spermatocytes/cytology ; Spermatocytes/metabolism ; Spermatogenesis/physiology ; Steroid 17-alpha-Hydroxylase/genetics ; Steroid 17-alpha-Hydroxylase/metabolism
Chemical Substances	Rara protein, mouse ; Retinoic Acid Receptor alpha ; Steroid 17-alpha-Hydroxylase (EC 1.14.14.19)
Language	English
Publishing date	2018-07-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	90607-4
ISSN	1477-9129 ; 0950-1991
ISSN (online)	1477-9129
ISSN	0950-1991
DOI	10.1242/dev.160465
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Article ; Online: Leydig cell genes change their expression and association with polysomes in a stage-specific manner in the adult mouse testis.

Jauregui, Estela J / Mitchell, Debra / Garza, Savanna M / Topping, Traci / Hogarth, Cathryn A / Griswold, Michael D

Biology of reproduction

2018 Volume 98, Issue 5, Page(s) 722–738

Abstract: Spermatogenesis in mammals occurs in a very highly organized manner within the seminiferous epithelium regulated by different cell types in the testis. Testosterone produced by Leydig cells regulates blood-testis barrier formation, meiosis, ... ...

Abstract	Spermatogenesis in mammals occurs in a very highly organized manner within the seminiferous epithelium regulated by different cell types in the testis. Testosterone produced by Leydig cells regulates blood-testis barrier formation, meiosis, spermiogenesis, and spermiation. However, it is unknown whether Leydig cell function changes with the different stages of the seminiferous epithelium. This study utilized the WIN 18,446 and retinoic acid (RA) treatment regime combined with the RiboTag mouse methodology to synchronize male germ cell development and allow for the in vivo mapping of the Leydig cell translatome across the different stages of one cycle of the seminiferous epithelium. Using microarrays analysis, we identified 11 Leydig cell-enriched genes that were expressed in stage-specific manner such as the glucocorticoid synthesis and transport genes, Cyp21a1 and Serpina6. In addition, there were nine Leydig cell transcripts that change their association with polysomes in correlation with the different stages of the spermatogenic cycle including Egr1. Interestingly, the signal intensity of EGR1 and CYP21 varied among Leydig cells in the adult asynchronous testis. However, testosterone levels across the different stages of germ cell development did not cycle. These data show, for the first time, that Leydig cell gene expression changes in a stage-specific manner during the cycle of the seminiferous epithelium and indicate that a heterogeneous Leydig cell population exists in the adult mouse testis.
MeSH term(s)	Animals ; Blood-Testis Barrier ; Gene Expression ; Leydig Cells/cytology ; Leydig Cells/metabolism ; Male ; Mice ; Polyribosomes/metabolism ; Seminiferous Epithelium/cytology ; Seminiferous Epithelium/metabolism ; Spermatogenesis/physiology ; Steroid 21-Hydroxylase/genetics ; Steroid 21-Hydroxylase/metabolism ; Testis/cytology ; Testis/metabolism ; Transcortin/genetics ; Transcortin/metabolism
Chemical Substances	Serpina6 protein, mouse ; Transcortin (9010-38-2) ; Cyp21a1 protein, mouse (EC 1.14.14.16) ; Steroid 21-Hydroxylase (EC 1.14.14.16)
Language	English
Publishing date	2018-02-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1118-6
ISSN	1529-7268 ; 0006-3363
ISSN (online)	1529-7268
ISSN	0006-3363
DOI	10.1093/biolre/ioy031
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Article ; Online: The key role of vitamin A in spermatogenesis.

Hogarth, Cathryn A / Griswold, Michael D

The Journal of clinical investigation

2010 Volume 120, Issue 4, Page(s) 956–962

Abstract: Spermatogenesis in adult mammals is highly organized, with the goal being continual sperm production. Vertebrate testes are arranged into recurring cellular associations that vary with time and distance along the tubule. These changes over time and ... ...

Abstract	Spermatogenesis in adult mammals is highly organized, with the goal being continual sperm production. Vertebrate testes are arranged into recurring cellular associations that vary with time and distance along the tubule. These changes over time and distance are designated the cycle of the seminiferous epithelium and the spermatogenic wave, respectively. In this Review, we briefly outline the roles that follicle-stimulating hormone (FSH) and testosterone play in regulating spermatogenesis and describe our current understanding of how vitamin A regulates germ cell differentiation and how it may lead to the generation of both the cycle of the seminiferous epithelium and the spermatogenic wave.
MeSH term(s)	Animals ; Cell Differentiation ; Follicle Stimulating Hormone/physiology ; Humans ; Male ; Meiosis ; Seminiferous Epithelium/physiology ; Sertoli Cells/physiology ; Spermatogenesis/physiology ; Testosterone/physiology ; Vitamin A/physiology
Chemical Substances	Vitamin A (11103-57-4) ; Testosterone (3XMK78S47O) ; Follicle Stimulating Hormone (9002-68-0)
Language	English
Publishing date	2010-04-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI41303
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Article ; Online: Dynamic paraspeckle component localisation during spermatogenesis.

Major, Andrew T / Hogarth, Cathryn A / Young, Julia C / Kurihara, Yasuyuki / Jans, David A / Loveland, Kate L

Reproduction (Cambridge, England)

2019 Volume 158, Issue 3, Page(s) 267–280

Abstract: Expression profiles and subcellular localisations of core Drosophila behaviour/human splicing (DBHS) proteins (PSPC1, SFPQ and NONO) and NEAT1, a long noncoding RNA (lncRNA), are investigated in developing and adult mouse testes. Core DBHS proteins are ... ...

Abstract	Expression profiles and subcellular localisations of core Drosophila behaviour/human splicing (DBHS) proteins (PSPC1, SFPQ and NONO) and NEAT1, a long noncoding RNA (lncRNA), are investigated in developing and adult mouse testes. Core DBHS proteins are markers for the distinct subnuclear domain termed paraspeckles, while a long NEAT1 isoform scaffold facilitates paraspeckle nucleation. Paraspeckles contain many proteins (>40) and are broadly involved in RNA metabolism, including transcriptional regulation by protein sequestration, nuclear retention of A-to-I edited RNA transcripts to regulate translation and promoting survival during cellular stress. Immunohistochemistry reveals cell-specific profiles for core DBHS paraspeckle protein expression, indicating their functional diversity. PSPC1 is an androgen receptor co-activator, and it is detected in differentiating Sertoli cell nuclei from day 15 onwards, as they develop androgen responsiveness. PSPC1 is nuclear in the most mature male germ cell type present at each age, from foetal to adult life. In adult mouse testes, PSPC1 and SFPQ are present in Sertoli cells, spermatocytes and round spermatids, while the NEAT1 lncRNA appears in the punctate nuclear foci delineating paraspeckles only within Leydig cells. Identification of NEAT1 in the cytoplasm of spermatogonia and spermatocytes must reflect non-paraspeckle-related functions. NONO was absent from germ cells but nuclear in Sertoli cells. Reciprocal nuclear profiles of PSPC1 and γ-H2AX in spermatogenic cells suggest that each performs developmentally regulated roles in stress responses. These findings demonstrate paraspeckles and paraspeckle-related proteins contribute to diverse functions during testis development and spermatogenesis.
MeSH term(s)	Animals ; Cell Line ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Gene Expression Regulation ; Leydig Cells/metabolism ; Male ; Mice ; PTB-Associated Splicing Factor/genetics ; PTB-Associated Splicing Factor/metabolism ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Sertoli Cells/metabolism ; Spermatogenesis/physiology ; Testis/growth & development ; Testis/metabolism
Chemical Substances	DNA-Binding Proteins ; NEAT1 long non-coding RNA, mouse ; Nono protein, mouse ; PTB-Associated Splicing Factor ; RNA, Long Noncoding ; RNA-Binding Proteins ; paraspeckle protein 1, mouse
Language	English
Publishing date	2019-07-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2034501-X
ISSN	1741-7899 ; 1470-1626 ; 1476-3990
ISSN (online)	1741-7899
ISSN	1470-1626 ; 1476-3990
DOI	10.1530/REP-19-0139
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Article ; Online: Inhibiting vitamin A metabolism as an approach to male contraception.

Hogarth, Cathryn A / Amory, John K / Griswold, Michael D

Trends in endocrinology and metabolism: TEM

2011 Volume 22, Issue 4, Page(s) 136–144

Abstract: Although oral contraceptives have been available to women since the 1960s, contraceptive options for men have remained limited. Spermatogenesis relies on the active metabolite of vitamin A, retinoic acid, to drive spermatogonial differentiation and to ... ...

Abstract	Although oral contraceptives have been available to women since the 1960s, contraceptive options for men have remained limited. Spermatogenesis relies on the active metabolite of vitamin A, retinoic acid, to drive spermatogonial differentiation and to allow the production of normal numbers of sperm. Recent evidence describes how the enzymes which control vitamin A metabolism in the testis could be targeted to generate effective male contraceptives; however, the detailed mechanism(s) regarding how vitamin A regulates normal spermatogenesis are still unknown. The essential nature of vitamin A to male germ cell development and the prospects of developing the proteins responsible for the generation, transport, and storage of retinoic acid as targets for male contraceptive development are discussed in this review.
MeSH term(s)	Contraceptive Agents, Male/metabolism ; Humans ; Male ; Spermatogenesis/physiology ; Testis/enzymology ; Testis/metabolism ; Vitamin A/metabolism
Chemical Substances	Contraceptive Agents, Male ; Vitamin A (11103-57-4)
Language	English
Publishing date	2011-02-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1042384-9
ISSN	1879-3061 ; 1043-2760
ISSN (online)	1879-3061
ISSN	1043-2760
DOI	10.1016/j.tem.2011.01.001
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