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Article ; Online: Synchronizing spermatogenesis in the mouse.

Griswold, Michael / Hogarth, Cathryn

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: Beyond stem cells: Commitment of progenitor cells to meiosis.

Griswold, Michael D / Hogarth, Cathryn

Stem cell research

2018 Volume 27, Page(s) 169–171

Abstract: The first step in established spermatogenesis is the production of progenitor cells by the stem cell population. The progenitor cells (undifferentiated A spermatogonia) expand in number via the formation of syncytial chains by mitosis. The mechanism by ... ...

Abstract	The first step in established spermatogenesis is the production of progenitor cells by the stem cell population. The progenitor cells (undifferentiated A spermatogonia) expand in number via the formation of syncytial chains by mitosis. The mechanism by which these progenitor cells commit to meiosis and spermatogenesis is tightly controlled and results in complex morphological organization all of which is designed to efficiently achieve large numbers of spermatozoa. The major extrinsic factor that triggers the commitment to meiosis and establishes the structural complexity is retinoic acid (RA). Retinoic acid is produced from retinol via two oxidation steps in low abundance near its site of action. The action of RA on undifferentiated A spermatogonia results in the timed progression of these progenitor cells into the cycle of the seminiferous epithelium. We have utilized a drug WIN 18,446 that inhibits the second oxidation step in RA biosynthesis to block the progression of undifferentiated A spermatogonia in the mouse testis. As a result of this block the undifferentiated progenitor cells accumulate but do not differentiate into A1 spermatogonia. When the block is released and a bolus of RA is simultaneously administered the accumulated spermatogonia progress through the differentiation pathway in complete synchrony and maintain that synchrony with regard to stages of the cycle of the seminiferous epithelium for several months. This procedure allowed us to accumulate sufficient material to measure retinoic acid levels across the cycle and will allow us to isolate and analyze large number of progenitor cells proceeding synchronously down the pathway to meiosis. We have been able to show that the cycle of the seminiferous epithelium is established and maintained by pulses of RA that appear at stages VIII and IX of the cycle.
MeSH term(s)	Animals ; Male ; Meiosis/genetics ; Meiosis/physiology ; Mice ; Spermatogenesis/genetics ; Spermatogenesis/physiology ; Stem Cells/cytology ; Stem Cells/metabolism ; Tretinoin/metabolism
Chemical Substances	Tretinoin (5688UTC01R)
Language	English
Publishing date	2018-01-31
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1876-7753
ISSN (online)	1876-7753
DOI	10.1016/j.scr.2018.01.032
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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: Crucial Convolution: Genetic and Molecular Mechanisms of Coiling during Epididymis Formation and Development in Embryogenesis

Wong, Joanne / Gasperoni, Jemma / Fuller, Jarrad / Grommen, Sylvia V. H. / De Groef, Bert / Hogarth, Cathryn / Dworkin, Sebastian

Journal of developmental biology. 2022 June 14, v. 10, no. 2

2022

Abstract: As embryonic development proceeds, numerous organs need to coil, bend or fold in order to establish their final shape. Generally, this occurs so as to maximise the surface area for absorption or secretory functions (e.g., in the small and large ... ...

Abstract	As embryonic development proceeds, numerous organs need to coil, bend or fold in order to establish their final shape. Generally, this occurs so as to maximise the surface area for absorption or secretory functions (e.g., in the small and large intestines, kidney or epididymis); however, mechanisms of bending and shaping also occur in other structures, notably the midbrain–hindbrain boundary in some teleost fish models such as zebrafish. In this review, we will examine known genetic and molecular factors that operate to pattern complex, coiled structures, with a primary focus on the epididymis as an excellent model organ to examine coiling. We will also discuss genetic mechanisms involving coiling in the seminiferous tubules and intestine to establish the final form and function of these coiled structures in the mature organism.
Keywords	Danio rerio ; absorption ; embryogenesis ; epididymis ; fish ; intestines ; kidneys ; surface area
Language	English
Dates of publication	2022-0614
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720870-9
ISSN	2221-3759
ISSN	2221-3759
DOI	10.3390/jdb10020025
Database	NAL-Catalogue (AGRICOLA)

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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: Crucial Convolution: Genetic and Molecular Mechanisms of Coiling during Epididymis Formation and Development in Embryogenesis.

Wong, Joanne / Gasperoni, Jemma / Fuller, Jarrad / Grommen, Sylvia V H / De Groef, Bert / Hogarth, Cathryn / Dworkin, Sebastian

Journal of developmental biology

2022 Volume 10, Issue 2

Abstract	As embryonic development proceeds, numerous organs need to coil, bend or fold in order to establish their final shape. Generally, this occurs so as to maximise the surface area for absorption or secretory functions (e.g., in the small and large intestines, kidney or epididymis); however, mechanisms of bending and shaping also occur in other structures, notably the midbrain-hindbrain boundary in some teleost fish models such as zebrafish. In this review, we will examine known genetic and molecular factors that operate to pattern complex, coiled structures, with a primary focus on the epididymis as an excellent model organ to examine coiling. We will also discuss genetic mechanisms involving coiling in the seminiferous tubules and intestine to establish the final form and function of these coiled structures in the mature organism.
Language	English
Publishing date	2022-06-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720870-9
ISSN	2221-3759 ; 2221-3759
ISSN (online)	2221-3759
ISSN	2221-3759
DOI	10.3390/jdb10020025
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Article ; Online: Differential localization of histone variant TH2B during the first round compared with subsequent rounds of spermatogenesis.

Beedle, My-Thanh / Topping, Traci / Hogarth, Cathryn / Griswold, Michael

Developmental dynamics : an official publication of the American Association of Anatomists

2019 Volume 248, Issue 6, Page(s) 488–500

Abstract: Background: Male germ cells are unique because they express a substantial number of variants of the general DNA binding proteins, known as histones, yet the biological significance of these variants is still unknown. In the present study, we aimed to ... ...

Abstract	Background: Male germ cells are unique because they express a substantial number of variants of the general DNA binding proteins, known as histones, yet the biological significance of these variants is still unknown. In the present study, we aimed to address the expression pattern of the testis-specific histone H2B variant (TH2B) and the testis-specific histone H2A variant (TH2A) within the neonatal mouse testis. Results: We demonstrate that TH2B and TH2A are present in a testis-enriched for undifferentiated spermatogonia. Co-localization studies with an undifferentiated marker, ZBTB16, revealed that TH2B and ZBTB16 co-localize in the neonatal testis. Upon the appearance of the primary spermatocytes, TH2B no longer co-localized with the ZBTB16 positive spermatogonia but were instead detected within the differentiating spermatogonia. This pattern of expression where TH2B and ZBTB16 no longer co-localize was maintained in the adult testis. Conclusion: These findings are in contrast to previous studies, which demonstrated that TH2B and TH2A were found only in adult spermatocytes. Our data are in support of a switch in the expression of these variants following the first round of spermatogonial differentiation. These studies reinforce current understandings that spermatogonia within the neonatal mouse testis are inherently different from those residing within the adult testis.
MeSH term(s)	Animals ; Animals, Newborn ; Genetic Variation ; Histones/analysis ; Histones/genetics ; Male ; Mice ; Spermatocytes/chemistry ; Spermatogenesis ; Testis/chemistry
Chemical Substances	Histones ; histone H2B type 1-A
Language	English
Publishing date	2019-04-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1102541-4
ISSN	1097-0177 ; 1058-8388
ISSN (online)	1097-0177
ISSN	1058-8388
DOI	10.1002/dvdy.33
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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: 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: Inhibition of the

Stevison, Faith / Hogarth, Cathryn / Tripathy, Sasmita / Kent, Travis / Isoherranen, Nina

Drug metabolism and disposition: the biological fate of chemicals

2017 Volume 45, Issue 7, Page(s) 846–854

Abstract: ... All- ... ...

Abstract	All-trans
MeSH term(s)	Animals ; Benzothiazoles/pharmacokinetics ; Benzothiazoles/pharmacology ; Cytochrome P-450 Enzyme Inhibitors/pharmacokinetics ; Cytochrome P-450 Enzyme Inhibitors/pharmacology ; Dose-Response Relationship, Drug ; Gene Expression/drug effects ; Liver/metabolism ; Male ; Mice, Inbred C57BL ; Organ Specificity ; Protein Binding ; Retinoic Acid 4-Hydroxylase/antagonists & inhibitors ; Signal Transduction ; Testis/metabolism ; Tretinoin/blood ; Tretinoin/metabolism ; Triazoles/pharmacokinetics ; Triazoles/pharmacology
Chemical Substances	Benzothiazoles ; Cytochrome P-450 Enzyme Inhibitors ; Triazoles ; Tretinoin (5688UTC01R) ; Cyp26a1 protein, mouse (EC 1.14.14.1) ; Cyp26b1 protein, mouse (EC 1.14.14.1) ; Retinoic Acid 4-Hydroxylase (EC 1.14.14.1) ; R 115866 (XKD9N5CJ6W)
Language	English
Publishing date	2017-04-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	186795-7
ISSN	1521-009X ; 0090-9556
ISSN (online)	1521-009X
ISSN	0090-9556
DOI	10.1124/dmd.117.075341
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