PGE2 inhibits spermatogonia differentiation in zebrafish: interaction with Fsh and an androgen

in Journal of Endocrinology
Authors:
Diego Crespo Reproductive Biology Group, Division Developmental Biology, Department Biology, Science Faculty, Utrecht University, Utrecht, The Netherlands

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Moline Severino Lemos Laboratory of Cell Biology, Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

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Yu Ting Zhang State Key Laboratory of Marine Environmental Science, College of Ocean and Earth Sciences, Xiamen University, Fujian, People’s Republic of China
Institute of Oceanography, Minjiang University, Fuzhou, People’s Republic of China

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Diego Safian Reproductive Biology Group, Division Developmental Biology, Department Biology, Science Faculty, Utrecht University, Utrecht, The Netherlands

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Birgitta Norberg Institute of Marine Research, Austevoll Research Station, Storebø, Norway

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Jan Bogerd Reproductive Biology Group, Division Developmental Biology, Department Biology, Science Faculty, Utrecht University, Utrecht, The Netherlands

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Rüdiger W Schulz Reproductive Biology Group, Division Developmental Biology, Department Biology, Science Faculty, Utrecht University, Utrecht, The Netherlands
Research Group Reproduction and Developmental Biology, Institute of Marine Research, Bergen, Norway

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Correspondence should be addressed to R W Schulz: r.w.schulz@uu.nl
DOI:
https://doi.org/10.1530/JOE-19-0309
Volume/Issue:
Volume 244: Issue 1
Article Type:
Research Article
Page Range:
163–175
Online Publication Date:
Jan 2020
Copyright:
© 2020 Society for Endocrinology 2020
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Changes in zebrafish testicular gene expression induced by follicle-stimulating hormone (Fsh) or anti-Mullerian hormone (Amh) suggested that Amh inhibition and Fsh stimulation of spermatogenesis involved up and downregulation, respectively, of prostaglandin (PG) signaling. We found that Sertoli cells contacting type A undifferentiated (Aund) and differentiating (Adiff) spermatogonia expressed a key enzyme of PG production (Ptgs2); previous work showed that Sertoli cells contacting Adiff and B spermatogonia and spermatocytes showed ptges3b expression, an enzyme catalyzing PGE2 production. In primary testis tissue cultures, PGE2, but not PGD2 or PGF2α, reduced the mitotic activity of Adiff and their development into B spermatogonia. Vice versa, inhibiting PG production increased the mitotic activity of Adiff and B spermatogonia. Studies with pharmacological PG receptor antagonists suggest that an Ep4 receptor mediates the inhibitory effects on the development of spermatogonia, and cell-sorting experiments indicated this receptor is expressed mainly by testicular somatic cells. Combined inhibition of PG and steroid production moreover reduced the mitotic activity of Aund spermatogonia and led to their partial depletion, suggesting that androgens (and/or other testicular steroids), supported by PGE2, otherwise prevent depletion of Aund. Androgens also decreased testicular PGE2 production, increased the transcript levels of the enzyme-catabolizing PGs and decreased PGE2 receptor ptger4b transcript levels. Also Fsh potentially reduced, independent of androgens, PGE2 production by decreasing ptges3b transcript levels. Taken together, our results indicate that PGE2, via Ep4 receptors, favors self-renewal in conjunction with androgens and, independent of Fsh and androgens, inhibits differentiating divisions of spermatogonia.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2020 Society for Endocrinology 2020
Page(s):
13
Article Type:
Research Article
Received Date:
03 Oct 2019
Accepted Date:
10 Oct 2019
Print Publication Date:
01 Jan 2020
Online Publication Date:
Jan 2020
Keywords:
Fsh; androgen; prostaglandin E2; spermatogonia; proliferation; differentiation; zebrafish

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