Genetic analysis of activin/inhibin β subunits in zebrafish development and reproduction.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101239074 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7404 (Electronic) Linking ISSN: 15537390 NLM ISO Abbreviation: PLoS Genet Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, c2005-

Inhibins*/genetics ; Inhibins*/metabolism ; Inhibin-beta Subunits*/genetics ; Inhibin-beta Subunits*/metabolism; Animals ; Female ; Zebrafish/genetics ; Zebrafish/metabolism ; Activins/genetics ; Activins/metabolism ; Reproduction/genetics ; Mammals/metabolism

Activin and inhibin are both dimeric proteins sharing the same β subunits that belong to the TGF-β superfamily. They are well known for stimulating and inhibiting pituitary FSH secretion, respectively, in mammals. In addition, activin also acts as a mesoderm-inducing factor in frogs. However, their functions in development and reproduction of other species are poorly defined. In this study, we disrupted all three activin/inhibin β subunits (βAa, inhbaa; βAb, inhbab; and βB, inhbb) in zebrafish using CRISPR/Cas9. The loss of βAa/b but not βB led to a high mortality rate in the post-hatching stage. Surprisingly, the expression of fshb but not lhb in the pituitary increased in the female βA mutant together with aromatase (cyp19a1a) in the ovary. The single mutant of βAa/b showed normal folliculogenesis in young females; however, their double mutant (inhbaa-/-;inhbab-/-) showed delayed follicle activation, granulosa cell hypertrophy, stromal cell accumulation and tissue fibrosis. The ovary of inhbaa-/- deteriorated progressively after 180 dpf with reduced fecundity and the folliculogenesis ceased completely around 540 dpf. In addition, tumor- or cyst-like tissues started to appear in the inhbaa-/- ovary after about one year. In contrast to females, activin βAa/b mutant males showed normal spermatogenesis and fertility. As for activin βB subunit, the inhbb-/- mutant exhibited normal folliculogenesis, spermatogenesis and fertility in both sexes; however, the fecundity of mutant females decreased dramatically at 270 dpf with accumulation of early follicles. In summary, the activin-inhibin system plays an indispensable role in fish reproduction, in particular folliculogenesis and ovarian homeostasis.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2022 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mol Cell Endocrinol. 2002 Feb 25;188(1-2):195-205. (PMID: 11911957)
J Hazard Mater. 2020 Mar 15;386:121886. (PMID: 31887561)
Biol Reprod. 2017 Jan 1;97(6):873-882. (PMID: 29136085)
Endocrinology. 2020 Jul 1;161(7):. (PMID: 32274496)
Exp Biol Med (Maywood). 2002 Feb;227(2):75-87. (PMID: 11815670)
Dev Growth Differ. 2008 Jun;50 Suppl 1:S35-45. (PMID: 18430162)
J Clin Endocrinol Metab. 2001 May;86(5):2125-35. (PMID: 11344217)
Front Endocrinol (Lausanne). 2018 Oct 11;9:593. (PMID: 30364302)
Mol Cell Endocrinol. 2004 Oct 15;225(1-2):119-25. (PMID: 15451576)
Biol Reprod. 2004 Dec;71(6):2056-64. (PMID: 15329331)
Hum Mol Genet. 2008 Jul 15;17(14):2228-37. (PMID: 18424453)
Gen Comp Endocrinol. 2002 Jan;125(1):142-9. (PMID: 11825043)
Mol Endocrinol. 2007 Oct;21(10):2458-71. (PMID: 17609433)
Semin Reprod Med. 2004 Aug;22(3):269-76. (PMID: 15319829)
Hum Reprod. 2001 Apr;16(4):668-72. (PMID: 11278215)
J Biol Chem. 2007 Dec 14;282(50):36755-65. (PMID: 17951260)
Int J Dev Biol. 1991 Dec;35(4):407-14. (PMID: 1801866)
Biochem Biophys Res Commun. 1993 Jun 15;193(2):711-7. (PMID: 8512569)
Genes Dev. 1994 Feb 15;8(4):414-27. (PMID: 8125256)
J Clin Endocrinol Metab. 1991 Jun;72(6):1206-11. (PMID: 2026742)
Oncol Lett. 2017 Nov;14(5):5871-5875. (PMID: 29113220)
Endocrinology. 1991 Mar;128(3):1682-4. (PMID: 1900235)
Biotechniques. 2007 Nov;43(5):610, 612, 614. (PMID: 18072590)
Biol Reprod. 1999 Oct;61(4):987-92. (PMID: 10491634)
Dev Biol. 2006 Oct 1;298(1):132-48. (PMID: 16930587)
Gen Comp Endocrinol. 2003 Jun 1;132(1):142-50. (PMID: 12765654)
Cytokine Growth Factor Rev. 2013 Jun;24(3):285-95. (PMID: 23541927)
Nature. 1995 Mar 23;374(6520):354-6. (PMID: 7885473)
Gen Comp Endocrinol. 1993 Mar;89(3):333-40. (PMID: 8335224)
Nature. 1995 Mar 23;374(6520):311-2. (PMID: 7885466)
Biol Reprod. 2002 Feb;66(2):259-65. (PMID: 11804937)
Mol Cell Endocrinol. 2001 Jun 30;180(1-2):139-44. (PMID: 11451583)
Endocrinology. 2012 Dec;153(12):6065-77. (PMID: 23117933)
Proc Natl Acad Sci U S A. 1985 Nov;82(21):7217-21. (PMID: 3864157)
Cancer Cell Int. 2020 Dec 14;20(1):598. (PMID: 33317551)
Mol Cell Endocrinol. 1999 Aug 20;154(1-2):45-54. (PMID: 10509799)
J Endocrinol. 2007 Dec;195(3):373-84. (PMID: 18000300)
Gynecol Oncol. 2007 Feb;104(2):331-7. (PMID: 17064757)
Mol Cell Endocrinol. 2012 Sep 25;361(1-2):133-42. (PMID: 22503865)
Endocrinology. 2020 Dec 1;161(12):. (PMID: 33045050)
Nature. 1990 Jun 21;345(6277):729-31. (PMID: 2113615)
Gen Comp Endocrinol. 2005 Mar;141(1):22-38. (PMID: 15707600)
Neuroendocrinology. 1991 Oct;54(4):373-7. (PMID: 1758579)
Nature. 1986 Jun 19-25;321(6072):776-9. (PMID: 3012369)
Biochem Biophys Res Commun. 2019 Jan 29;509(1):175-181. (PMID: 30581008)
Nature. 1990 Jun 21;345(6277):732-4. (PMID: 2113616)
Genes Dev. 1994 Jun 15;8(12):1448-62. (PMID: 7926744)
Endocr Rev. 1988 May;9(2):267-93. (PMID: 3136011)
J Mol Endocrinol. 1997 Aug;19(1):37-45. (PMID: 9278859)
Elife. 2022 May 19;11:. (PMID: 35588359)
Gen Comp Endocrinol. 2010 Jul 1;167(3):397-407. (PMID: 19799903)
Sci Rep. 2016 Nov 23;6:37357. (PMID: 27876832)
Endocrinology. 2000 Mar;141(3):1263-72. (PMID: 10698204)
Gen Comp Endocrinol. 2005 Sep 15;143(3):287-99. (PMID: 15925369)
Dev Growth Differ. 1999 Aug;41(4):463-71. (PMID: 10466934)
Food Funct. 2016 Apr;7(4):1915-23. (PMID: 27040153)
Mol Cell Endocrinol. 2012 Aug 15;359(1-2):53-65. (PMID: 21664422)
Int J Oncol. 2001 Jun;18(6):1133-44. (PMID: 11351242)
Endocrinology. 2011 Nov;152(11):4358-67. (PMID: 21952240)
Mol Cell Endocrinol. 2004 Oct 15;225(1-2):29-36. (PMID: 15451565)
Br J Cancer. 1999 Aug;80(12):1920-6. (PMID: 10471040)
Cell. 1998 May 15;93(4):557-68. (PMID: 9604931)
Nature. 1995 Mar 23;374(6520):356-60. (PMID: 7885474)
Mol Reprod Dev. 2013 May;80(5):384-92. (PMID: 23533185)
Neuroendocrinology. 1999 Oct;70(4):246-54. (PMID: 10529619)
Nature. 1992 Nov 26;360(6402):313-9. (PMID: 1448148)
PLoS One. 2017 Jun 29;12(6):e0179789. (PMID: 28662143)
Mol Endocrinol. 1996 Apr;10(4):356-66. (PMID: 8721981)
Biol Reprod. 2011 Sep;85(3):615-25. (PMID: 21636738)
Growth Factors. 2004 Mar;22(1):13-8. (PMID: 15176454)
Gynecol Oncol. 1998 Apr;69(1):23-31. (PMID: 9570994)
Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10526-31. (PMID: 20498064)
Mol Cell Endocrinol. 2012 Aug 15;359(1-2):30-42. (PMID: 21964464)
Cold Spring Harb Perspect Biol. 2016 Jul 01;8(7):. (PMID: 27328872)
Gen Comp Endocrinol. 2009 Jan 15;160(2):183-93. (PMID: 19063890)
Gen Comp Endocrinol. 1999 Oct;116(1):81-9. (PMID: 10525364)
J Endocrinol. 1998 Feb;156(2):269-74. (PMID: 9518872)
Environ Microbiol. 2021 Sep;23(9):5258-5272. (PMID: 33973327)
Mol Endocrinol. 2005 Jan;19(1):237-54. (PMID: 15375186)
Methods Mol Biol. 2021;2218:1-9. (PMID: 33606218)
Gen Comp Endocrinol. 2012 Jan 1;175(1):82-91. (PMID: 22019479)
Nature. 1986 Jun 19-25;321(6072):779-82. (PMID: 3086749)
Mol Cell Biol. 1997 Mar;17(3):1682-91. (PMID: 9032295)
Gen Comp Endocrinol. 2004 Jan 1;135(1):108-15. (PMID: 14644650)
Mol Endocrinol. 2015 Jan;29(1):76-98. (PMID: 25396299)
Biol Reprod. 2012 Mar 19;86(3):73. (PMID: 22116804)
Endocrinology. 2003 Feb;144(2):474-83. (PMID: 12538607)
Reproduction. 2009 Oct;138(4):709-19. (PMID: 19602521)
Endocrinology. 1995 Mar;136(3):849-56. (PMID: 7867593)
Endocrinology. 1993 Dec;133(6):2554-60. (PMID: 8243277)
Mol Endocrinol. 2004 Mar;18(3):606-23. (PMID: 14701940)
Gynecol Oncol. 2005 Mar;96(3):671-7. (PMID: 15721410)
Reprod Biol Endocrinol. 2007 Jun 05;5:21. (PMID: 17550604)
J Clin Endocrinol Metab. 2014 Oct;99(10):E1922-32. (PMID: 25062451)
Nature. 1994 Oct 6;371(6497):487-92. (PMID: 7935761)
Cancer Lett. 2009 Nov 28;285(2):157-65. (PMID: 19493612)
Biol Reprod. 2003 Dec;69(6):1998-2006. (PMID: 12930712)
Endocrinology. 2015 Oct;156(10):3747-62. (PMID: 25993524)
Biol Reprod. 2022 May 17;106(5):928-942. (PMID: 35040951)
Fertil Steril. 2017 Oct;108(4):694-702. (PMID: 28863940)
Cytokine Growth Factor Rev. 2006 Jun;17(3):157-71. (PMID: 16481210)

57285-09-3 (Inhibins)
93443-12-0 (Inhibin-beta Subunits)
104625-48-1 (Activins)

Date Created: 20221205 Date Completed: 20221219 Latest Revision: 20221227

20221227

PMC9754609

10.1371/journal.pgen.1010523

36469526