Mutation of Brain Aromatase Disrupts Spawning Behavior and Reproductive Health in Female Zebrafish

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2023 Jul 12

PMID 37435485

Authors

Katherine Shaw

Mylene Therrien

Chunyu Lu

Xiaochun Liu

Vance L Trudeau

Affiliations

Soon will be listed here.

Abstract

Aromatase (Cyp19a1) is the steroidogenic enzyme that converts androgens into bioactive estrogens, and hence is in a pivotal position to mediate reproduction and sexual behavior. In teleosts, there are two aromatase paralogs: that is highly expressed in granulosa and Leydig cells in the gonads with critical function in sexual differentiation of the ovary, and that is highly expressed in radial glial cells in the brain with unknown roles in reproduction. mutant zebrafish lines were used to investigate the importance of the paralogs for spawning behavior and offspring survival and early development. Mutation of was found to increase the latency to the first oviposition in females. Mutation of in females also increased the number of eggs spawned; however, significantly more progeny died during early development resulting in no net increase in female fecundity. This finding suggests a higher metabolic cost of reproduction in mutant females. In males, the combined mutation of both paralogs resulted in significantly lower progeny survival rates, indicating a critical function of during early larval development. These data establish the specific importance of for female spawning behavior and the importance of the paralogs for early larval survival.

Citing Articles

Editorial: Steroids and the brain, volume II.

Ubuka T, Trudeau V Front Endocrinol (Lausanne). 2025; 16:1556800.

PMID: 39959620 PMC: 11825336. DOI: 10.3389/fendo.2025.1556800.

Cyp19a1a Promotes Ovarian Maturation through Regulating E2 Synthesis with in (Euphrasen, 1788).

Guo C, Zhang K, Li C, Xing R, Xu S, Wang D Int J Mol Sci. 2024; 25(3).

PMID: 38338860 PMC: 10855460. DOI: 10.3390/ijms25031583.

Simultaneous extraction and detection of peptides, steroids, and proteins in small tissue samples.

Lu C, Peng D, Erandani W, Mitchell K, Martyniuk C, Trudeau V Front Endocrinol (Lausanne). 2023; 14:1266985.

PMID: 37876537 PMC: 10593444. DOI: 10.3389/fendo.2023.1266985.

References

Converse A, Thomas P . Androgens regulate follicle stage-dependent pro- and anti-apoptosis in teleost ovaries through ZIP9 activation of different G proteins†. Biol Reprod. 2019; 101(2):377-391. DOI: 10.1093/biolre/ioz086. View

Martinez R, Navarro-Martin L, Luccarelli C, Codina A, Raldua D, Barata C . Unravelling the mechanisms of PFOS toxicity by combining morphological and transcriptomic analyses in zebrafish embryos. Sci Total Environ. 2019; 674:462-471. DOI: 10.1016/j.scitotenv.2019.04.200. View

Sawyer S, Gerstner K, Callard G . Real-time PCR analysis of cytochrome P450 aromatase expression in zebrafish: gene specific tissue distribution, sex differences, developmental programming, and estrogen regulation. Gen Comp Endocrinol. 2006; 147(2):108-17. DOI: 10.1016/j.ygcen.2005.12.010. View

Alward B, Laud V, Skalnik C, York R, Juntti S, Fernald R . Modular genetic control of social status in a cichlid fish. Proc Natl Acad Sci U S A. 2020; 117(45):28167-28174. PMC: 7668075. DOI: 10.1073/pnas.2008925117. View

Fisher C, Graves K, Parlow A, Simpson E . Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene. Proc Natl Acad Sci U S A. 1998; 95(12):6965-70. PMC: 22703. DOI: 10.1073/pnas.95.12.6965. View

Santos D, Matos M, Coimbra A . Developmental toxicity of endocrine disruptors in early life stages of zebrafish, a genetic and embryogenesis study. Neurotoxicol Teratol. 2014; 46:18-25. DOI: 10.1016/j.ntt.2014.08.002. View

Honda S, Harada N, Takagi Y . Novel exon 1 of the aromatase gene specific for aromatase transcripts in human brain. Biochem Biophys Res Commun. 1994; 198(3):1153-60. DOI: 10.1006/bbrc.1994.1163. View

Bugel S, White L, Cooper K . Decreased vitellogenin inducibility and 17β-estradiol levels correlated with reduced egg production in killifish (Fundulus heteroclitus) from Newark Bay, NJ. Aquat Toxicol. 2011; 105(1-2):1-12. PMC: 4798252. DOI: 10.1016/j.aquatox.2011.03.013. View

Hayward A, Gillooly J . The cost of sex: quantifying energetic investment in gamete production by males and females. PLoS One. 2011; 6(1):e16557. PMC: 3026017. DOI: 10.1371/journal.pone.0016557. View

10.

Oliveira R, Silva J, Simoes J . Fighting zebrafish: characterization of aggressive behavior and winner-loser effects. Zebrafish. 2011; 8(2):73-81. DOI: 10.1089/zeb.2011.0690. View

11.

Menuet A, Pellegrini E, Brion F, Gueguen M, Anglade I, Pakdel F . Expression and estrogen-dependent regulation of the zebrafish brain aromatase gene. J Comp Neurol. 2005; 485(4):304-20. DOI: 10.1002/cne.20497. View

12.

Brooks D, Coon V J, Ercan C, Xu X, Dong H, Levine J . Brain Aromatase and the Regulation of Sexual Activity in Male Mice. Endocrinology. 2020; 161(10). PMC: 7485274. DOI: 10.1210/endocr/bqaa137. View

13.

Yin Y, Tang H, Liu Y, Chen Y, Li G, Liu X . Targeted Disruption of Aromatase Reveals Dual Functions of cyp19a1a During Sex Differentiation in Zebrafish. Endocrinology. 2017; 158(9):3030-3041. DOI: 10.1210/en.2016-1865. View

14.

Nishiike Y, Miyazoe D, Togawa R, Yokoyama K, Nakasone K, Miyata M . Estrogen receptor 2b is the major determinant of sex-typical mating behavior and sexual preference in medaka. Curr Biol. 2021; 31(8):1699-1710.e6. DOI: 10.1016/j.cub.2021.01.089. View

15.

Matsumoto T, Honda S, Harada N . Alteration in sex-specific behaviors in male mice lacking the aromatase gene. Neuroendocrinology. 2003; 77(6):416-24. DOI: 10.1159/000071313. View

16.

Simpson E, Mahendroo M, Means G, Kilgore M, Hinshelwood M, Amarneh B . Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev. 1994; 15(3):342-55. DOI: 10.1210/edrv-15-3-342. View

17.

Tang H, Chen Y, Liu Y, Yin Y, Li G, Guo Y . New Insights Into the Role of Estrogens in Male Fertility Based on Findings in Aromatase-Deficient Zebrafish. Endocrinology. 2017; 158(9):3042-3054. DOI: 10.1210/en.2017-00156. View

18.

Dranow D, Hu K, Bird A, Lawry S, Adams M, Sanchez A . Bmp15 Is an Oocyte-Produced Signal Required for Maintenance of the Adult Female Sexual Phenotype in Zebrafish. PLoS Genet. 2016; 12(9):e1006323. PMC: 5028036. DOI: 10.1371/journal.pgen.1006323. View

19.

Huffman L, OConnell L, Hofmann H . Aromatase regulates aggression in the African cichlid fish Astatotilapia burtoni. Physiol Behav. 2013; 112-113:77-83. DOI: 10.1016/j.physbeh.2013.02.004. View

20.

Darrow K, Harris W . Characterization and development of courtship in zebrafish, Danio rerio. Zebrafish. 2008; 1(1):40-5. DOI: 10.1089/154585404774101662. View