Disruption of Zebrafish Follicle-Stimulating Hormone Receptor (fshr) But Not Luteinizing Hormone Receptor (lhcgr) Gene by TALEN Leads to Failed Follicle Activation in Females Followed by Sexual Reversal to Males

Endocrinology - Tập 156 Số 10 - Trang 3747-3762 - 2015
Zhiwei Zhang1,2, Shuk-Wa Lau1, Lingling Zhang1, Wei Ge1,2
1Centre of Reproduction, Development and Aging (Z.Z., W.G.), Faculty of Health Sciences, University of Macau, Taipa, Macau China
2School of Life Sciences (Z.Z., S.-W.L., L.Z., W.G.), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China

Tóm tắt

Gonadotropins are primary hormones that control vertebrate reproduction. In a recent study, we analyzed the impacts of FSH and LH on zebrafish reproduction by disrupting FSH and LH-β genes (fshb and lhb) using transcription activator-like effector nuclease (TALEN) technology. Using the same approach, we successfully deleted FSH and LH receptor genes (fshr and lhcgr) in the present study. In contrast to the deficiency of its cognate ligand FSH, the fshr-deficient females showed a complete failure of follicle activation with all ovarian follicles arrested at the primary growth-previtellogenic transition, which is the marker for puberty onset in females. Interestingly, after blockade at the primary growth stage for varying times, all females reversed to males, and all these males were fertile. In fshr-deficient males, spermatogenesis was normal in adults, but the initiation of spermatogenesis in juveniles was retarded. In contrast to fshr, the deletion of the lhcgr gene alone caused no obvious phenotypes in both males and females; however, double mutation of fshr and lhcgr resulted in infertile males. In summary, our results in the present study showed that Fshr was indispensable to folliculogenesis and the disruption of the fshr gene resulted in a complete failure of follicle activation followed by masculinization into males. In contrast, lhcgr does not seem to be essential to zebrafish reproduction in both males and females. Neither Fshr nor Lhcgr deficiency could phenocopy the deficiency of their cognate ligands FSH and LH, which is likely due to the fact that Fshr can be activated by both FSH and LH in the zebrafish.

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Tài liệu tham khảo

Gharib, 1990, Molecular biology of the pituitary gonadotropins, Endocr Rev, 11, 177, 10.1210/edrv-11-1-177

Catt, 1991, Reproductive Endocrinology, 3rd ed, 105

Boime, 2004, Yen and Jaffe's Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management, 75

Kumar, 1997, Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility, Nat Genet, 15, 201, 10.1038/ng0297-201

Abel, 2000, The effect of a null mutation in the follicle-stimulating hormone receptor gene on mouse reproduction, Endocrinology, 141, 1795, 10.1210/endo.141.5.7456

Krishnamurthy, 2001, Delay in sexual maturity of the follicle-stimulating hormone receptor knockout male mouse, Biol Reprod, 65, 522, 10.1095/biolreprod65.2.522

Kumar, 2001, Molecular biology of channel catfish gonadotropin receptors: 1. Cloning of a functional luteinizing hormone receptor and preovulatory induction of gene expression, Biol Reprod, 64, 1010, 10.1095/biolreprod64.3.1010

Ma, 2004, Targeted disruption of luteinizing hormone β-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and infertility, Proc Natl Acad Sci USA, 101, 17294, 10.1073/pnas.0404743101

Kanamori, 1988, Developmental changes in the properties of gonadotropin receptors in the ovarian follicles of amago salmon (Oncorhynchus rhodurus) during oogenesis, Gen Comp Endocrinol, 72, 25, 10.1016/0016-6480(88)90177-3

Kanamori, 1987, Gonadotropin receptors in the postovulatory ovary of amago salmon (Oncorhynchus rhodurus), Gen Comp Endocrinol, 66, 210, 10.1016/0016-6480(87)90269-3

Breton, 1986, Gonadotropin hormone (GtH) receptors in the ovary of the brown trout Salmo trutta L. in vitro studies, Gen Comp Endocrinol, 64, 163, 10.1016/0016-6480(86)90001-8

Le Gac, 1988, Gonadotropic hormone (GtH) receptors in the testis of the trout Salmo gairdneri: in vitro studies, Fish Physiol Biochem, 5, 209, 10.1007/BF01874798

Swanson, 1997, Advances in Comparative Endocrinology, 841

Miwa, 1994, Localization of two gonadotropin receptors in the salmon gonad by in vitro ligand autoradiography, Biol Reprod, 50, 629, 10.1095/biolreprod50.3.629

Yan, 1992, A two-receptor model for salmon gonadotropins (GTH I and GTH II), Biol Reprod, 47, 418, 10.1095/biolreprod47.3.418

Oba, 1999, The duality of fish gonadotropin receptors: cloning and functional characterization of a second gonadotropin receptor cDNA expressed in the ovary and testis of amago salmon (Oncorhynchus rhodurus), Biochem Biophys Res Commun, 265, 366, 10.1006/bbrc.1999.1700

Oba, 1999, Cloning, functional characterization, and expression of a gonadotropin receptor cDNA in the ovary and testis of amago salmon (Oncorhynchus rhodurus), Biochem Biophys Res Commun, 263, 584, 10.1006/bbrc.1999.1346

Santos, 2001, Follicle-stimulating hormone and its α and β subunits in rainbow trout (Oncorhynchus mykiss): purification, characterization, development of specific radioimmunoassays, and their seasonal plasma and pituitary concentrations in females, Biol Reprod, 65, 288, 10.1095/biolreprod65.1.288

Govoroun, 1998, Immunological cross-reactivity between rainbow trout GTH I and GTH II and their α and β subunits: application to the development of specific radioimmunoassays, Gen Comp Endocrinol, 111, 28, 10.1006/gcen.1998.7087

Kamei, 2005, Purification of follicle-stimulating hormone from immature Japanese eel, Anguilla japonica, and its biochemical properties and steroidogenic activities, Gen Comp Endocrinol, 143, 257, 10.1016/j.ygcen.2005.03.009

Vischer, 2003, Both recombinant African catfish LH and FSH are able to activate the African catfish FSH receptor, J Mol Endocrinol, 31, 133, 10.1677/jme.0.0310133

Moles, 2008, Purification and characterization of follicle-stimulating hormone from pituitary glands of sea bass (Dicentrarchus labrax), Gen Comp Endocrinol, 158, 68, 10.1016/j.ygcen.2008.05.005

Kwok, 2005, Zebrafish gonadotropins and their receptors: I. Cloning and characterization of zebrafish follicle-stimulating hormone and luteinizing hormone receptors—evidence for their distinct functions in follicle development, Biol Reprod, 72, 1370, 10.1095/biolreprod.104.038190

So, 2005, Zebrafish gonadotropins and their receptors: II. Cloning and characterization of zebrafish follicle-stimulating hormone and luteinizing hormone subunits—their spatial-temporal expression patterns and receptor specificity, Biol Reprod, 72, 1382, 10.1095/biolreprod.104.038216

Rocha, 2007, Molecular characterization of two sea bass gonadotropin receptors: cDNA cloning, expression analysis, and functional activity, Mol Cell Endocrinol, 272, 63, 10.1016/j.mce.2007.04.007

Jeng, 2007, Differential expression and regulation of gonadotropins and their receptors in the Japanese eel,, Anguilla japonica. Gen Comp Endocrinol, 154, 161, 10.1016/j.ygcen.2007.05.026

Kumar, 2001, Molecular biology of the channel catfish gonadotropin receptors: 2. Complementary DNA cloning, functional expression, and seasonal gene expression of the follicle-stimulating hormone receptor, Biol Reprod, 65, 710, 10.1095/biolreprod65.3.710

Ogiwara, 2013, Characterization of luteinizing hormone and luteinizing hormone receptor and their indispensable role in the ovulatory process of the medaka, PLoS One, 8, e54482, 10.1371/journal.pone.0054482

Tse, 2010, Spatial localization of EGF family ligands and receptors in the zebrafish ovarian follicle and their expression profiles during folliculogenesis, Gen Comp Endocrinol, 167, 397, 10.1016/j.ygcen.2009.09.012

Zhou, 2011, Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors in the zebrafish ovary: evidence for potentially dual roles of PACAP in controlling final oocyte maturation, Biol Reprod, 85, 615, 10.1095/biolreprod.111.091884

Swanson, 1991, Proceedings of the Fourth International Symposium on the Reproductive Physiology of Fish, 2

Swanson, 2003, Biochemistry and physiology of fish gonadotropins, Fish Physiol Biochem, 28, 53, 10.1023/B:FISH.0000030476.73360.07

Schulz, 2001, Gonadotropins, their receptors, and the regulation of testicular functions in fish, Comp Biochem Physiol B, 129, 407, 10.1016/S1096-4959(01)00339-6

Garcia-Lopez, 2009, Leydig cells express follicle-stimulating hormone receptors in African catfish, Endocrinology, 150, 357, 10.1210/en.2008-0447

Garcia-Lopez, 2010, Studies in zebrafish reveal unusual cellular expression patterns of gonadotropin receptor messenger ribonucleic acids in the testis and unexpected functional differentiation of the gonadotropins, Endocrinology, 151, 2349, 10.1210/en.2009-1227

Ohta, 2007, Follicle-stimulating hormone induces spermatogenesis mediated by androgen production in Japanese eel, Anguilla japonica, Biol Reprod, 77, 970, 10.1095/biolreprod.107.062299

Chauvigne, 2014, Germ-line activation of the luteinizing hormone receptor directly drives spermiogenesis in a nonmammalian vertebrate, Proc Natl Acad Sci USA, 111, 1427, 10.1073/pnas.1317838111

Huhtaniemi, 2002, Transgenic and knockout mouse models for the study of luteinizing hormone and luteinizing hormone receptor function, Mol Cell Endocrinol, 187, 49, 10.1016/S0303-7207(01)00698-0

Zhang, 2001, Normal prenatal but arrested postnatal sexual development of luteinizing hormone receptor knockout (LuRKO) mice, Mol Endocrinol, 15, 172, 10.1210/mend.15.1.0582

Huhtaniemi, 2000, Mutations of gonadotrophin and gonadotrophin receptor genes: what do they teach us about reproductive physiology?, J Reprod Fertil, 119, 173, 10.1530/reprod/119.2.173

Salvi, 2010, Kallmann Syndrome and Hypogonadotropic Hypogonadism, 1

Themmen, 2000, Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function, Endocr Rev, 21, 551, 10.1210/edrv.21.5.0409

Auer, 2014, CRISPR/Cas9 and TALEN-mediated knock-in approaches in zebrafish, Methods, 69, 142, 10.1016/j.ymeth.2014.03.027

Gaj, 2013, ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering, Trends Biotechnol, 31, 397, 10.1016/j.tibtech.2013.04.004

Wei, 2013, TALEN or Cas9—rapid, efficient and specific choices for genome modifications, J Genet Genomics, 40, 281, 10.1016/j.jgg.2013.03.013

Wright, 2014, TALEN-mediated genome editing: prospects and perspectives, Biochem J, 462, 15, 10.1042/BJ20140295

Hwang, 2013, Efficient genome editing in zebrafish using a CRISPR-Cas system, Nat Biotechnol, 31, 227, 10.1038/nbt.2501

Zhang, 2014, Genetic analysis of zebrafish gonadotropin (FSH and LH) functions by TALEN-mediated gene disruption, Mol Endocrinol, 29, 76, 10.1210/me.2014-1256

Cermak, 2011, Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting, Nucleic Acids Res, 39, e82, 10.1093/nar/gkr218

Dahlem, 2012, Simple methods for generating and detecting locus-specific mutations induced with TALENs in the zebrafish genome, PLoS Genet, 8, e1002861, 10.1371/journal.pgen.1002861

Meeker, 2007, Method for isolation of PCR-ready genomic DNA from zebrafish tissues, Biotechniques, 43, 610, 10.2144/000112619

Ota, 2013, Efficient identification of TALEN-mediated genome modifications using heteroduplex mobility assays, Genes Cells, 18, 450, 10.1111/gtc.12050

Chung, 2013, Human chorionic gonadotropin (hCG) induces MAPK3/1 phosphorylation in the zebrafish ovarian follicle cells independent of EGF/EGFR pathway, Gen Comp Endocrinol, 188, 251, 10.1016/j.ygcen.2013.04.020

Maack, 2003, Morphological development of the gonads in zebrafish, J Fish Biol, 62, 895, 10.1046/j.1095-8649.2003.00074.x

Chen, 2012, Ontogenic expression profiles of gonadotropins (fshb and lhb) and growth hormone (gh) during sexual differentiation and puberty onset in female zebrafish, Biol Reprod, 86, 73, 10.1095/biolreprod.111.094730

Chen, 2013, Gonad differentiation and puberty onset in the zebrafish: evidence for the dependence of puberty onset on body growth but not age in females, Mol Reprod Dev, 80, 384, 10.1002/mrd.22172

Ge, 2010, Recent Advances in Fish Reproduction Biology, 141

Dierich, 1998, Impairing follicle-stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance, Proc Natl Acad Sci USA, 95, 13612, 10.1073/pnas.95.23.13612

Murozumi, 2014, Loss of follicle-stimulating hormone receptor function causes masculinization and suppression of ovarian development in genetically female medaka, Endocrinology, 155, 3136, 10.1210/en.2013-2060

Takatsu, 2013, Induction of female-to-male sex change in adult zebrafish by aromatase inhibitor treatment, Sci Rep, 3, 3400, 10.1038/srep03400

Uchida, 2004, An aromatase inhibitor or high water temperature induce oocyte apoptosis and depletion of P450 aromatase activity in the gonads of genetic female zebrafish during sex-reversal, Comp Biochem Physiol A Mol Integr Physiol, 137, 11, 10.1016/S1095-6433(03)00178-8

Wang, 2007, Foxl2 up-regulates aromatase gene transcription in a female-specific manner by binding to the promoter as well as interacting with Ad4 binding protein/steroidogenic factor 1, Mol Endocrinol, 21, 712, 10.1210/me.2006-0248

Rodriguez-Mari, 2005, Characterization and expression pattern of zebrafish anti-Mullerian hormone (Amh) relative to sox9a, sox9b, and cyp19a1a, during gonad development, Gene Expr Patterns, 5, 655, 10.1016/j.modgep.2005.02.008

Sun, 2013, Sox9-related signaling controls zebrafish juvenile ovary-testis transformation, Cell Death Dis, 4, e930, 10.1038/cddis.2013.456

Wang, 2007, Anti-Mullerian hormone and 11β-hydroxylase show reciprocal expression to that of aromatase in the transforming gonad of zebrafish males, Dev Dyn, 236, 1329, 10.1002/dvdy.21129

Liu, 2007, Growth differentiation factor 9 and its spatiotemporal expression and regulation in the zebrafish ovary, Biol Reprod, 76, 294, 10.1095/biolreprod.106.054668

Chu, 2014, Targeted gene disruption in zebrafish reveals noncanonical functions of LH signaling in reproduction, Mol Endocrinol, 28, 1785, 10.1210/me.2014-1061

Toledo, 1996, An inactivating mutation of the luteinizing hormone receptor causes amenorrhea in a 46,XX female, J Clin Endocrinol Metab, 81, 3850

Wu, 1998, Inactivation of the luteinizing hormone/chorionic gonadotropin receptor by an insertional mutation in Leydig cell hypoplasia, Mol Endocrinol, 12, 1651, 10.1210/mend.12.11.0189

Bogerd, 2001, Discrepancy between molecular structure and ligand selectivity of a testicular follicle-stimulating hormone receptor of the African catfish (Clarias gariepinus), Biol Reprod, 64, 1633, 10.1095/biolreprod64.6.1633

Vischer, 2003, Cloning and functional characterization of a gonadal luteinizing hormone receptor complementary DNA from the African catfish (Clarias gariepinus), Biol Reprod, 68, 262, 10.1095/biolreprod.102.004515

Aittomaki, 1995, Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure, Cell, 82, 959, 10.1016/0092-8674(95)90275-9

Tapanainen, 1998, Inactivating FSH receptor mutations and gonadal dysfunction, Mol Cell Endocrinol, 145, 129, 10.1016/S0303-7207(98)00179-8

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Endocrinology

Tập 156 Số 10

3747-3762

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