{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:29:22Z","timestamp":1790674162788,"version":"4.1.0"},"reference-count":70,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Vertebrate reproduction is controlled by two gonadotropins (FSH and LH) from the pituitary. Despite numerous studies on FSH and LH in fish species, their functions in reproduction still remain poorly defined. This is partly due to the lack of powerful genetic approaches for functional studies in adult fish. This situation is now changing with the emergence of genome-editing technologies, especially Transcription Activator-Like Effector Nuclease (TALEN) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR). In this study, we deleted the hormone-specific \u03b2-genes of both FSH and LH in the zebrafish using TALEN. This was followed by a phenotype analysis for key reproductive events, including gonadal differentiation, puberty onset, gametogenesis, final maturation, and fertility. FSH-deficient zebrafish (fshb\u2212\/\u2212) were surprisingly fertile in both sexes; however, the development of both the ovary and testis was significantly delayed. In contrast, LH-deficient zebrafish (lhb\u2212\/\u2212) showed normal gonadal growth, but the females failed to spawn and were therefore infertile. Using previtellogenic follicles as the marker, we observed a significant delay of puberty onset in the fshb mutant but not the lhb mutant females. Interestingly, FSH seemed to play a role in maintaining the female status because we repeatedly observed sexual reversal in the fshb mutant. Neither the fshb nor lhb mutation alone seemed to affect gonadal differentiation; however, the double mutation of the two genes led to all males, although the development of the testis was significantly delayed. In summary, our data confirmed some well-known functions of FSH and LH in fish while also providing evidence for novel functions, which would be difficult to reveal using traditional biochemical and physiological approaches.<\/jats:p>","DOI":"10.1210\/me.2014-1256","type":"journal-article","created":{"date-parts":[[2014,11,14]],"date-time":"2014-11-14T18:38:27Z","timestamp":1415990307000},"page":"76-98","source":"Crossref","is-referenced-by-count":235,"title":["Genetic Analysis of Zebrafish Gonadotropin (FSH and LH) Functions by TALEN-Mediated Gene Disruption"],"prefix":"10.1210","volume":"29","author":[{"given":"Zhiwei","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Life Sciences (Z.Z., B.Z., W.G.), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China"},{"name":"Faculty of Health Sciences (Z.Z., W.G.), University of Macau, Taipa, Macau, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhu","sequence":"first","affiliation":[{"name":"School of Life Sciences (Z.Z., B.Z., W.G.), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ge","sequence":"first","affiliation":[{"name":"School of Life Sciences (Z.Z., B.Z., W.G.), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China"},{"name":"Faculty of Health Sciences (Z.Z., W.G.), University of Macau, Taipa, Macau, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613050014700_B1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1210\/edrv-11-1-177","article-title":"Molecular biology of the pituitary gonadotropins","volume":"11","author":"Gharib","year":"1990","journal-title":"Endocr Rev"},{"key":"2020071613050014700_B2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1530\/reprod\/119.2.173","article-title":"The Parkes Lecture. Mutations of gonadotrophin and gonadotrophin receptor genes: what do they teach us about reproductive physiology?","volume":"119","author":"Huhtaniemi","year":"2000","journal-title":"J Reprod Fertil"},{"key":"2020071613050014700_B3","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1210\/edrv.21.5.0409","article-title":"Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function","volume":"21","author":"Themmen","year":"2000","journal-title":"Endocr Rev"},{"key":"2020071613050014700_B4","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/ng0297-201","article-title":"Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility","volume":"15","author":"Kumar","year":"1997","journal-title":"Nat Genet"},{"key":"2020071613050014700_B5","doi-asserted-by":"crossref","first-page":"17294","DOI":"10.1073\/pnas.0404743101","article-title":"Targeted disruption of luteinizing hormone \u03b2-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and infertility","volume":"101","author":"Ma","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613050014700_B6","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1152\/ajplegacy.1931.97.2.291","article-title":"The gonad stimulating and the luteinizing hormone of the anterior lobe of the hypophysis","volume":"97","author":"Fevold","year":"1931","journal-title":"Am J Physiol"},{"key":"2020071613050014700_B7","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1139\/f82-010","article-title":"Chemical data on pituitary gonadotropins and their implication to evolution","volume":"39","author":"Burzawa-Gerard","year":"1982","journal-title":"Can J Fish Aquat Sci"},{"key":"2020071613050014700_B8","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1093\/icb\/13.3.909","article-title":"Reproductive endocrinology of fishes","volume":"73","author":"Donaldson","year":"1973","journal-title":"Am Zool"},{"key":"2020071613050014700_B9","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/0016-6480(72)90201-8","article-title":"The gonadotropins of lower vertebrates","volume":"3","author":"Burzawa-Gerard","year":"1972","journal-title":"Gen Comp Endocrinol"},{"key":"2020071613050014700_B10","first-page":"187","article-title":"Teleost gonadotropins: isolation, biochemistry, and function","volume-title":"Fish Physiology","author":"Idler","year":"1983"},{"key":"2020071613050014700_B11","doi-asserted-by":"crossref","first-page":"237","DOI":"10.3109\/07435807509053851","article-title":"Fish gonadotropin(s). III. Evidence for more than one gonadotropin in chum salmon pituitary glands","volume":"2","author":"Idler","year":"1975","journal-title":"Endocr Res Commun"},{"key":"2020071613050014700_B12","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/0016-6480(79)90150-3","article-title":"Studies on two types of gonadotropins from both salmon and carp pituitaries","volume":"38","author":"Idler","year":"1979","journal-title":"Gen Comp Endocrinol"},{"key":"2020071613050014700_B13","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.tibtech.2013.04.004","article-title":"ZFN, TALEN, and CRISPR\/Cas-based methods for genome engineering","volume":"31","author":"Gaj","year":"2013","journal-title":"Trends Biotechnol"},{"key":"2020071613050014700_B14","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/0016-6480(88)90258-4","article-title":"Isolation and characterization of subunits from two distinct salmon gonadotropins","volume":"71","author":"Suzuki","year":"1988","journal-title":"Gen Comp Endocrinol"},{"key":"2020071613050014700_B15","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1677\/joe.0.1560529","article-title":"A comprehensive evolutionary analysis based on nucleotide and amino acid sequences of the \u03b1- and \u03b2-subunits of glycoprotein hormone gene family","volume":"156","author":"Li","year":"1998","journal-title":"J Endocrinol"},{"key":"2020071613050014700_B16","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1095\/biolreprod63.1.222","article-title":"Phylogenetic analysis of the vertebrate glycoprotein hormone family including new sequences of sturgeon (Acipenser baeri) \u03b2 subunits of the two gonadotropins and the thyroid-stimulating hormone","volume":"63","author":"Querat","year":"2000","journal-title":"Biol 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