title: Targeted gene disruption in zebrafish reveals noncanonical functions of LH signaling in reproduction.
abstract: The pivotal role of gonadotropin signaling in regulating gonadal development and functions has attracted much research attention in the past 2 decades. However, the precise physiological role of gonadotropin signaling is still largely unknown in fish. In this study, we have established both LH β-subunit (lhb) and LH receptor (lhr) knockout zebrafish lines by transcription activator-like effector nucleases. Intriguingly, both homozygous lhb and lhr mutant male fish are fertile. The fertilization rate, sperm motility, and histological structure of the testis were not affected in either lhb or lhr mutant males. On the contrary, homozygous lhb mutant females are infertile, whereas homozygous lhr mutant females are fertile. Folliculogenesis was not affected in either lhb or lhr mutants, but oocyte maturation and ovulation were disrupted in lhb mutant, whereas only ovulation was affected in lhr mutant. Differential expression of genes in the ovary involved in steroidogenesis, oocyte maturation, and ovulation was found between the lhb and lhr mutants. These data demonstrate the essential role of LH signaling in oocyte maturation and ovulation, and support the notion that LH acts through the FSH receptor in the absence of LH receptor. Moreover, the defects of lhb mutant could be partially restored by administration of human chorionic gonadotropin. This in vivo evidence in the present study demonstrates, for the first time in any vertebrate species, that LH signaling is indispensable in female reproduction but not in male reproduction. LH signaling is demonstrated to control oocyte maturation and ovulation in the ovary.
authors.affiliation: School of Biomedical Sciences (L.C., J.L., Y.L., C.H.K.C.), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; College of Life Sciences (J.L.), Northwest Normal University, Lanzhou, China; and State Key Laboratory of Freshwater Ecology and Biotechnology (W.H.), Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Lianhe
authors.initials: L
authors.lastname: Chu
authors.forename: Jianzhen
authors.initials: J
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Christopher H K
authors.initials: CH
authors.lastname: Cheng
mesh_terms: D000818:Animals; D005260:Female; D005306:Fertilization / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation / Q000235:genetics; D006080:Ovarian Follicle / Q000378:metabolism; D010060:Ovulation / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011962:Receptors, FSH / Q000378:metabolism; D011974:Receptors, LH / Q000378:metabolism; D012098:Reproduction / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013081:Sperm Motility / Q000235:genetics / Q000502:physiology; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D037101:Luteinizing Hormone, beta Subunit; D011962:Receptors, FSH; D011974:Receptors, LH; D029961:Zebrafish Proteins