NELF knockout is associated with impaired pubertal development and subfertility
| Autor: | Eunkyung Ko, Durkadin Demir, Lawrence C. Layman, Megan E. Sullivan, Samuel D. Quaynor, Richard S. Cameron, Jennifer L. Waller, Hyung Goo Kim, Lynn P. Chorich |
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| Rok vydání: | 2014 |
| Předmět: |
Delayed puberty
Male medicine.medical_specialty endocrine system Hypothalamo-Hypophyseal System Litter Size Cell Count Biology medicine.disease_cause Biochemistry Article Gonadotropin-Releasing Hormone Mice Endocrinology Estrus Hypogonadotropic hypogonadism Cell Movement Internal medicine medicine Animals Humans Sexual Maturation Molecular Biology GnRH Neuron Mice Knockout Neurons Mutation Reproduction Homozygote Uterus NASAL EMBRYONIC LHRH FACTOR medicine.disease Phenotype Gene Expression Regulation Hypothalamus Infertility Female medicine.symptom Hormone Signal Transduction Transcription Factors |
| Zdroj: | Molecular and cellular endocrinology. 407 |
| ISSN: | 1872-8057 |
| Popis: | Puberty and reproduction require proper signaling of the hypothalamic-pituitary-gonadal axis controlled by gonadotropin-releasing hormone (GnRH) neurons, which arise in the olfactory placode region and migrate along olfactory axons to the hypothalamus. Factors adversely affecting GnRH neuron specification, migration, and function lead to delayed puberty and infertility. Nasal embryonic luteinizing hormone-releasing factor (NELF) is a predominantly nuclear protein. NELF mutations have been demonstrated in patients with hypogonadotropic hypogonadism, but biallelic mutations are rare and heterozygous NELF mutations typically co-exist with mutations in another gene. Our previous studies in immortalized GnRH neurons supported a role for NELF in GnRH neuron migration. To better understand the physiology of NELF, a homozygous Nelf knockout (KO) mouse model was generated. Our findings indicate that female Nelf KO mice have delayed vaginal opening but no delay in time to first estrus, decreased uterine weight, and reduced GnRH neuron number. In contrast, male mice were normal at puberty. Both sexes of mice had impaired fertility manifested as reduced mean litter size. These data support that NELF has important reproductive functions. The milder than expected phenotype of KO mice also recapitulates the human phenotype since heterozygous NELF mutations usually require an additional mutation in a second gene to result in hypogonadotropic hypogonadism. |
| Databáze: | OpenAIRE |
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