NELF knockout is associated with impaired pubertal development and subfertility

Molecular and Cellular Endocrinology
Samuel D QuaynorLawrence C Layman

Abstract

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. Th...Continue Reading

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Citations

Dec 25, 2015·Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology·Katherine E KaugarsPaul D Heideman
Nov 3, 2016·Rare Diseases·Christina SpilkerMichael R Kreutz
Jun 21, 2019·The Journal of Clinical Endocrinology and Metabolism·Andrew A DwyerRavikumar Balasubramanian
Jul 30, 2019·Frontiers in Cell and Developmental Biology·Hyun-Ju ChoSusan Wray
Jun 2, 2021·Molecular and Cellular Endocrinology·Erica D LoudenLawrence C Layman

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