ArticleEndocrinology2014
Heterozygous deletion of ventral anterior homeobox (vax1) causes subfertility in mice.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Haploinsufficiency of Sox2 causes fewer GnRH neurons and delayed puberty in mice.Endocrinology · 2026Article
- The transcription factor VAX1 in VIP neurons of the suprachiasmatic nucleus impacts circadian rhythm generation, depressive-like behavior, and the reproductive axis in a sex-specific manner in mice.Frontiers in endocrinology · 2023Article
- Homeodomain protein HOMEZ is dispensable for male fertility in mice.Translational andrology and urology · 2022Article
- Mouse Cre drivers: tools for studying disorders of the human female neuroendocrine-reproductive axis†.Biology of reproduction · 2022Review
- Deletion of the homeodomain gene Six3 from kisspeptin neurons causes subfertility in female mice.Molecular and cellular endocrinology · 2022Article
- Circadian Rhythms in the Neuronal Network Timing the Luteinizing Hormone Surge.Endocrinology · 2022Review
- Case report: A heterozygous mutation inFrontiers in genetics · 2022Article
- The transcription factors SIX3 and VAX1 are required for suprachiasmatic nucleus circadian output and fertility in female mice.Journal of neuroscience research · 2021Article
- Kiss1 is differentially regulated in male and female mice by the homeodomain transcription factor VAX1.Molecular and cellular endocrinology · 2021Article
- Transcription Factor VAX1 Regulates the Regional Specification of the Subpallium Through Repressing Gsx2.Molecular neurobiology · 2021Article
- Article
- Discovering candidate imprinted genes and imprinting control regions in the human genome.BMC genomics · 2020Article
- Role of core circadian clock genes in hormone release and target tissue sensitivity in the reproductive axis.Molecular and cellular endocrinology · 2020Review
- The Homeodomain Transcription Factors Vax1 and Six6 Are Required for SCN Development and Function.Molecular neurobiology · 2020Article
- Deletion of the Homeodomain Protein Six6 From GnRH Neurons Decreases GnRH Gene Expression, Resulting in Infertility.Endocrinology · 2019Article
- Haploinsufficiency of Homeodomain Proteins Six3, Vax1, and Otx2 Causes Subfertility in Mice via Distinct Mechanisms.Neuroendocrinology · 2019Review
- Differential CRE Expression in Lhrh-cre and GnRH-cre Alleles and the Impact on Fertility in Otx2-Flox Mice.Neuroendocrinology · 2019Article
- Haploinsufficiency of SIX3 Abolishes Male Reproductive Behavior Through Disrupted Olfactory Development, and Impairs Female Fertility Through Disrupted GnRH Neuron Migration.Molecular neurobiology · 2018Article
- Determination of Reproductive Competence by Confirming Pubertal Onset and Performing a Fertility Assay in Mice and Rats.Journal of visualized experiments : JoVE · 2018Article
- Transcriptional interaction between cFOS and the homeodomain-binding transcription factor VAX1 on the GnRH promoter controls Gnrh1 expression levels in a GnRH neuron maturation specific manner.Molecular and cellular endocrinology · 2018Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The known genetic causes of idiopathic hypogonadotropic hypogonadism (IHH) are often associated with the loss of GnRH neurons, leading to the disruption of the hypothalamic pituitary gonadal axis and subfertility. The majority of IHH cases have unknown origins and likely arise from compound mutations in more than one gene. Here we identify the homeodomain transcription factor ventral anterior homeobox1 (Vax1) as a potential genetic contributor to polygenic IHH. Although otherwise healthy, male and female Vax1 heterozygous (HET) mice are subfertile, indicating dosage sensitivity for the Vax1 allele. Although Vax1 mRNA is expressed in the pituitary, hypothalamus, and testis, we did not detect Vax1 mRNA in the sperm, ovary, or isolated pituitary gonadotropes. Whereas Vax1 HET females produced normal numbers of superovulated oocytes, corpora lutea numbers were reduced along with a slight increase in circulating basal LH and estrogen. The subfertility originated in the hypothalamus in which kisspeptin and GnRH transcripts were altered along with a substantial reduction of GnRH neuron number. Although the pituitary responded normally to a GnRH challenge, diestrus females had reduced LHβ and FSHβ in diestrus. Furthermore, Vax1 HET males had reduced GnRH mRNA and neuron numbers, whereas the pituitary had normal transcript levels and response to GnRH. Interestingly, the Vax1 HET males had an 88% reduction of motile sperm. Taken together, our data suggest that Vax1 HET subfertility originates in the hypothalamus by disrupting the hypothalamic-pituitary-gonadal axis. In addition, male subfertility may also be due to an unknown effect of Vax1 in the testis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.