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Comment |
Cited2 protein level in cumulus cells is a biomarker for human embryo quality and pregnancy outcome in one in vitro fertilization cycle. Fang Y et al. (2016) To determine whether the levels of CBP/p300 interacting transactivator with ED-rich tail 2 (Cited2) protein in cumulus cells (CCs) derived from patients undergoing IVF related to infertility factors, embryo quality, and clinical outcomes in one IVF cycle. Retrospective analysis of human CCs. Public hospital and university. A total of 103 (conventional) IVF patients and 32 intracytoplasmic sperm injection patients. All CCs from each patient's oocytes were considered as one sample. The patients were divided into two groups according to whether the Cited2/β-actin levels in their CCs were above or below the mean level detected for all patients. Embryo quality and clinical outcomes of IVF patients. The oocytes derived from the group of patients whose CCs showed lower Cited2 levels displayed higher fertilization, transferable embryo, and implantation rates. Moreover, the patients in this group were more likely to have a successful pregnancy outcome. Among different infertility factors, a total of 78.6% of patients with polycystic ovary syndrome had a higher Cited2 level in CCs. Additionally, patients with a lower basal FSH level belonged to the higher Cited2 levels group. The expression of two genes (phosphoenolpyruvate carboxykinase 1 [PCK1] and progesterone receptor [PR]) and the glucose content in CCs were also markedly increased in CCs derived from patients with higher Cited2 levels. The present findings imply that Cited2 level in CCs is associated with polycystic ovary syndrome, embryo quality, and pregnancy outcome of IVF patients.//////////////////
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Mutations |
2 mutations
Species: mouse
Mutation name: None
type: null mutation
fertility: infertile - ovarian defect
Comment: Gonadal defects in Cited2 -mutant mice indicate a role for SF1 in both testis and ovary differentiation. Combes AN et al. Sex determination is regulated by a molecular antagonism between testis- and ovary-determining pathways in the supporting cell lineage of the gonadal primordia. Genes important for maintaining this lineage play critical roles in early gonadal development, but their influence on testis and ovary differentiation is unclear due to the severity of loss-of-function phenotypes. The transcription factor SF1 (Nr5a1/Ad4BP) is one such factor, required for establishing the supporting cell lineage, and for propagating the male pathway. In the gonad, Sf1 expression is enhanced by the transcriptional co-factor Cited2. We have used the reduced levels of Sf1 expression in Cited2 (-/-) mice as a hypomorphic model to gain insight into the sex-specific roles of SF1 function in gonadal development. In XY mutant mice, we found that testis development was delayed in Cited2 (-/-) gonads, and that testis structure was permanently disrupted. In XX Cited2 (-/-) gonads, ectopic cell migration was observed which correlated with a transient upregulation of Fgf9, and a delay in Wnt4 then Foxl2 expression. These data suggest a novel role for SF1 in promoting ovarian development in addition to its roles in testis differentiation.
Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: CITED2 mutations potentially cause idiopathic premature ovarian failure. Fonseca DJ et al. (2013) Anomalies in gonadal development in a mouse knockout model of Cited2 have been recently described. In Cited2(-/-) female gonads, an ectopic cell migration was observed and the female program of sex determination was transiently delayed. We hypothesize that, in humans, this temporary inhibition of genes should be sufficient to provoke a developmental impairment of the female gonads, conducive to premature ovarian failure (POF). To establish whether CITED2 mutations are a common cause of the disease, we performed a mutational analysis of this gene in a panel of patients with POF and in a group of control women with normal fertility. We amplified and directly sequenced the complete open reading frame of CITED2 in 139 patients with POF and 290 controls. This study revealed 5 synonymous and 3 nonsynonymous variants. Among these, 7 are novel. The nonsynonymous variant c.604C>A (p.Pro202Thr) was found uniquely in 1 woman from the POF group. In silico analysis of this mutation indicated a potential deleterious effect. We conclude that mutations in CITED2 may be involved in POF pathogenesis.//////////////////
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