Rabbit Anti-Human CCNO Polyclonal Antibody

The aryl hydrocarbon receptor (AhR), a transcription factor known for mediating xenobiotic toxicity, is expressed in B cells, which are known targets for environmental pollutants. However, it is unclear what the physiological functions of AhR in B cells are. We show here that expression of Ahr in B cells is up-regulated upon B-cell receptor (BCR) engagement and IL-4 treatment. Addition of a natural ligand of AhR, FICZ, induces AhR translocation to the nucleus and transcription of the AhR target gene Cyp1a1, showing that the AhR pathway is functional in B cells. AhR-deficient (Ahr(-/-)) B cells proliferate less than AhR-sufficient (Ahr(+/+)) cells following invitro BCR stimulation and invivo adoptive transfer models confirmed that Ahr(-/-) B cells are outcompeted by Ahr(+/+) cells. Transcriptome comparison of AhR-deficient and AhR-sufficient B cells identified cyclin O (Ccno), a direct target of AhR, as a top candidate affected by AhR deficiency.

Infertility affects 10% of reproductive-age women and is extremely heterogeneous in etiology. The genetic contribution to female infertility is incompletely understood, and involves chromosomal and single-gene defects. Our aim in this study is to decipher single-gene causes in infertile women in whom endocrinological, anatomical, and chromosomal causes have been excluded. Our cohort comprises women with recurrent pregnancy loss and no offspring from spontaneous pregnancies (RPL, n = 61) and those who never achieved clinical pregnancy and were referred for in vitro fertilization [primary infertility (PI), n = 14]. Whole-exome sequencing revealed candidate variants in 14, which represents 43% of those with PI and 13% of those with RPL. These include variants in previously established female infertility-related genes (TLE6, NLRP7, FSHR, and ZP1) as well as genes with only tentative links in the literature (NLRP5). Candidate variants in genes linked to primary ciliary dyskinesia (DNAH11 and CCNO) were identified in individuals with and without systemic features of the disease. We also identified variants in genes not previously linked to female infertility. These include one homozygous variant each in CCDC68, CBX3, CENPH, PABPC1L, PIF1, PLK1, and REXO4, which we propose as candidate genes for infertility based on their established biology or compatible animal models. Our study expands the contribution of single genes to the etiology of PI and RPL, improves the precision of disease classification at the molecular level, and offers the potential for future treatment and development of human genetics-inspired fertility regulators.