| First Author | Sun Z | Year | 2018 |
| Journal | Cell Death Differ | Volume | 25 |
| Issue | 9 | Pages | 1686-1701 |
| PubMed ID | 29467381 | Mgi Jnum | J:268917 |
| Mgi Id | MGI:6269783 | Doi | 10.1038/s41418-018-0067-x |
| Citation | Sun Z, et al. (2018) TMCO1 is essential for ovarian follicle development by regulating ER Ca(2+) store of granulosa cells. Cell Death Differ 25(9):1686-1701 |
| abstractText | TMCO1 (transmembrane and coiled-coil domains 1) is an endoplasmic reticulum (ER) transmembrane protein that actively prevents Ca(2+) stores from overfilling. To characterize its physiological function(s), we generated Tmco1(-/-) knockout (KO) mice. In addition to the main clinical features of human cerebrofaciothoracic (CFT) dysplasia spectrum, Tmco1(-/-) females manifest gradual loss of ovarian follicles, impaired ovarian follicle development, and subfertility with a phenotype analogous to the premature ovarian failure (POF) in women. In line with the role of TMCO1 as a Ca(2+) load-activated Ca(2+) channel, we have detected a supernormal Ca(2+) signaling in Tmco1(-/-) granulosa cells (GCs). Interestingly, although spontaneous Ca(2+) oscillation pattern was altered, ER Ca(2+) stores of germinal vesicle (GV) stage oocytes and metaphase II (MII) arrested eggs were normal upon Tmco1 ablation. Combined with RNA-sequencing analysis, we also detected increased ER stress-mediated apoptosis and enhanced reactive oxygen species (ROS) level in Tmco1(-/-) GCs, indicating the dysfunctions of GCs upon TMCO1 deficiency. Taken together, these results reveal that TMCO1 is essential for ovarian follicle development and female fertility by maintaining ER Ca(2+) homeostasis of GCs, disruption of which causes ER stress-mediated apoptosis and increased cellular ROS level in GCs and thus leads to impaired ovarian follicle development. |
