Uterine Deletion of Bmal1 Impairs Placental Vascularization and Induces Intrauterine Fetal Death in Mice
| Autor: | Masanori Ono, Natsumi Toyoda, Kyosuke Kagami, Takashi Hosono, Takeo Matsumoto, Shin-ichi Horike, Rena Yamazaki, Mitsuhiro Nakamura, Yasunari Mizumoto, Tomoko Fujiwara, Hitoshi Ando, Hiroshi Fujiwara, Takiko Daikoku |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | International Journal of Molecular Sciences, Vol 23, Iss 14, p 7637 (2022) |
| Druh dokumentu: | article |
| ISSN: | 1422-0067 1661-6596 |
| DOI: | 10.3390/ijms23147637 |
| Popis: | Recently, it was demonstrated that the expression of BMAL1 was decreased in the endometrium of women suffering from recurrent spontaneous abortion. To investigate the pathological roles of uterine clock genes during pregnancy, we produced conditional deletion of uterine Bmal1 (cKO) mice and found that cKO mice could receive embryo implantation but not sustain pregnancy. Gene ontology analysis of microarray suggested that uterine NK (uNK) cell function was suppressed in cKO mice. Histological examination revealed the poor formation of maternal vascular spaces in the placenta. In contrast to WT mice, uNK cells in the spongiotrophoblast layer, where maternal uNK cells are directly in contact with fetal trophoblast, hardly expressed an immunosuppressive NK marker, CD161, in cKO mice. By progesterone supplementation, pregnancy could be sustained until the end of pregnancy in some cKO mice. Although this treatment did not improve the structural abnormalities of the placenta, it recruited CD161-positive NK cells into the spongiotrophoblast layer in cKO mice. These findings indicate that the uterine clock system may be critical for pregnancy maintenance after embryo implantation. |
| Databáze: | Directory of Open Access Journals |
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