title: Loss of Bmal1 decreases oocyte fertilization, early embryo development and implantation potential in female mice.
abstract: Biological clock genes expressed in reproductive tissues play important roles in maintaining the normal functions of reproductive system. However, disruption of female circadian rhythm on oocyte fertilization, preimplantation embryo development and blastocyst implantation potential is still unclear. In this study, ovulation, in vivo and in vitro oocyte fertilization, embryo development, implantation and intracellular reactive oxygen species (ROS) levels in ovary and oviduct were studied in female Bmal1+/+ and Bmal1-/- mice. The number of naturally ovulated oocyte in Bmal1-/- mice decreased (5.2 ± 0.8 vs 7.8 ± 0.8, P < 0.001), with an increasing abnormal oocyte ratio (20.4 ± 3.5 vs 11.7 ± 2.0%, P = 0.001) after superovulation. Significantly lower fertilization rate and obtained blastocyst number were observed in Bmal1-/- female mice either mated with wild-type in vivo or fertilized by sperm from wild-type male mice in vitro (all P < 0.05). Interestingly, in vitro fertilization rate of oocytes derived from Bmal1-/- increased significantly compared with in vivo study (P < 0.01). After transferring blastocysts derived from Bmal1+/+ and Bmal1-/- female mice to pseudopregnant mice, the implantation sites of the latter decreased 5 days later (8.0 ± 0.8 vs 5.3 ± 1.0, P = 0.005). The intracellular ROS levels in the ovary on proestrus day and in the oviduct on metestrus day increased significantly in Bmal1-/- mice compared with that of Bmal1+/+ mice. Deletion of the core biological clock gene Bmal1 significantly decreases oocyte fertilization rate, early embryo development and implantation potential in female mice, and these may be possibly caused by excess ROS levels generated in ovary and oviduct.
authors.affiliation: Reproductive Medicine Center,Guangzhou Women and Children's Medical Center,Guangzhou,Guangzhou Medical University,China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Reproductive Medicine Center,Henan Provincial People's Hospital,Zhengzhou,Henan,China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Reproductive Medicine Center,First Affiliated Hospital of Sun Yat-sen University,Guangzhou,China;Guangdong Provincial Key Laboratory of Reproductive Medicine,Guangdong,China.
authors.forename: Yizi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Reproductive Medicine Center,First Affiliated Hospital of Sun Yat-sen University,58 Zhongshan Road II,Guangzhou,China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Reproductive Medicine Center,First Affiliated Hospital of Sun Yat-sen University,58 Zhongshan Road II,Guangzhou,China.
authors.forename: Canquan
authors.initials: C
authors.lastname: Zhou
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001755:Blastocyst / Q000502:physiology*; D010064:Embryo Implantation / Q000235:genetics*; D005187:Fallopian Tubes / Q000378:metabolism; D005260:Female; D005306:Fertilization / Q000235:genetics / Q000502:physiology*; D005307:Fertilization in Vitro; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009865:Oocytes / Q000473:pathology / Q000502:physiology*; D010053:Ovary / Q000378:metabolism; D010060:Ovulation / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013480:Superovulation / Q000235:genetics
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D017382:Reactive Oxygen Species
keywords: Bmal1−/−
                  mice; Embryo development; Fertilization; Implantation; ROS