Objective To investigate the effect of membrane-spanning 4-domains subfamily member 6D(MS4A6D)gene knockout on the fertility of female mice.Methods On the basis of the successful construction of Ms4a6d gene knockout model mice,the homozygous Ms4a6d gene knockout(Ms4a6d-/-)mice at an age of different weeks were subjected.Mouse genotype was identified with RT-qPCR and agarose gel electrophoresis.HE staining,immunofluorescence assay and ELISA were used to detect serum level of anti-müllerian hormone(AMH),composition of macrophages and follicles at all levels in the ovaries of Ms4a6d-/mice,respectively.The fertility changes in pregnant rate and average litter size of female Ms4a6d-/-mice were observed by fertility experiments.Results Compared with the wild-type(Ms4a6d+/+)female mice at the same age,there were less macrophages in the ovarian tissues of the 2-and 4-week-old Ms4a6d-/-female mice(P＜0.01),but no significant difference was observed between the 2 types of mice at 8 weeks of age.For the adult Ms4a6d-/-female mice at an age of 8 weeks,the ovarian coefficient was obviously lower(P＜0.01),and the numbers of primordial,primary,secondary and antral follicles in the ovarian tissues was statistically lower(P＜0.05)when compared with the adult wild-type female mice at the same age.The serum AMH level was notably lower in the Ms4a6d-/-female mice of all ages than the wild-type ones at corresponding ages(P＜0.05).The average pregnancy rate was 56％and the litter size was 4.1±1.1 in adult Ms4a6d-/-female mice,which were significantly lower than those of wild-type mice of the same age(89％and 6.3±1.2).Conclusion Ms4a6d gene knockout decreases the number of macrophages in the ovarian tissues of adolescent females,interferes with the development of follicles in the ovarian tissues of adolescent females,and leads to a decrease in ovarian reserve in adult females and a decrease in fertility in adult females.