1.Human amniotic mesenchymal stem cells improve ovarian function and endometrial receptivity in mice with autoimmune premature ovarian insufficiency
Linyan LI ; Rongxia LIU ; Linshen PENG ; Zhenhai FAN ; Qing HE ; Hui CHEN ; Limei YU
Chinese Journal of Reproduction and Contraception 2021;41(12):1062-1070
Objective:To investigate the effect of human amniotic mesenchymal stem cells (hAMSCs) on ovarian function and endometrial receptivity in mice with autoimmune premature ovarian insufficiency (POI).Methods:POI mouse was induced by treatment with zona pellucida 3 polypeptide fragment-Freund immune adjuvant. The animals were divided into normal group ( n=10), model group ( n=15) and hAMSCs group ( n=15). hAMSCs (1×10 6 cells/mouse) were transplanted by tail vein single injection. The oestrus cycles were evaluated by vaginal smears. The levels of follicle-stimulating hormone (FSH), estrogen and anti-Müllerian hormone (AMH) in serum were detected by enzyme-linked immunosorbent assay methods. Morphological changes of ovarian and uterus tissues were observed after HE staining. The expressions of homeobox A10 (HOXA10), tumor necrosis factor-α (TNF-α) and FSH receptor (FSHR) proteins in uterine were measured by immunohistochemistry. The endometrial receptivity was comprehensively assessed. Results:After hAMSCs transplanting 6 weeks, the rate of abnormal oestrus cycles in hAMSCs group [40.0% (6/15)] was lower than that in model group [86.7% (13/15), P=0.021]. Compared with the levels of serum FSH [(10.239±1.091) μg/L], estradiol [(103.325±4.952) ng/L] and AMH [(1.133±0.494) μg/L] in model group, the level of FSH in hAMSCs group [(7.664±0.735) μg/L] was significantly decreased ( P<0.001), the levels of estradiol [(126.883±23.370) ng/L] and AMH [(2.204±0.453) μg/L] were significantly increased in hAMSCs group ( P=0.015, P<0.001). Different from model group, the ovarian and uterine index were increased. A large number of healthy follicles at all stages were highly increased, but it was rare to find interstitial fibrosis and atresia follicles. The uterine wall and endometrium were thickened, and the number and volume of the glands were increased. The absorbance ( A) of HOXA10 in hAMSCs group (5.90±1.94) was higher than that in model group (2.79±1.27, P=0.029). The TNF-α A value of hAMSCs (3.83±1.23) group was significantly lower than that of model group (6.26±0.96, P=0.002). Although there was no significant difference on FSHR A value between hAMSCs group (3.61±1.66) and model group (2.74±0.22, P>0.05), the FSHR A value of model group was lower than that of normal group (4.13±0.54, P=0.006). Conclusion:hAMSCs transplantation could restore ovarian function of autoimmune POI mice meanwhile significantly improve uterine receptivity and fertility.
2.Human amniotic mesenchymal stem cells improve ovarian function and endometrial receptivity in mice with autoimmune premature ovarian insufficiency
Linyan LI ; Rongxia LIU ; Linshen PENG ; Zhenhai FAN ; Qing HE ; Hui CHEN ; Limei YU
Chinese Journal of Reproduction and Contraception 2021;41(12):1062-1070
Objective:To investigate the effect of human amniotic mesenchymal stem cells (hAMSCs) on ovarian function and endometrial receptivity in mice with autoimmune premature ovarian insufficiency (POI).Methods:POI mouse was induced by treatment with zona pellucida 3 polypeptide fragment-Freund immune adjuvant. The animals were divided into normal group ( n=10), model group ( n=15) and hAMSCs group ( n=15). hAMSCs (1×10 6 cells/mouse) were transplanted by tail vein single injection. The oestrus cycles were evaluated by vaginal smears. The levels of follicle-stimulating hormone (FSH), estrogen and anti-Müllerian hormone (AMH) in serum were detected by enzyme-linked immunosorbent assay methods. Morphological changes of ovarian and uterus tissues were observed after HE staining. The expressions of homeobox A10 (HOXA10), tumor necrosis factor-α (TNF-α) and FSH receptor (FSHR) proteins in uterine were measured by immunohistochemistry. The endometrial receptivity was comprehensively assessed. Results:After hAMSCs transplanting 6 weeks, the rate of abnormal oestrus cycles in hAMSCs group [40.0% (6/15)] was lower than that in model group [86.7% (13/15), P=0.021]. Compared with the levels of serum FSH [(10.239±1.091) μg/L], estradiol [(103.325±4.952) ng/L] and AMH [(1.133±0.494) μg/L] in model group, the level of FSH in hAMSCs group [(7.664±0.735) μg/L] was significantly decreased ( P<0.001), the levels of estradiol [(126.883±23.370) ng/L] and AMH [(2.204±0.453) μg/L] were significantly increased in hAMSCs group ( P=0.015, P<0.001). Different from model group, the ovarian and uterine index were increased. A large number of healthy follicles at all stages were highly increased, but it was rare to find interstitial fibrosis and atresia follicles. The uterine wall and endometrium were thickened, and the number and volume of the glands were increased. The absorbance ( A) of HOXA10 in hAMSCs group (5.90±1.94) was higher than that in model group (2.79±1.27, P=0.029). The TNF-α A value of hAMSCs (3.83±1.23) group was significantly lower than that of model group (6.26±0.96, P=0.002). Although there was no significant difference on FSHR A value between hAMSCs group (3.61±1.66) and model group (2.74±0.22, P>0.05), the FSHR A value of model group was lower than that of normal group (4.13±0.54, P=0.006). Conclusion:hAMSCs transplantation could restore ovarian function of autoimmune POI mice meanwhile significantly improve uterine receptivity and fertility.

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