Background Exogenous gonadotropin-controlled ovarian stimulation is the critical step in animal reproductive management,such as pig,sheep,bovine and other species.It helps synchronize ovulation or stimulate multiple o...Background Exogenous gonadotropin-controlled ovarian stimulation is the critical step in animal reproductive management,such as pig,sheep,bovine and other species.It helps synchronize ovulation or stimulate multiple ovu-lations.However,a number of evidence indicated an unexpected decrease in pregnancy outcomes following ovarian stimulation.This study aimed to explore the underlying mechanism of the pregnancy defect and develop a practical rescue strategy.Results Compared with those in the control group,gilts that underwent ovarian stimulation showed a decrease in pregnancy rate,farrowing rate,and total number of piglets born.Stimulated gilts also showed an increase in estra-diol(E_(2))levels.The supraphysiologicalE_(2) level was correlated with the decrease in the number of piglets born.Furthermore,we found that high levels ofE_(2) impair uterine receptivity,as shown by the overproliferation of endo-metrial epithelial cells.In vitro mechanistic studies demonstrated that high levels ofE_(2) hyperactivate FGF-FGFR-ERK signaling cascade in the uterine endometrium,and in turn induces overproliferation of endometrial epithelial cells.Of note,N-acetyl-L-cysteine(NAC)supplementation effectively inhibits ERK hyperphosphorylation and ameliorates endometrial epithelial overproliferation.Importantly,in vivo experiments indicated that dietary NAC supplementa-tion,compared with ovarian stimulation group,improves the uterine receptivity in gilts,and significantly increases the pregnancy rate and total number of piglets born.Conclusions Ovarian stimulation-induced supraphysiological levels ofE_(2) impairs uterine receptivity by hyperactivat-ing FGF-FGFR-ERK signaling cascade,thereby reducing pregnancy rate and litter size.Supplementing NAC to a con-ventional diet for gilts ameliorates hyperactivated ERK signaling and improves uterine receptivity,thus rescuing adverse pregnancy outcomes following ovarian stimulation.展开更多
Objective To explore the potencial relationship between hysteroscopic findings,and the concentrationa of leukaemia inhibitory factor (LIF) in uterine flushing as well as the expression of LIF in the endometriumMethods...Objective To explore the potencial relationship between hysteroscopic findings,and the concentrationa of leukaemia inhibitory factor (LIF) in uterine flushing as well as the expression of LIF in the endometriumMethods Hysteroscopy was carried out among 64 infertile female patients and uterine flushing was collected for LIF assay in the mid-secretory phase. All subjects were classified according to the appearance of the glandular openings and the blood vessels on the endometrium surface into Group I and Group II. An ELISA kit specific for human LIF was used for LIF assay.Results The median LIF concentrations measured in Group I and Group II -were 14. 375±15. 155pg/mL and 61. 696+ 44. 127 pg/mL. The difference of LIF concentration was statistically significant (P< 0. 05) between Group I and Group II. But no significant difference between Group II and the proliferative endometrium (11. 02± 11. 07 pg/mL) was found. The average expression of LIF mRNA in Group I was 0. 93± 0. 20, and 1. 55± 0. 08 in Group II. The expression of LIF mRNA in the endometrium from Group I was much lower than that from the decidua of early pregnancy (1. 65±0. 18) , while no significant difference was observed between Group II and the decidua of. early pregnancy.Conclusion There is a strong relationship between endoscopic findings and the concentration of LIF. Our data suggested that the hysteroscopic appearance of the mid-secretory endometrium and measurement of LIF in uterine flushing are better evaluation factors for the uterine receptivity.展开更多
基金National Natural Science Foundation of China(31930103)National Center of Technology Innovation for Pigs(NCTIP-XD/B03)+2 种基金Ningbo Major Science and Technology Project(2021Z112)National Key R&D Program(2022YFD1300303)Beijing Innovation Consortium of Livestock Research System BAIC05-2024.
文摘Background Exogenous gonadotropin-controlled ovarian stimulation is the critical step in animal reproductive management,such as pig,sheep,bovine and other species.It helps synchronize ovulation or stimulate multiple ovu-lations.However,a number of evidence indicated an unexpected decrease in pregnancy outcomes following ovarian stimulation.This study aimed to explore the underlying mechanism of the pregnancy defect and develop a practical rescue strategy.Results Compared with those in the control group,gilts that underwent ovarian stimulation showed a decrease in pregnancy rate,farrowing rate,and total number of piglets born.Stimulated gilts also showed an increase in estra-diol(E_(2))levels.The supraphysiologicalE_(2) level was correlated with the decrease in the number of piglets born.Furthermore,we found that high levels ofE_(2) impair uterine receptivity,as shown by the overproliferation of endo-metrial epithelial cells.In vitro mechanistic studies demonstrated that high levels ofE_(2) hyperactivate FGF-FGFR-ERK signaling cascade in the uterine endometrium,and in turn induces overproliferation of endometrial epithelial cells.Of note,N-acetyl-L-cysteine(NAC)supplementation effectively inhibits ERK hyperphosphorylation and ameliorates endometrial epithelial overproliferation.Importantly,in vivo experiments indicated that dietary NAC supplementa-tion,compared with ovarian stimulation group,improves the uterine receptivity in gilts,and significantly increases the pregnancy rate and total number of piglets born.Conclusions Ovarian stimulation-induced supraphysiological levels ofE_(2) impairs uterine receptivity by hyperactivat-ing FGF-FGFR-ERK signaling cascade,thereby reducing pregnancy rate and litter size.Supplementing NAC to a con-ventional diet for gilts ameliorates hyperactivated ERK signaling and improves uterine receptivity,thus rescuing adverse pregnancy outcomes following ovarian stimulation.
文摘Objective To explore the potencial relationship between hysteroscopic findings,and the concentrationa of leukaemia inhibitory factor (LIF) in uterine flushing as well as the expression of LIF in the endometriumMethods Hysteroscopy was carried out among 64 infertile female patients and uterine flushing was collected for LIF assay in the mid-secretory phase. All subjects were classified according to the appearance of the glandular openings and the blood vessels on the endometrium surface into Group I and Group II. An ELISA kit specific for human LIF was used for LIF assay.Results The median LIF concentrations measured in Group I and Group II -were 14. 375±15. 155pg/mL and 61. 696+ 44. 127 pg/mL. The difference of LIF concentration was statistically significant (P< 0. 05) between Group I and Group II. But no significant difference between Group II and the proliferative endometrium (11. 02± 11. 07 pg/mL) was found. The average expression of LIF mRNA in Group I was 0. 93± 0. 20, and 1. 55± 0. 08 in Group II. The expression of LIF mRNA in the endometrium from Group I was much lower than that from the decidua of early pregnancy (1. 65±0. 18) , while no significant difference was observed between Group II and the decidua of. early pregnancy.Conclusion There is a strong relationship between endoscopic findings and the concentration of LIF. Our data suggested that the hysteroscopic appearance of the mid-secretory endometrium and measurement of LIF in uterine flushing are better evaluation factors for the uterine receptivity.
