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Dietary supplementation with N-acetyl-L-cysteine ameliorates hyperactivated ERK signaling in the endometrium that is linked to poor pregnancy outcomes following ovarian stimulation in pigs

dc.contributor.authorLinghua Cheng
dc.contributor.authorZhicheng Shi
dc.contributor.authorYuan Yue
dc.contributor.authorYue Wang
dc.contributor.authorYusheng Qin
dc.contributor.authorWei Zhao
dc.contributor.authorYupei Hu
dc.contributor.authorQin Li
dc.contributor.authorMin Guo
dc.contributor.authorLei An
dc.contributor.authorShumin Wang
dc.contributor.authorJianhui Tian
dc.contributor.otherFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University
dc.contributor.otherFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University
dc.contributor.otherFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University
dc.contributor.otherFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University
dc.contributor.otherFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University
dc.contributor.otherFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University
dc.contributor.otherFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University
dc.contributor.otherFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University
dc.contributor.otherFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University
dc.contributor.otherFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University
dc.contributor.otherFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University
dc.contributor.otherFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University
dc.date.accessioned2024-11-10T12:36:31Z
dc.date.available2025-10-02T05:03:49Z
dc.date.issued01-11-2024
dc.identifier.issn-
dc.identifier.urihttps://doi.org/10.1186/s40104-024-01109-1
dc.description.abstractAbstract 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 ovulations. 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 estradiol (E2) levels. The supraphysiological E2 level was correlated with the decrease in the number of piglets born. Furthermore, we found that high levels of E2 impair uterine receptivity, as shown by the overproliferation of endometrial epithelial cells. In vitro mechanistic studies demonstrated that high levels of E2 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 supplementation, 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 of E2 impairs uterine receptivity by hyperactivating FGF-FGFR-ERK signaling cascade, thereby reducing pregnancy rate and litter size. Supplementing NAC to a conventional diet for gilts ameliorates hyperactivated ERK signaling and improves uterine receptivity, thus rescuing adverse pregnancy outcomes following ovarian stimulation. Graphical Abstract
dc.format-
dc.language.isoEN
dc.publisherBMC
dc.relation.uri['http://www.ijccep.com', 'http://www.ijccep.com/authors/instructions']
dc.rightsCC BY
dc.subject['childhood education', 'educational policy and politics', 'Education (General)', 'L7-991', 'Special aspects of education', 'LC8-6691']
dc.subject.lccAnimal culture
dc.titleDietary supplementation with N-acetyl-L-cysteine ameliorates hyperactivated ERK signaling in the endometrium that is linked to poor pregnancy outcomes following ovarian stimulation in pigs
dc.typeArticle
dc.description.keywordsEstradiol
dc.description.keywordsGonadotropin
dc.description.keywordsImplantation
dc.description.keywordsN-acetyl-L-cysteine
dc.description.keywordsOvarian stimulation
dc.description.keywordsUterine receptivity
dc.description.pages1-15
dc.description.doi10.1186/s40104-024-01109-1
dc.title.journalJournal of Animal Science and Biotechnology
dc.identifier.e-issn2049-1891
dc.identifier.oaioai:doaj.org/journal:deb58a9296d647c3b53830033e6cb915
dc.journal.infoVolume 15, Issue 1


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