Transcriptome profiling reveals superovulation with the gonadotropin-releasing hormone agonist trigger impaired embryo implantation in mice
IntroductionSuperovulation is a critical step in assisted reproductive technology, but the use of human chorionic gonadotropin (hCG) as a trigger for superovulation can result in ovarian hyperstimulation. Thus, the use of Gonadotropin-releasing hormone agonist (GnRHa) trigger has been increasingly a...
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| Format: | Article |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2024.1354435/full |
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| author | Meng Li Jingmei Han Nana Yang Xiangyun Li Xinglong Wu |
| author_facet | Meng Li Jingmei Han Nana Yang Xiangyun Li Xinglong Wu |
| author_sort | Meng Li |
| collection | DOAJ |
| description | IntroductionSuperovulation is a critical step in assisted reproductive technology, but the use of human chorionic gonadotropin (hCG) as a trigger for superovulation can result in ovarian hyperstimulation. Thus, the use of Gonadotropin-releasing hormone agonist (GnRHa) trigger has been increasingly adopted, although it has been associated with a higher rate of pregnancy failure compared to natural cycles. This study aimed to investigate the effect of GnRHa trigger on embryo implantation in a mouse model.MethodsMice in the superovulation (PG) group were administered 7.5 IU of PMSG, followed by the injection of 3.5 μg of GnRHa (Leuprorelin) 48 h later, while mice in the control group (CTR) mated naturally. We compared the number of oocytes, blastocysts, and corpus luteum between the two groups and the implantation sites after the transfer of natural blastocysts. Ovaries, uterus, and serum 2 and 4 days after mating were collected for qRT-PCR, transcriptome sequencing, and hormone assays.ResultsThe PG group had more oocytes, blastocysts, and corpus luteum after superovulation than the CTR group. However, the mRNA expression of leukemia inhibitory factor (Lif) and the number of implantation sites were reduced in the PG group. The ELISA assay revealed that superovulation increased ovarian estrogen secretion. The transcriptome analysis showed that superphysiological estrogen led to a response of the uterus to a high estrogen signal, resulting in abnormal endometrium and extracellular matrix remodeling and up-regulation of ion transport and inflammation-related genes.ConclusionOur findings suggest that a combination of PMSG and GnRHa trigger impaired embryo implantation in mice, as the excessive uterine response to superphysiological estrogen levels can lead to the change of gene expression related to endometrial remodeling, abnormal expression of uterine ion transport genes and excessive immune-related genes. |
| first_indexed | 2024-03-07T21:43:50Z |
| format | Article |
| id | doaj.art-c697c1544fa54650b12c99849f90929c |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-07T21:43:50Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-c697c1544fa54650b12c99849f90929c2024-02-26T04:37:49ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-02-011510.3389/fendo.2024.13544351354435Transcriptome profiling reveals superovulation with the gonadotropin-releasing hormone agonist trigger impaired embryo implantation in miceMeng Li0Jingmei Han1Nana Yang2Xiangyun Li3Xinglong Wu4College of Animal Science and Technology, Hebei Technology Innovation Center of Cattle and Sheep Embryo, Hebei Agricultural University, Baoding, ChinaCollege of Veterinary Medicine, Hebei Agricultural University, Baoding, ChinaCollege of Animal Science and Technology, Hebei Technology Innovation Center of Cattle and Sheep Embryo, Hebei Agricultural University, Baoding, ChinaCollege of Animal Science and Technology, Hebei Technology Innovation Center of Cattle and Sheep Embryo, Hebei Agricultural University, Baoding, ChinaCollege of Animal Science and Technology, Hebei Technology Innovation Center of Cattle and Sheep Embryo, Hebei Agricultural University, Baoding, ChinaIntroductionSuperovulation is a critical step in assisted reproductive technology, but the use of human chorionic gonadotropin (hCG) as a trigger for superovulation can result in ovarian hyperstimulation. Thus, the use of Gonadotropin-releasing hormone agonist (GnRHa) trigger has been increasingly adopted, although it has been associated with a higher rate of pregnancy failure compared to natural cycles. This study aimed to investigate the effect of GnRHa trigger on embryo implantation in a mouse model.MethodsMice in the superovulation (PG) group were administered 7.5 IU of PMSG, followed by the injection of 3.5 μg of GnRHa (Leuprorelin) 48 h later, while mice in the control group (CTR) mated naturally. We compared the number of oocytes, blastocysts, and corpus luteum between the two groups and the implantation sites after the transfer of natural blastocysts. Ovaries, uterus, and serum 2 and 4 days after mating were collected for qRT-PCR, transcriptome sequencing, and hormone assays.ResultsThe PG group had more oocytes, blastocysts, and corpus luteum after superovulation than the CTR group. However, the mRNA expression of leukemia inhibitory factor (Lif) and the number of implantation sites were reduced in the PG group. The ELISA assay revealed that superovulation increased ovarian estrogen secretion. The transcriptome analysis showed that superphysiological estrogen led to a response of the uterus to a high estrogen signal, resulting in abnormal endometrium and extracellular matrix remodeling and up-regulation of ion transport and inflammation-related genes.ConclusionOur findings suggest that a combination of PMSG and GnRHa trigger impaired embryo implantation in mice, as the excessive uterine response to superphysiological estrogen levels can lead to the change of gene expression related to endometrial remodeling, abnormal expression of uterine ion transport genes and excessive immune-related genes.https://www.frontiersin.org/articles/10.3389/fendo.2024.1354435/fullsuperovulationgonadotropin-releasing hormone agonistuterine receptivityovarytranscriptome |
| spellingShingle | Meng Li Jingmei Han Nana Yang Xiangyun Li Xinglong Wu Transcriptome profiling reveals superovulation with the gonadotropin-releasing hormone agonist trigger impaired embryo implantation in mice Frontiers in Endocrinology superovulation gonadotropin-releasing hormone agonist uterine receptivity ovary transcriptome |
| title | Transcriptome profiling reveals superovulation with the gonadotropin-releasing hormone agonist trigger impaired embryo implantation in mice |
| title_full | Transcriptome profiling reveals superovulation with the gonadotropin-releasing hormone agonist trigger impaired embryo implantation in mice |
| title_fullStr | Transcriptome profiling reveals superovulation with the gonadotropin-releasing hormone agonist trigger impaired embryo implantation in mice |
| title_full_unstemmed | Transcriptome profiling reveals superovulation with the gonadotropin-releasing hormone agonist trigger impaired embryo implantation in mice |
| title_short | Transcriptome profiling reveals superovulation with the gonadotropin-releasing hormone agonist trigger impaired embryo implantation in mice |
| title_sort | transcriptome profiling reveals superovulation with the gonadotropin releasing hormone agonist trigger impaired embryo implantation in mice |
| topic | superovulation gonadotropin-releasing hormone agonist uterine receptivity ovary transcriptome |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2024.1354435/full |
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