Effects of superovulation induced by gonadotropin and human chorionic gonadotropin on the uterus of mice

赵航1杨娜娜1吴兴龙1李相运1*刘宜勇2*

doi:10.16098/j.issn.0529-1356.2026.04.011

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Acta Anatomica Sinica ›› 2026, Vol. 57 ›› Issue (4) : 475-483. DOI: 10.16098/j.issn.0529-1356.2026.04.011

Histology and Embryology and Development Biology

Effects of superovulation induced by gonadotropin and human chorionic gonadotropin on the uterus of mice

ZHAO Hang¹, YANG Na-na¹, WU Xing-long¹, LI Xiang-yun^1*, LIU Yi-yong^2*

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Abstract

Objective To investigate the adverse effects of superovulatory hormone treatment on the uterus of mice. Methods Twenty-seven female mice were divided into the superovulation recipient group and the normal recipient group (control group, injected with normal saline). For the superovulation recipient group, each mouse was intraperitoneally injected with 7.5 IU pregnant mare serum gonadotropin (PMSG), followed by an injection of 7.5 IU human chorionic gonadotropin (HCG) after 48 hours. All recipients were pseudopregnant mice obtained by cohabitation with vasectomized male mice. In experiment 1, 3.5-day-old blastocysts were transferred into the uteri of recipients in both groups via surgical method, and the implantation rate was subsequently calculated and recorded. In experiment 2, after the blastocysts were transferred into the recipients’ uteri, the embryos were flushed out on 1, 3 and 6 hours post-transfer, respectively, and the morphological changes of the embryos were observed. Omics analysis was performed on the uterine tissue samples collected from normal recipients and superovulation recipients. Results Blastocysts of 3.5 days were separately transferred into the normal and superovulation recipient mice. The embryo implantation rate of the superovulation recipient group was 42.74% on 7.5 days post-transfer, which was significantly lower than that of 74.34% in the normal recipient group (P<0.01). After the embryos were transferred into the uteri of the two recipient groups respectively, the embryos in the uteri of superovulation recipients exhibited varying degrees of damage at different time points, whereas the embryos in the uteri of normal recipients only underwent normal growth and development. For transcriptomic analysis, endometrial tissue samples were collected from recipients on 2.5 days post-treatment, and a total of 1479 differentially expressed genes (DEGs) were identified, including 951 up-regulated genes and 528 down-regulated genes. Among them, 9 significantly up-regulated genes (such as ctla-2α, LCN2 and GPX3) were mainly involved in biological processes including regulation of inflammatory response, oxidative stress and immune effector process. Metabolomic analysis was conducted on uterine tissue samples collected from recipients on 2.5 days post-treatment, and a total of 161 significantly differential metabolites were screened out. Specifically, 55 metabolites were up-regulated and 37 were down-regulated in the positive ion mode, while 53 were up-regulated and 16 were down-regulated in the negative ion mode. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that these differential metabolites were mainly enriched in pathways related to metabolic processes. Conclusion After superovulatory hormone treatment, abnormalities in the uterine immune microenvironment and metabolic disorders occur in mice, which impairs the quality of transplanted embryos and thereby reduces the implantation rate.

Key words

Uterus

/ Superovulation / Embryo transfer / Gonadotropin / Human chorionic gonadotropin / Omics analysis / Mouse

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ZHAO Hang , YANG Na-na , WU Xing-long , LI Xiang-yun , LIU Yi-yong.

Effects of superovulation induced by gonadotropin and human chorionic gonadotropin on the uterus of mice

[J]. Acta Anatomica Sinica. 2026, 57(4): 475-483 https://doi.org/10.16098/j.issn.0529-1356.2026.04.011

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