PMID- 35128892 OWN - NLM STAT- MEDLINE DCOM- 20220208 LR - 20220208 IS - 1005-6661 (Print) IS - 1005-6661 (Linking) VI - 33 IP - 6 DP - 2021 Apr 16 TI - [Expression of hypoxia-inducible factor-1 in mice infected with Toxoplasma gondii during pregnancy]. PG - 615-622 LID - 10.16250/j.32.1374.2021122 [doi] AB - OBJECTIVE: To investigate the expression and possible role of hypoxia-inducible factor-1 (HIF-1) at the maternal-fetal interface following Toxoplasma gondii infection during early pregnancy. METHODS: Twenty pregnant C57BL/6 mice, each weighing 16 to 20 g, were randomly divided into 4 groups, including the 12-d control group, 12-d infection group, 18-d control group and 18-d infection group. Mice in the 12-d and 18-d infection groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain on day 6 of pregnancy, while mice in the 12-d control and 18-d control groups were injected with the same volume of phosphate buffered saline (PBS). Mice in the control and infection groups were sacrificed on days 12 and 18 of pregnancy, and the placental and uterine specimens of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of HIF-1alpha, HIF-1beta and vascular endothelial growth factor (VEGF) was quantified using quantitative fluorescent real-time PCR (qPCR) assay in the placental and uterine specimens, and the correlation between HIF-1alpha and VEGF mRNA expression was examined. In addition, and the HIF-1alpha expression was detected using immunohistochemical staining in the placental and uterine specimens of pregnant mice. RESULTS: Compared with the 12-d and 18-d control groups, adverse pregnant outcomes were observed in mice in 12-d and 18-d infection groups, such as teratism and placental dysplasia. HE staining showed swelling and blood stasis of cells, sinusoid reduction and inflammatory cell infiltration in the labyrinth area of the placenta specimens of mice in 12-d and 18-d infection groups relative to 12-d and 18-d control groups, and columnar epithelial cell injury and inflammatory cell infiltration were seen in the mouse uterine specimens in both infection groups. qPCR assay detected significantly higher HIF-1alpha (F = 132.6, P < 0.05) and HIF-1beta mRNA expression (F = 286.9, P < 0.05) in the placental specimens and lower HIF-1alpha (F = 111.5, P < 0.05) and HIF-1beta mRNA expression (F = 55.2, P < 0.05) in the uterine specimens in the 12-d infection group than in the 12-day control group, and significantly lower HIF-1alpha and HIF-1beta mRNA expression was detected in the placental and uterine specimens in the 18-d infection group than in the 18-day control group (F = 215.8, 418.9, 156.8 and 200.1; all P values < 0.05). Significantly lower VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the placental specimens and higher VEGF-A (F = 426.2, P < 0.05), VEGF-B (F = 104.6, P < 0.05) and VEGF-C mRNA expression (F = 566.9, P < 0.05) in the uterine specimens were detected in the 12-d infection group than in the 12-d control group, and higher VEGF-A, VEGF-B and VEGF-C mRNA expression was found in the placental and uterine specimens in the 18-d infection group than in the 18-d control group (F = 521.9, 100.6, 275.9, 224.6, 108.2 and 333.4; all P values < 0.05). Immunohistochemical staining showed strongly and mildly positive HIF-1alpha expression in the mouse placental labyrinth area in the 12-d and 18-d infection groups relative to 12-d and 18-d control groups, while no HIF-1alpha expression was detected in mouse uterine specimens. CONCLUSIONS: HIF-1alpha expression appears a tendency towards a rise in the second trimester and a reduction in the third trimester in mice following T. gondii infection during early pregnancy, which is contrary to the changing tendency of VEGF-A, VEGF-B, and VEGF-C expression. It is hypothesized that HIF-1alpha inhibits placental angiogenesis in mice during pregnancy through suppressing VEGF expression, resulting in adverse pregnant outcomes. FAU - Zeng, Y L AU - Zeng YL AD - Department of Parasitology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi 530021, China. FAU - Xue, S AU - Xue S AD - Department of Parasitology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi 530021, China. FAU - Bi, X L AU - Bi XL AD - Department of Parasitology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi 530021, China. FAU - Yan, L X AU - Yan LX AD - Department of Parasitology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi 530021, China. FAU - Yang, J AU - Yang J AD - Department of Parasitology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi 530021, China. FAU - Zhang, D Y AU - Zhang DY AD - Department of Parasitology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi 530021, China. FAU - Gou, Y S AU - Gou YS AD - Department of Parasitology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi 530021, China. FAU - Fu, X Y AU - Fu XY AD - Department of Parasitology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi 530021, China. FAU - Liu, D Y AU - Liu DY AD - Department of Parasitology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi 530021, China. LA - chi GR - 81760370/National Natural Science Foundation of China/ GR - 2017GXNSFBA198154/Natural Science Foundation of Guangxi Zhuang Autonomous Region/ PT - Journal Article PL - China TA - Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi JT - Zhongguo xue xi chong bing fang zhi za zhi = Chinese journal of schistosomiasis control JID - 101144973 RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Animals MH - Female MH - Hypoxia MH - Mice MH - Mice, Inbred C57BL MH - Placenta MH - Pregnancy MH - *Toxoplasma MH - *Vascular Endothelial Growth Factor A OTO - NOTNLM OT - Hypoxia inducible factor-1 OT - Mouse OT - Pregnancy OT - Toxoplasma gondii OT - Vascular endothelial growth factor EDAT- 2022/02/08 06:00 MHDA- 2022/02/09 06:00 CRDT- 2022/02/07 05:42 PHST- 2022/02/07 05:42 [entrez] PHST- 2022/02/08 06:00 [pubmed] PHST- 2022/02/09 06:00 [medline] AID - 10.16250/j.32.1374.2021122 [doi] PST - ppublish SO - Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi. 2021 Apr 16;33(6):615-622. doi: 10.16250/j.32.1374.2021122.