PMID- 34808452 OWN - NLM STAT- MEDLINE DCOM- 20220218 LR - 20220218 IS - 2300-732X (Electronic) IS - 1642-431X (Linking) VI - 21 IP - 4 DP - 2021 Dec TI - Upregulated pigment epithelium-derived factor (PEDF) promotes trophoblast apoptosis and inhibits invasion in preeclampsia. PG - 100576 LID - S1642-431X(21)00097-8 [pii] LID - 10.1016/j.repbio.2021.100576 [doi] AB - Preeclampsia (PE) is a severe pregnancy-specific disorder. Previous findings indicated that pigment epithelium-derived factor (PEDF) was upregulated in placentas of women with PE. Here, we investigated the role of PEDF in trophoblast function, especially under hypoxia. The effects of hypoxia on the morphology of extravillous trophoblast (EVT)-derived HTR-8Svneo cells were observed under inverted microscope. Transfections with Lipofectamine LTX were performed according to the manufacturer's protocol. The expression of PEDF protein and mRNA were confirmed by immunofluorescence (IF) and quantitative real-time PCR (qPCR). Apoptosis was detected by transferase-mediated dUTP nick end labeling (TUNEL) assay, and proliferation of trophoblast was detected by CCK-8 method. The invasion capacity of trophoblast was assessed by Transwell assay. PEDF was expressed in HTR-8/SVneo under both normoxia and hypoxic stress. However, cells of hypoxia groups had higher expression level of PEDF, increased apoptosis and decreased invasion capability, as compared with normoxia group. Moreover, after transfection with plasmid expressing PEDF gene, overexpression of PEDF modulated trophoblast activities. In addition, PEDF expression was negatively associated with invasion while positively correlated with apoptosis.Our data suggest that PEDF is an important factor to maintain the biological function of trophoblast cells, thus representing a rational therapeutic target in PE. CI - Copyright (c) 2021 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved. FAU - Wu, Ying AU - Wu Y AD - Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China. FAU - Chen, Xuexin AU - Chen X AD - Department of Biochemistry and Molecular Biology, GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China. FAU - Jiao, Simeng AU - Jiao S AD - Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China. FAU - Wang, Yiqian AU - Wang Y AD - Department of Biochemistry and Molecular Biology, GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China. Electronic address: you52329@163.com. LA - eng PT - Journal Article DEP - 20211119 PL - Poland TA - Reprod Biol JT - Reproductive biology JID - 101160559 RN - 0 (Eye Proteins) RN - 0 (Nerve Growth Factors) RN - 0 (Serpins) RN - 0 (pigment epithelium-derived factor) RN - S88TT14065 (Oxygen) SB - IM MH - Apoptosis/*drug effects/physiology MH - Cell Line MH - Cell Movement/physiology MH - Eye Proteins/genetics/*metabolism MH - Female MH - Humans MH - Nerve Growth Factors/genetics/*metabolism MH - Oxygen/*pharmacology MH - Pre-Eclampsia/*metabolism MH - Pregnancy MH - Serpins/genetics/*metabolism MH - Trophoblasts/*metabolism OTO - NOTNLM OT - Apoptosis OT - Hypoxia OT - Invasion OT - PEDF OT - Proliferation OT - Trophoblast COIS- Declaration of Competing Interest The authors do not have conflicts of interest to declare. EDAT- 2021/11/23 06:00 MHDA- 2022/02/19 06:00 CRDT- 2021/11/22 20:20 PHST- 2021/09/17 00:00 [received] PHST- 2021/11/03 00:00 [revised] PHST- 2021/11/10 00:00 [accepted] PHST- 2021/11/23 06:00 [pubmed] PHST- 2022/02/19 06:00 [medline] PHST- 2021/11/22 20:20 [entrez] AID - S1642-431X(21)00097-8 [pii] AID - 10.1016/j.repbio.2021.100576 [doi] PST - ppublish SO - Reprod Biol. 2021 Dec;21(4):100576. doi: 10.1016/j.repbio.2021.100576. Epub 2021 Nov 19.