PMID- 35674921 OWN - NLM STAT- MEDLINE DCOM- 20220907 LR - 20220907 IS - 1432-0878 (Electronic) IS - 0302-766X (Linking) VI - 389 IP - 3 DP - 2022 Sep TI - Tanshinone IIA increased amniotic fluid volume through down-regulating placental AQPs expression via inhibiting the activity of GSK-3beta. PG - 547-558 LID - 10.1007/s00441-022-03646-5 [doi] AB - The mechanism of idiopathic oligohydramnios is still uncertain, and there is no effective and targeted treatment for it. Placental aquaporins (AQPs) were associated with idiopathic oligohydramnios. This study aimed to investigate the effect of tanshinone IIA on amniotic fluid volume (AFV) and its underlying molecular mechanisms related to placental AQPs (AQP1, AQP3, AQP8, AQP9). Results showed that compared with the women with normal AFV, placental AQP1, AQP3, AQP8, and AQP9 protein expressions were decreased in women with idiopathic oligohydramnios. Immunohistochemistry revealed localization of AQP1, AQP3, AQP8, and AQP9 mainly in trophoblast cells within labyrinth zone of mouse placenta. Also, AQP1 was located in fetal vascular endothelial cells. Pregnant mice were administered with tanshinone IIA (10 mg/kg or 50 mg/kg, n = 8, respectively) or vehicle (n = 8) from 9.5 to 18.5 gestational day (GD). Tanshinone IIA markedly increased the AFV in pregnant mice, without the effects on embryo numbers per litter, atrophic embryo rate, fetal weight, and placental weight, as well as increased the expressions of AQPs and inhibited the activity of GSK-3beta in mice placenta. In JEG-3 cells, tanshinone IIA downregulated AQP1, AQP3, AQP8, AQP9 expressions and inhibited the activity of GSK-3beta. Activating GSK-3beta with MK-2206 eliminated these alterations. Thus, tanshinone IIA could increase AFV in pregnant mice, possibly through downregulating placental AQP1, AQP3, AQP8, and AQP9 expression via inhibiting the activity of GSK-3beta. Tanshinone IIA may be optional for the treatment of idiopathic oligohydramnios. CI - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Shao, Hailing AU - Shao H AD - Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, 325027, Wenzhou, China. FAU - Pan, Shuangjia AU - Pan S AD - Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, 325027, Wenzhou, China. FAU - Lan, Yehui AU - Lan Y AD - Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, 325027, Wenzhou, China. FAU - Chen, Xianjun AU - Chen X AD - Taizhou Women and Childrens Hospital of Wenzhou Medical University, Taizhou, China. FAU - Dai, Dongru AU - Dai D AD - Department of Obstetrics and Gynecology, The Wenzhou Third Clinical Institute Affiliated To Wenzhou Medical University, Wenzhou, China. FAU - Peng, Lingli AU - Peng L AD - Department of Obstetrics and Gynecology, The Wenzhou Third Clinical Institute Affiliated To Wenzhou Medical University, Wenzhou, China. FAU - Hua, Ying AU - Hua Y AUID- ORCID: 0000-0003-2798-4479 AD - Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, 325027, Wenzhou, China. wzfeyhy1015@126.com. LA - eng GR - 2021KY215/the Project of Zhejiang Province Medical and Health Science and Technology Plan/ GR - Y20210026/the Science and Technology Bureau of Wenzhou/ GR - 2017-XK-A42/the Obstetrics and gynecology of combine traditional Chinese and Western medicine of Zhejiang Province/ PT - Journal Article DEP - 20220608 PL - Germany TA - Cell Tissue Res JT - Cell and tissue research JID - 0417625 RN - 0 (Abietanes) RN - 0 (Aquaporins) RN - 03UUH3J385 (tanshinone) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) SB - IM MH - Abietanes MH - Amniotic Fluid/chemistry/metabolism MH - Animals MH - *Aquaporins/metabolism MH - Cell Line, Tumor MH - Endothelial Cells/metabolism MH - Female MH - Glycogen Synthase Kinase 3 beta/metabolism MH - Humans MH - Mice MH - *Oligohydramnios/metabolism MH - Placenta/metabolism MH - Pregnancy OTO - NOTNLM OT - Aquaporin OT - Glycogen synthetic kinase 3beta OT - Oligohydramnios OT - Placenta OT - Tanshinone IIA EDAT- 2022/06/09 06:00 MHDA- 2022/09/08 06:00 CRDT- 2022/06/08 11:20 PHST- 2021/10/28 00:00 [received] PHST- 2022/05/27 00:00 [accepted] PHST- 2022/06/09 06:00 [pubmed] PHST- 2022/09/08 06:00 [medline] PHST- 2022/06/08 11:20 [entrez] AID - 10.1007/s00441-022-03646-5 [pii] AID - 10.1007/s00441-022-03646-5 [doi] PST - ppublish SO - Cell Tissue Res. 2022 Sep;389(3):547-558. doi: 10.1007/s00441-022-03646-5. Epub 2022 Jun 8.