Abstract
Aquaporins (AQPs) are expressed in the uterus, playing a physiological role during pregnancy. An osmotic pathway—through AQP5—may modify the transient potential vanilloid 4 (TRPV4) function and uterine contraction. Our aim was to determine the role of TRPV4 antagonist citral in the regulation of pregnant uterine contraction. In vitro uterine contractions were evoked by KCl and the response was modified with citral. The expressions of TRPV4 and AQP5 were measured by RT-PCR and Western blot techniques. The lengths of gestational periods were determined in normal and LPS-induced preterm births after citral treatment, in vivo. Citral significantly decreased the uterine contraction on day 22 of pregnancy. AQP5 expression significantly increased after citral incubation; however, TRPV4 expression did not show significant changes. After citral pretreatment, the gestational period was extended both in normal and LPS-induced preterm births. Our results suppose that the downregulation of AQP5 may initiate hypertonic stress, activating TRPV4 the uterine contraction on the last day of the gestational period. The putative cooperation between AQP5 and TRPV4 may open a novel target to treat or prevent preterm birth.
Highlights
Aquaporins (AQPs) are crucial for water and small solute transport across physiological barriers
AQP5 expression was found to be predominant during pregnancy in rats, it was significantly downregulated at the last gestational day
The animals were divided into 6 groups (n = 6–8): (1) intact pregnant rats on day 22 of pregnancy; (2) pregnant rats, orally treated with olive oil, as a vehicle control, on days 18–22 once daily; (3) pregnant rats, orally treated with citral (240 mg/kg [3], administered by oral gavage; in olive oil vehicle; Sigma-Aldrich, Budapest, Hungary) on days 18–22 once daily; (4) pregnant rats treated with LPS (50 μg/animal, intraperitoneally; Sigma Aldrich, Hungary) on day 18 of pregnancy to induce preterm birth on day 20 [16]; and (5) pregnant rats treated with LPS on day 18 and citral on days 18–22 once daily
Summary
Aquaporins (AQPs) are crucial for water and small solute transport across physiological barriers. AQPs play role during gestational period including parturition, myometrial contractility, and cervical ripening [2]. AQP5 expression was found to be predominant during pregnancy in rats, it was significantly downregulated at the last gestational day. AQP5 was upregulated by oxytocin [3] and its expression was estrogen and progesterone dependent in the uteri of late-term rats [4]. It is supposed that at the end of pregnancy the intensity of the uterine contractions has an inverse correlation with the expression of the uterine AQP5. The TRP subfamily transient receptor potential vanilloid (TRPV) channels are permeable to calcium, magnesium, and sodium [6]. As the prominent co-localization of TRPV4 and AQP4 in retinal Müller glia cells was earlier identified (registration number: IV/2767/2020). T1.hTehseumsummamryaroyf othfetheexpexerpiemriemnteanltmalomdeoldfeolrfothrethceitrcaitlr‐atrle-tarteeadterdatrsa. tAs.ftAerfttehrethtreetartematemntesn, ts, aniamnaimlsawlsewreeirnevinolvvoeldvebdotbhotihntiontino ivnitvroitraondanidn ivnivvoivsotusdtuiedsi.es
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