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  • br Introduction Melatonin mainly originates from

    2019-07-09


    Introduction Melatonin mainly originates from the pineal gland (Reiter, 1991) and is well known for its physiological functions in the regulation of circadian rhythms (Cajochen et al., 2003) and as a potent free radical scavenger and broad-spectrum antioxidant in mammals (Paradies et al., 2010, Tan et al., 2007). Many physiological functions of melatonin are modulated through two types of melatonin membrane receptors (MRs), namely MT1 and MT2, and both of these are present in reproductive organs (Slominski et al., 2012). It has been demonstrated that melatonin is involved in modulating steroidogenesis (Sirotkin and Schaeffer, 1997), follicular development (Rocha et al. 2013), oocyte maturation (Tian et al., 2015; Sanghoon et al., 2018), ovulation (Reiter et al., 2013), and luteinization (He et al., 2016) via its receptor pathway in the ovary. Moreover, functional MT1 and MT2 receptors have also been detected in the uterus of many species (Schlabritzloutsevitch et al., 2003, Zhao et al., 2002, Huo et al., 2015), and these are involved in regulating decidualization (Zhao et al., 2002), embryo implantation (He et al., 2015), and myometrium contractility (Ayar et al., 2001, Sharkey et al., 2009). These studies suggest that melatonin and its receptors play an important role in reproduction (Talpur et al., 2018). It has been demonstrated that the expression of MT1 and MT2 differs in pregnant and non-pregnant uteri in humans (Schlabritzloutsevitch et al., 2003) and yaks (Huo et al., 2015). Moreover, melatonin binding in the rat uterus fluctuates during the estrous cycle, and is lowest during metestrus; it was also demonstrated that MT1 in the rat antimesometrial stroma is regulated by ovarian hormones (Zhao et al., 2002). In addition, Clemens et al. (2001) found that E2 induces a significant decrease in melatonin binding to ovarian membranes, in addition to the down-regulation of MT1 in rat ovaries in vivo. Although there are no reports concerning the effect of E2 on MT2, these studies suggest that it might be involved in the regulation of MR pathways. Ovarian steroid hormone estrogens, particularly estradiol (E2), play important roles in the regulation of reproductive functions. E2 is mainly synthesized and secreted by granulosa Ranitidine in antral follicles, especially preovulatory dominant follicles (Dieleman and Bevers, 1987). Further, sheep pre-ovulation follicular fluid contains much higher levels of E2 than serum, approximately 1 µg/ml (Tetsuka and Nancarrow, 2007), and upon ovulation, the luminal side (apical compartment) of the oviduct epithelium is temporarily exposed to follicular fluid (Palma-Vera et al., 2017). The location of MRs in the rat oviduct has been demonstrated (Chuffa et al., 2011, 2013). However, there are no reports regarding the expression of MT1 and MT2 in the sheep oviduct and whether these receptors are regulated by E2. The oviduct in mammals plays a critical and functional role in reproduction, including transport of the ova and spermatozoa and development of the pre-implantation conceptus, in addition to serving as an environment for gametes and embryos (Gandolfi, 1995) and the site of fertilization and early embryonic development. Given the lack of information regarding the expression of MRs in the sheep oviduct, and to further elucidate the E2-mediated regulatory mechanism, the objective of this work was to assess the presence of MT1 and MT2 in the sheep oviduct and evaluate their expression patterns in the ovulating and non-ovulating sides of the oviduct in the sheep ampulla and isthmus. In vitro, we also used E2 and ICI182780 (a non-selective estrogenreceptor antagonist) to treat cultured oviduct epithelial cells to determine the mechanism through which E2 affects MR expression.
    Material and methods
    Results
    Discussion Melatonin receptors mediate the role of melatonin to regulate certain biological functions. In this study, we found that both MT1 and MT2 are expressed in the sheep oviduct. These results were similar to those found using rats (Chuffa et al., 2011, 2013), which suggested that the oviduct is also a target tissue that is regulated by melatonin. Previous studies have demonstrated that melatonin affects steroidogenesis through MT1 and MT2 receptors in the female reproductive tract (Woo et al., 2015). Moreover, MRs are also involved in the release of growth factors such as IGF-I (Picinato et al., 2010). Further, oviduct epithelial cells have a secretory function, which can result in the de novo synthesis and release of molecules such as lipids, enzymes, and growth factors into the oviduct lumen (Henault and Killian, 1993; Killian, 1997) to offer nutrition to the conceptus, in addition to contributing to sperm binding, gamete growth, and developmental regulation (Gandolfi, 1995). The primary location of MT1 and MT2 in the oviduct luminal epithelial cell layer might indicate that melatonin is involved in the regulation of the secretion of oviductal epithelial cells and the maintenance of the oviduct environment.