Abstract
Objective and DesignThe purpose of the review was to gather information on the role and possibilities of using lipoxin in the treatment of infertility and maintaining a normal pregnancy. Ovulation, menstruation, embryo implantation, and childbirth are reactions representing short-term inflammatory events involving lipoxin activities. Lipoxin A4 (LXA4) is an arachidonic acid metabolite, and in cooperation with its positional isomer lipoxin B4 (LXB4), it is a major lipoxin in mammals. Biosynthesis process occurs in two stages: in the first step, the donor cell releases the eicosanoid intermediate; secondarily, the acceptor cell gets and converts the intermediate product into LXA4 (leukocyte/platelet interaction).ResultsGenerating lipoxin synthesis may also be triggered by salicylic acid, which acetylates cyclooxygenase-2. Lipoxin A4 and its analogues are considered as specialized pro-resolving mediators. LXA4 is an important component for a proper menstrual cycle, embryo implantation, pregnancy, and delivery. Its level in the luteal phase is high, while in the follicular phase, it decreases, which coincides with an increase in estradiol concentration with which it competes for the receptor. LXA4 inhibits the progression of endometriosis. However, during the peri-implantation period, before pregnancy is confirmed clinically, high levels of LXA4 can contribute to early pregnancy loss and may cause miscarriage. After implantation, insufficient LXA4 levels contribute to incorrect maternal vessel remodeling; decreased, shallow trophoblastic invasion; and the immuno-energetic abnormality of the placenta, which negatively affects fetal growth and the maintenance of pregnancy. Moreover, the level of LXA4 increases in the final stages of pregnancy, allowing vessel remodeling and placental separation.MethodsThe review evaluates the literature published in the PubMed and Embase database up to 31 December 2019. The passwords were checked on terms: lipoxin and pregnancy with combined endometriosis, menstrual cycle, implantation, pre-eclampsia, fetal growth restriction, and preterm labor.ConclusionsAlthough no human studies have been performed so far, the cell and animal model study results suggest that LXA4 will be used in obstetrics and gynecology soon.
Highlights
Data on inflammation in diseases is intensively sought at the same time, this process has not been studied in physiological conditions where it is an indispensable factor in the proper course of the menstrual cycle and implantation and delivery
Lipoxin A4 (LXA4) inhibits the progression of endometriosis and, as an endogenous specialized pro-resolving mediators (SPMs) and immunomodulating mediator, is a potentially significant factor in endometriosis development [28, 29]
The PE risk remains at a constant level when aspirin is given after 16 weeks of pregnancy. These results suggest that ASA has a beneficial effect on the pregnancy course until chorion formation is completed, and further ASA administration does not change the course of late pregnancy [40]
Summary
Data on inflammation in diseases is intensively sought at the same time, this process has not been studied in physiological conditions where it is an indispensable factor in the proper course of the menstrual cycle and implantation and delivery. Lipoxin A4 suppresses an increased production of proinflammatory cytokines and alleviates the symptoms of inflammation, contributing to a normal pregnancy course Because both estrogen and progesterone are key hormones in maintaining pregnancy, LXA4 plays a significant role in regulating pregnancy by competing for their common receptor (Fig. 1e). Human placental expression of the lipoxin A4 FPR2/ALX receptor has been demonstrated since the third trimester of gestation; the increased LXA4 level has been observed to be lower when compared to pro-inflammatory cytokines, such as IL-1β and TNF-α [46]. The investigators demonstrated that LXA4 significantly reduced LPS-induced but not the basal expression of pro-inflammatory cytokines IL-6 and IL-8 in human myometrium during pregnancy They suggested that the production or administration of exogenous lipoxins as therapeutic agents could be successful strategies in the prevention of the inappropriate onset of inflammatory pathways resulting in preterm births [102]. The administration of the synthetic 15-epi-lipoxin A4 analogue restored surfactant protein C expression in human fetal lung in a bleomycin-induced pulmonary fibrosis model [106], which supports the hypothesis that lipoxin administration may regulate lung surfactant production
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
