Inflammation with the participation of arachidonic (AA) and linoleic acid (LA) derivatives (HETEs and HODEs) is necessary in the course of a normal reproductive cycle and pregnancy

J Reprod Immunol. 2020 Sep:141:103177. doi: 10.1016/j.jri.2020.103177. Epub 2020 Jul 7.

Abstract

Data on arachidonic (AA) and linoleic (LA) acid derivatives and their role in the reproductive cycle are limited. In order to systematize these reports, 54 scientific investigations were analyzed, which revealed the important role of AA and LA in the planning and course of pregnancy. Ovulation, menstruation, pregnancy, and childbirth are strongly related to the occurrence of physiological inflammatory reactions. Ovulation and menstruation are cyclic tissue remodeling processes that cause changes in the synthesis of inflammation mediators, such as prostaglandins and leukotrienes. Thus, the cyclooxygenase (COX) and lipoxygenase-5 (5-LOX) pathway for AA transformation is activated. Only the absence of neutrophils during this process differentiates an embryo implantation from a standard inflammatory response. It has been found that in COX-2 deficiency conditions, incorrect embryo implantation and decidual reaction occur; therefore, the mechanism associated with the activation of the nuclear factor (NF)-κB pathway seems to play an important role in the course of embryo implantation. In addition, 12/15-LOX may be key modulators of uterine activity during the implantation process. According to the current state of knowledge, AA derivatives synthesized throughout the cytochrome P450 (CYP) and LOX pathways play a special role in the late pregnancy period. Decreased 5-HETE levels have been related to slowing down the progression of labor, while 11-HETE and 15-HETrE to its acceleration. It has been also proven that renal 20-HETE contents undergo significant changes in the late pregnancy period, which are caused by an increase in their adrenal medulla and vascular synthesis, leading to decrease of blood pressure and an increase of sodium excretion, finally conditioning a normal course of labor.

Keywords: HETE; HODE; Inflammation; Menstrual cycle; Pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amniotic Fluid / immunology
  • Amniotic Fluid / metabolism
  • Animals
  • Arachidonate 5-Lipoxygenase / metabolism
  • Embryo Implantation / immunology
  • Endometrium / immunology
  • Endometrium / metabolism
  • Female
  • Humans
  • Hydroxyeicosatetraenoic Acids / metabolism*
  • Inflammation / immunology*
  • Linoleic Acids / metabolism*
  • Models, Animal
  • Pregnancy / immunology*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Signal Transduction / immunology*

Substances

  • Hydroxyeicosatetraenoic Acids
  • Linoleic Acids
  • Arachidonate 5-Lipoxygenase
  • Prostaglandin-Endoperoxide Synthases