Inflammatory Pathologies in Reproductive Tract: Role of NETs and METs on Fertilization Disorders

The role of neutrophil extracellular traps (NETs) and monocyte extracellular traps (METs) is well established in fertilization disorders by adverse effects on sperm motility, acrosome integrity, membrane lipoperoxidation, and disturbing oocyte sperm binding. Moreover, NETs/METs remove efficiently excessive spermatozoa within the female reproductive tract (FRT) after natural coitus or artificial insemination (AI). Depending on their location in reproductive organs, NETs/METs may be beneficial to the host by their capability of either limiting the dissemination of infective pathogens, promoting wound healing, and exerting anti-inflammatory properties through the degradation of pro-inflammatory components. Conversely, excessive or imbalanced NETs/METs release within FRT or urogenital tract (UGT) might be associated with worse fertility due to deleterious effects on sperm functions, oocyte fertilization, endometrium microenvironment, and embryo implantation. In the UGT, patients with epididymitis or urogenital bacterial infections and with leukocytospermia spontaneous release of NETs/METs in seminal fluids. Moreover, in infertile male/female patients without infectious etiologies but with autoimmune (i. e. systemic lupus erythematosus, rheumatoid arthritis)-, metabolic (diabetes mellitus, obesity)- and vascular (vasculitis, hypertension, and preeclampsia)- diseases uncontrolled NETs/METs might negatively influence their fertility. Thus, this review aims to provide novel insights into the beneficial as well as adverse effects of NETs/METs on male gametes, oocyte fertilization, and endometrium by highlighting broad implications on early diagnosis of extracellular traps (ETs) in seminal fluid samples of infertility patients with inflammatory etiologies. As well as, for early diagnosis of spontaneous formation of NETs/METs in infertile couples with one or both being affected with chronic inflammatory-, metabolic-, vascular- and/or autoimmune diseases to increase the chance of conception.