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This chapter initially provides a brief overview of current knowledge of neutrophil biology, providing background knowledge. It then examines neutrophil contributions to endometrial remodeling during the normal menstrual cycle, menstruation, and subsequent endometrial repair. This is followed by discussion of what is known of neutrophil contributions to placental development, parturition, and maternal immunotolerance. Finally, it examines how disturbances in neutrophil trafficking and phenotype may contribute to disorders such as abnormal uterine bleeding, pre-eclampsia, antiphospholipid syndrome and preterm birth. Importantly, the chapter highlights that while neutrophils predominantly act in concert with other immune cell types as part of the inflammatory cascade, neutrophils also perform specific independent physiological processes within the female reproductive tract. These independent processes are facilitated via release of inflammatory mediators, proteases, extracellular vesicles, and neutrophil traps released into the local tissue microenvironment, which interact with a variety of nonimmune cell types within the local milieu.

Menstruation is the process by which the functionalis layer of the endometrium is shed and restored during each menstrual cycle in women, without scarring or loss of function. The trigger for menstruation is withdrawal of hormonal support in a nonconception cycle, which induces highly controlled inflammatory mechanisms starting with influx and activation of specific leukocyte subsets and release of bioactive mediators, including degradative enzymes. Tissue breakdown and repair occur simultaneously in different/adjacent areas of the tissue. Re -epithelialization rapidly covers the degraded surface, independently of hormone (estrogen) support: full regeneration of the endometrial functionalis follows with estrogen support during the ensuing proliferative phase.

The human endometrium undergoes extensive remodelling during the menstrual cycle in preparation of a favorable environment for implantation. Biphasic fluctuations of hyaluronan (HA) in the cycling endometrium have been demonstrated with peaks occurring during the early proliferative (days 6–8) and mid secretory (days 19–23) stages of the cycle. The second, mid secretory, HA peak encompasses the time of embryo implantation suggesting a possible role for HA in this process. The aim of the present study was to investigate expression patterns of the 3-hyaluronan synthase (HAS) isoforms: HAS-1, HAS-2 and HAS-3. In situ hybridization was carried out on formalin fixed endometrial tissue across the cycle to determine whether these enzymes were expressed in human endometrium and if so, their cellular source. Riboprobes were constructed for each HAS: HAS-1 (64bp), HAS-2 (60bp) and HAS-3 (550bp) and labeled with digoxygenin (DIG). The HAS protein was also localized immunohistochemically using a polyclonal antibody against extracellular HAS peptides. All three forms of HAS mRNA were expressed in the human endometrium. Expression was observed in both stromal and glandular epithelial cells with greatest intensity in epithelial cells and considerable cyclical changes. In all cases expression of mRNA was low during menstruation (days 1–5). Levels increased throughout the proliferative stage (days 6–14) of the cycle and for HAS-2 and HAS-3 remained elevated until the mid secretory (days 19–23) / implantation phase. HAS-1 expression temporarily decreased during the late proliferative stage (days 12–14). Following implantation expression of all HAS types decreased dramatically. HAS protein localization was demonstrated on the plasma membrane of both glandular epithelial and stromal cells. The partial correlation between HA and HAS supports a role for these enzymes in endometrial HA regulation during the menstrual cycle and also suggests tight control of enzyme expression.