**4. Add on: role of labor on post partum tissue repair**

Since scar defects represent a kind of defect wound healing, we here focus on possible mechanisms which are involved in postpartum tissue repair. As shown in the section "Timing of the CS", there is evidence that an unplanned CS after the onset of labor has advantages concerning niche incidence and further pregnancy complications like uterine rupture and morbidly adherent placenta. Probably, immunological changes which only occur at the time of contractions, may have the potential to contribute to the clinical benefits of a CS after the onset of labor.

The human endometrial tissue holds the capacity to achieve complete regeneration after injures [58]. Particularly, childbirth and the detachment of the deeply invading placenta is generally followed by the restoration of the endometrial layer at the former implantation site. This regeneration is essential for successive pregnancies, as incomplete healing and repair results in endometrium fibrosis or scarring, with potential consequences on the uterine cavity shape or on the adhesiveness and invasiveness of the embryo [59–61]. Despite their relevance, the precise mechanisms of post partum tissue repair and the factors contributing to an impaired endometrial re-epithelialization e.g. after caesarean section remain still poorly described.

To date it is well known that labour entails a series of drastic changes that provoke uterine contractions and birth. This process is characterized by rapid fluctuations in maternal hormones, including the upregulation of glucocorticoids and oxytocin as well as the reduction in progesterone signalling [62, 63]. Simultaneously, there is a shift in the immune responses at the feto-maternal interface from the predominantly anti-inflammatory phenotype throughout pregnancy to a sterile inflammation-like response during labour [64]. This includes inflammasome activation, the release of cytokines and chemokines, and the further recruitment of leukocytes to the feto-maternal interface [65], as studied in detail in relevant animal models.

#### *Prevention of Cesarean Scar Defects: What Is Possible? DOI: http://dx.doi.org/10.5772/intechopen.97618*

In line with this, it is tempting to hypothesize that the effects of labour and uterine contractions may surpass the birth and detachment of the placenta, conveying a central role to the labor-triggered recruitment of immune cells in the machinery of postpartum tissue regeneration. Indeed, the immune system critically orchestrates repair processes in multiple organisms and tissues. Danger signals prompted by tissue injure activate pattern recognition receptors to initiate an immune response [66, 67]. This dynamic response is characterized by the stepwise recruitment of granulocytes, monocytes/macrophages, and T cells [68]. Both recruited and tissue resident leukocytes play scavenger functions and secrete cytokines and growth factors that promote lympho- and angiogenesis, proliferation of tissue cells, and consequently repair [66, 69]. Recently, regulatory T cells have also emerged as important players that ensure regeneration of multiple tissues [70]. Particularly in the case of macrophages and T cells, the balance between inflammatory and anti-inflammatory responses may hold the capacity to tilt the repair process towards scarring or regeneration respectively [68].

Noteworthy, the specific features of the repair process are contingent on the particularities of the tissue affected and little is known about uterine wound healing and prevention of scarring in the postpartum period. In the rodent postpartum uterus, macrophages with an anti-inflammatory M2-like phenotype have been observed in the former implantation sites together with abundant expression of VEGF and its receptors in the uterine stroma and blood vessels that may jointly favour angiogenesis and healing [71, 72]. In contrast, accumulation of M1-like macrophages, neutrophils, and T cells was detected in the uterus of mice exhibiting dysfunctional postpartum uterine repair due to impaired Notch signalling [73]. These findings support that in the uterus, such as in other tissues, an anti-inflammatory milieu is required to prevent the formation of fibrosis upon wound healing. Despite this emerging evidence on the role of immune responses in postpartum tissue healing, further mechanisms and players remain still to be elucidated. In particular, it is still unknown whether labour-induced recruitment of immune cells under the regulatory influence of high levels of steroid hormones contribute to tissue healing, and whether the failure of such a recruitment, e.g. in caesarean deliveries without induction of labour, may hinder endometrial regeneration and result in scar formation.
