An increased proportion of progesterone receptor A in peripheral B cells from women who ultimately underwent spontaneous preterm birth

Progesterone (P4) is involved in the establishment and maintenance of pregnancy (Arrowsmith et al., 2010) and supports immune tolerance towards to the semiallogeneic fetus (Robinson and Klein, 2012). The P4 level in plasma rises gradually until about 32 weeks of gestation (Kumar and Magon, 2012), followed by a “functional P4 withdrawal” in uterine tissues. One important mechanism therefore is mediated by altering the expression levels of P4 receptor (PR) isoforms, PR-A and PR-B (Merlino et al., 2009, Wen et al., 1994, Kastner et al., 1990). In pregnancy, myometrial quiescence is mediated by PR-B, labor is associated with an increased PR-A to PR-B ratio that results in an increased expression of pro-labor genes (Tan et al., 2012).

PRs are also expressed by T cells, which enable them to respond to P4 (Chiu et al., 1996, Areia et al., 2016, Szekeres-Bartho et al., 2001). Ligation of P4 to its receptor on T cells might suppress their activation during pregnancy (Chien et al., 2007), proliferation and secretion of inflammatory cytokines (Lissauer et al., 2015).

B cells express PR, predominantly PR-A (Bommer et al., 2016). Stimulation of B cells and B regulatory cells (Breg) with P4 induced IL-10 (Muzzio et al., 2014, Esteve-Sole et al., 2018) and the production of asymmetric, protective antibodies (Canellada et al., 2002). We have shown that the Breg cell population expands in normal pregnant women (Rolle et al., 2013). Interestingly, in the occurrence of preterm birth (PTB), their frequency was reduced and instead a shift towards inflammatory B cells was observed (Busse et al., 2020, Busse et al., 2021). However, the expression of PR in these cells has not been studied.

PTB, the delivery of a living baby before 37 weeks of gestation, might be spontaneous or medically indicated. Each year, about 15 million babies are born premature worldwide (Walani, 2020). Therefore, prematurity is one of the biggest problems in obstetrics and a common cause of newborn death and long-term morbidity in children (Blencowe et al., 2013).

Currently, there is no test that reliably predicts PTB for women diagnosed for imminent PTB. In most women that were admitted to hospital with preterm labor (PTL), labor can be stopped and delivery averted. Since these women are still at a high risk for PTB, a maintenance tocolytic agent such as vaginal P4 might help to further prevent PTB (Suhag et al., 2015, Romero et al., 2018), although the exact mode of action is unknown. Therefore, there is an urgent need to identify mechanisms underlying the treatment with P4.

In this study, we investigated the PR expression by B cells in PTB compared to term birth. Moreover, we addressed the question whether PR expression by B cells could serve as a marker to identify women that will deliver preterm from women that will not give birth preterm following admission to hospital with signs of PTL.

留言 (0)

沒有登入
gif