This study determined whether a progesterone (P) receptor (PR)-mediated mechanism regulates morphological characteristics associated with prepartum cervix remodeling at term and with preterm birth. With focus on the transition from a soft to ripe cervix, the cervix stroma of untreated controls had reduced cell nuclei density/area and less organized extracellular collagen, while the density of macrophages/area, but not neutrophils, increased just 2 days before birth (day 17 vs day 15 or 16.5 postbreeding). Preterm birth was induced within 24 hours of treatment on day 16 postbreeding with PR antagonist or ovariectomy (Ovx). Pure or mixed PR antagonists increased the density of macrophages in the cervix within 8 hours (day 16.5 postbreeding), in advance of preterm birth. However, neither PR antagonists nor P withdrawal after Ovx affected the densities of cell nuclei and neutrophils or extracellular collagen compared to the same day controls-an indication that the cervix was sufficiently remodeled for birth to occur. To block the effect of systemic P withdrawal, Ovx pregnant mice were given a PR agonist, either pure or mixed. These treatments forestalled preterm birth and prevented further morphological remodeling of the cervix. The resulting increase in macrophage density in cervix stroma following Ovx was only blocked by a pure PR agonist. These findings support the hypothesis that inflammatory processes in the prepartum cervix that include residency of macrophages, cellular hypertrophy, and extracellular collagen structure are regulated by genomic actions of PR in a final common mechanism both at term and with induced preterm birth.

To test the hypothesis that macrophages are essential for remodeling the cervix in preparation for birth, pregnant homozygous CD11b-dtr mice were injected with diphtheria toxin (DT) on days 14 and 16 postbreeding. On day 15 postbreeding, macrophages (F4/80+) were depleted in cervix and kidney, but not in liver, ovary, or other non-reproductive tissues in DT—compared to saline—treated dtr mice or wild-type controls given DT or saline. Within 24 h of DT-treatment, the density of cell nuclei and macrophages declined in cervix stroma in dtr mice versus controls, but birefringence of collagen, as an indication of extracellular cross-linked structure, remained unchanged. Only in the cervix of DT-treated dtr mice was an apoptotic morphology evident in macrophages. DT-treatment did not alter the sparse presence or morphology of neutrophils. By day 18 postbreeding, macrophages repopulated the cervix in DT-treated dtr mice so that the numbers were comparable to that in controls. However, at term, evidence of fetal mortality without cervix ripening occurred in most dtr mice given DT—a possible consequence of treatment effects on placental function. These findings suggest that CD11b+ F4/80+ macrophages are important to sustain pregnancy and are required for processes that remodel the cervix in preparation for parturition.

Since 2010, Ohio legislators have passed more than 15 legislative changes related to abortion and abortion providers, and nine procedural abortion clinics have closed.We investigated reproductive genetic counselors' perceptions, attitudes and selfreported practices regarding Ohio's current and proposed abortion regulations. We conducted five focus groups and two telephone interviews in 2019-2020, with a total of 19 reproductive genetic counselors. Participants discussed difficulties keeping current on abortion legislation and clinics' and hospitals' policies, resulting in anticipatory anxiety and leading to additional work to discuss the laws with patients.Participants articulated that practices of reproductive genetic counseling-and patient advocacy-are impeded by the legislation. Genetic counselors perceive negative impacts on patients' autonomy, particularly reflective of healthcare disparities of marginalized groups, which may contribute to frustration and anger. Ultimately, the mental and emotional burden on genetic counselors created by abortion legislation contributes to compassion fatigue and burnout. Our findings show that Ohio's abortion regulations negatively impact reproductive genetic counselors and their relationships with their patients. Repealing existing abortion regulations and preventing future restrictive legislation may ameliorate the negative effects of regulations on reproductive genetic counselors and their patients. In the event that these laws remain, innovative communication tools and proactive professional society advocacy are potential means to mitigate the negative impact on reproductive genetic counselors.

The prepartum transition from a soft to ripening cervix is an inflammatory process that occurs well before birth when systemic progesterone is near peak concentration. This 2-part study first determined that stromal fibroblasts but not macrophages in the cervix have progesterone receptors (PRs). Neither the number of PR cells in cervix sections nor the relative abundance or ratio of nuclear PR isoforms (PR-A/PR-B) were diminished in mice between day 15 of pregnancy and term. Second in mice lacking PR-B (Pgr tm20mc), the number of cells that expressed the PR-A isoform were maintained during this period of prepartum cervix remodeling. Thus, progesterone effects to sustain pregnancy, as well as soften and ripen the cervix, are mediated by a stable stromal cell population that expresses PR-A and, through interactions with resident macrophages, are likely to mediate inflammatory ripening processes in preparation for birth.