Exposure to Progestin 17-OHPC Induces Gastrointestinal Dysfunction through Claudin 1 Suppression in Female Mice with Increased Anxiety-Like Behaviors.

INTRODUCTION: Progestin, commonly used in oral contraception and preventing preterm birth, elicits various off-target side effects on brain and gastrointestinal (GI) functions, yet the precise mechanisms remain elusive. This study aims to probe progestin's impact on GI function and anxiety-like behaviors in female mice. METHODS: Colon stem cells were utilized to explore the mechanism underlying progestin 17-hydroxyprogesterone caproate (17-OHPC)-mediated suppression of claudin-1 (CLDN1), crucial for epithelial integrity. Chromatin immunoprecipitation and luciferase assays identified potential progestin-response elements on the CLDN1 promoter, with subsequent assessment of oxidative stress and pro-inflammatory cytokine release. Manipulation of vitamin D receptor (VDR) or estrogen receptor ß (ERß) expression elucidated their roles in 17-OHPC-mediated effects. Intestine-specific VDR deficient mice were generated to evaluate 17-OHPC's impact on GI dysfunction and anxiety-like behaviors in female mice. Additionally, gene expression was analyzed in various brain regions, including the amygdala, hypothalamus, and hippocampus. RESULTS: Exposure to 17-OHPC suppressed CLDN1 expression via epigenetic modifications and VDR dissociation from the CLDN1 promoter. Furthermore, 17-OHPC intensified oxidative stress and proinflammatory cytokine release. VDR knockdown partly mimicked, while overexpression of either VDR or ERß partly restored 17-OHPC-mediated effects. Intestinal VDR deficiency partly mirrored 17-OHPC-induced GI dysfunction, with minimal impact on 17-OHPC-mediated anxiety-like behaviors. CONCLUSIONS: 17-OHPC suppresses CLDN1 expression through VDR, contributing to GI dysfunction in female mice, distinct from 17-OHPC-induced anxiety-like behaviors. This study reveals a new mechanism and potential negative impact of progestin exposure on the gastrointestinal tract, alongside inducing anxiety-like behaviors in female mice.

Effect of minimally invasive surgery and laparotomy on wound infection and postoperative and intraoperative complications in the management of cervical cancer: A meta-analysis.

We performed a meta-analysis to evaluate the effect of minimally invasive surgery and laparotomy on wound infection and postoperative and intraoperative complications in the management of cervical cancer. A systematic literature search up to July 2022 was performed and 10 231 subjects with cervical cancer at the baseline of the studies; 4307 of them were using the minimally invasive surgery, and 5924 were using laparotomy. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of minimally invasive surgery and laparotomy on wound infection and postoperative and intraoperative complications in the management of cervical cancer using the dichotomous methods with a random or fixed-effect model. The minimally invasive surgery had significantly lower wound infection (OR, 0.20; 95% CI, 0.13-0.30, P < .001), and postoperative complications (OR, 0.48; 95% CI, 0.37-0.64, P < .001) in subjects with cervical cancer compared laparotomy. However, minimally invasive surgery compared with laparotomy in subjects with cervical cancer had no significant difference in intraoperative complications (OR, 1.04; 95% CI, 0.80-1.36, P = 0.76). The minimally invasive surgery had significantly lower wound infection, and postoperative complications however, had no significant difference in intraoperative complications in subjects with cervical cancer compared with laparotomy. The analysis of outcomes should be with caution because of the low sample size of 22 out of 41 studies in the meta-analysis and a low number of studies in certain comparisons.