ProblemExcisional surgery for cervical intraepithelial neoplasia is a risk factor for preterm birth in subsequent pregnancies. However, the underlying mechanisms of this association remain unclear. We previously showed that cervical MUC5B, a mucin protein, may be a barrier to ascending pathogens during pregnancy. We thus hypothesized that hyposecretion of cervical MUC5B is associated with preterm birth after cervical excisional surgery.Method of studyThis prospective nested case‐control study (Study 1) included pregnant women who had previously undergone cervical excisional surgery across 11 hospitals. We used proteomics to compare cervicovaginal fluid at 18–22 weeks of gestation between the preterm and term birth groups. In another case‒control analysis (Study 2), we compared MUC5B expression in nonpregnant uterine tissues between 15 women with a history of cervical excisional surgery and 26 women without a history of cervical surgery.ResultsThe abundance of MUC5B in cervicovaginal fluid was significantly decreased in the preterm birth group (fold change = 0.41, p = .035). Among the 480 quantified proteins, MUC5B had the second highest positive correlation with gestational age at delivery in the combined preterm and term groups. The cervicovaginal microbiome composition was not significantly different between the two groups. Cervical length was not correlated with gestational age at delivery (r = 0.18, p = .079). Histologically, the MUC5B‐positive area in the nonpregnant cervix was significantly decreased in women with a history of cervical excisional surgery (0.85‐fold, p = .048). The distribution of MUC5B‐positive areas in the cervical tissues of 26 women without a history of cervical excisional surgery differed across individuals.ConclusionsThis study suggests that the primary mechanism by which cervical excisional surgery causes preterm birth is the hyposecretion of MUC5B due to loss of the cervical glands.

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宫颈MUC5B分泌不足与宫颈切除术后孕妇早产相关

问题宫颈上皮内瘤变的切除手术是随后妊娠中早产的危险因素。然而，这种关联的潜在机制仍不清楚。我们之前表明，宫颈MUC5B（一种粘蛋白）可能是妊娠期间病原体上行的屏障。因此，我们假设宫颈 MUC5B 分泌不足与宫颈切除手术后的早产有关。 研究方法这项前瞻性巢式病例对照研究（研究 1）纳入了 11 家医院之前接受过宫颈切除手术的孕妇。我们使用蛋白质组学来比较早产组和足月组妊娠 18-22 周时的宫颈阴道液。在另一项病例对照分析（研究 2）中，我们比较了 15 名有宫颈切除手术史的女性和 26 名无宫颈手术史的女性的非妊娠子宫组织中 MUC5B 的表达。结果早产组（倍数变化 = 0.41，p= .035)。在 480 种定量蛋白质中，MUC5B 与早产儿组和足月儿组的分娩胎龄呈第二高的正相关性。两组之间的宫颈阴道微生物组组成没有显着差异。宫颈长度与分娩时的胎龄不相关（r= 0.18,p=.079）。组织学上，有宫颈切除手术史的女性非妊娠子宫颈中的 MUC5B 阳性区域显着减少（0.85 倍，p=.048）。26 名无宫颈切除手术史的女性的宫颈组织中 MUC5B 阳性区域的分布存在个体差异。结论本研究表明，宫颈切除手术导致早产的主要机制是由于 MUC5B 缺失而导致的 MUC5B 分泌不足。宫颈腺。