Ureaplasma spp., commonly identified in the vagina/cervix of pregnant women with spontaneous preterm delivery, are the most frequently detected microorganisms in amniotic fluid. To date, 14 U. spp. serotypes have been characterized; however, modern molecular biology methods can distinguish different U. spp genotypes. Considering these factors, a knowledge gap exists regarding the association between U. spp. genotypes and the risk of the ascension of U. spp. from the cervix to the amniotic cavity. To fill this gap, an expanded multilocus sequence-typing scheme of U. spp. was performed to assess the relationship between cervical and amniotic fluid U. spp. in pregnant women with spontaneous preterm delivery. This study included 109 and 69 pregnant women with spontaneous preterm labor (PTL) and preterm prelabor rupture of membranes (PPROM), respectively. U. spp. DNA in cervical fluid was identified in 49% and 55% of the women with PTL and PPROM, respectively. The concurrent presence of U. spp. DNA in amniotic fluid was observed in 17% and 59% of the pregnant women with PTL and PPROM, respectively. Among pregnant women with PTL and PPROM, 38 expanded sequence types of cervical U. spp. were identified. No associations were observed between specific genotypes, subgroups, or clusters of cervical U. spp. and the presence of amniotic fluid U. spp. in pregnant women with spontaneous preterm delivery.

• Klíčová slova
• Amniotic fluid, Genital mycoplasmas, Invasive sampling, Non-invasive sampling, Preterm birth,
• MeSH
• cervix uteri * mikrobiologie   MeSH
• DNA bakterií genetika   MeSH
• dospělí MeSH
• genotyp MeSH
• infekční komplikace v těhotenství mikrobiologie   MeSH
• lidé MeSH
• mladý dospělý MeSH
• multilokusová sekvenční typizace MeSH
• plodová voda mikrobiologie   MeSH
• předčasná porodní činnost mikrobiologie   MeSH
• předčasný odtok plodové vody mikrobiologie   MeSH
• předčasný porod * mikrobiologie   MeSH
• těhotenství MeSH
• Ureaplasma * genetika   izolace a purifikace   klasifikace   MeSH
• ureaplasmatické infekce * mikrobiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA bakterií MeSH

Preterm, prelabor rupture of the human fetal membranes (pPROM) is involved in 40% of spontaneous preterm births worldwide. Cellular-level disturbances and inflammation are effectors of membrane degradation, weakening, and rupture. Maternal risk factors induce oxidative stress (OS), senescence, and senescence-associated inflammation of the fetal membranes as reported mechanisms related to pPROM. Inflammation can also arise in fetal membrane cells (amnion/chorion) due to OS-induced autophagy and epithelial-mesenchymal transition (EMT). Autophagy, EMT, and their correlation in pPROM, along with OS-induced autophagy-related changes in amnion and chorion cells in vitro, were investigated. Immunocytochemistry staining of cytokeratin-18 (epithelial marker)/vimentin (mesenchymal marker) and proautophagy-inducing factor LC3B were performed in fetal membranes from pPROM, term not in labor, and term labor. Ultrastructural changes associated with autophagy were verified by transmission electron microscopy of the fetal membranes and in cells exposed to cigarette smoke extract (an OS inducer). EMT and LC3B staining was compared in the chorion from pPROM versus term not in labor. Transmission electron microscopy confirmed autophagosome formation in pPROM amnion and chorion. In cell culture, autophagosomes were formed in the amnion with OS treatment, while autophagosomes were accumulated in both cell types with autophagy inhibition. This study documents the association between pPROMs and amniochorion autophagy and EMT, and supports a role for OS in inducing dysfunctional cells that increase inflammation, predisposing membranes to rupture.

• MeSH
• autofagie MeSH
• epitelo-mezenchymální tranzice MeSH
• extraembryonální obaly * metabolismus   MeSH
• lidé MeSH
• novorozenec MeSH
• předčasný odtok plodové vody * metabolismus   MeSH
• zánět patologie   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Human fetal membranes (amniochorion) that line the intrauterine cavity consist of two distinct cell layers; single-layer amnion epithelial cells (AEC) and multilayer chorion trophoblast cells (CTC). These layers are connected through a collagen-rich extracellular matrix. Cellular remodeling helps support membrane growth and integrity during gestation and helps to maintain pregnancy. Preterm prelabor rupture of the human amniochorionic (fetal) membrane (pPROM) is antecedent to 40% of all spontaneous preterm birth. Oxidative stress (OS) induced activation of the p38 MAPK due to various maternal risk exposures and the amniochorion cells' senescence are reported pathological features of pPROM. Our transcriptomics analysis implicated dysregulated autophagy and epithelial-mesenchymal transition (EMT) in fetal membranes from pPROM. The molecular interplay between OS-induced p38 MAPK activation, autophagy, and EMT was investigated in AECs and CTCs to better understand the involvement of autophagy and EMT. We report the differential impact of OS on the autophagic machinery in AECs and CTCs, resulting in distinct cell fates. In AECs, OS-induced p38 MAPK activation causes autophagosome accumulation and reduced autophagic flux mediated by decreased ULK1 activity and kinase activity, leading to senescence. In CTCs, induction of autophagy has a limited effect; however, inhibition of autophagy led to SQSTM1-mediated EMT of trophoblast cells. Autophagy, EMT, and senescence were associated with proinflammatory changes. Thus, AECs and CTCs respond differently to OS via differential autophagy response, partly mediated via p38 MAPK. Besides senescence, OS-induced autophagy dysregulation in amniochorion cells may play a mechanistic role in pPROM pathophysiology.

• Klíčová slova
• Membrane rupture, Oxidative stress, amnion, autophagy, chorion, epithelial-mesenchymal transition, p38 MAPK, preterm birth, preterm premature rupture of membranes, senescence, trophoblast,
• Publikační typ
• časopisecké články MeSH