Placental inflammation and viral infection are implicated in second trimester pregnancy loss

Srinivas, Sindhu K.; Ma, Yujie; Sammel, Mary D.; Chou, Doris; McGrath, Cindy; Parry, Samuel; Elovitz, Michal A.

doi:10.1016/j.ajog.2006.05.049

Cited by 129 publications

(104 citation statements)

References 20 publications

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“…Histopathological features were within those accepted as normal on H&E. That this group was associated with acute chorioamnionitis is consistent with a second trimester study wherein PCR identified HPV DNA more frequently in acute chorioamnionitis than in controls. 7 Furthermore, cervical HPV infection impairs the physiological protective capacity of the uterine cervix. 30 Studies employing in situ hybridization have detected HPV DNA in non-neoplastic endometrium in 19.6 31 and 60% 32 of biopsies.…”

Section: Discussionmentioning

confidence: 99%

“…The most common and important neoplastic driver of the lower uterine tract, human papillomavirus (HPV), 1 has been detected in the uterine cervix of 15-25% of pregnant women [2][3][4][5][6] and a cervical HPV infection during pregnancy has been associated with a higher incidence of spontaneous abortions, [7][8][9] premature rupture of the membranes, 10 spontaneous preterm labor, 11,12 pre-eclampsia, 13 and placental 'villitis' not otherwise specified. 12 HPV DNA has been detected in the placenta and amniotic fluid.…”

mentioning

confidence: 99%

“…12 HPV DNA has been detected in the placenta and amniotic fluid. 7,11,[14][15][16][17] HPV strains 6,11,16,18, and 31 have been shown to replicate in trophoblast cell lines, [18][19][20] where HPV infection decreased trophoblast number and trophoblast-endometrial cell adhesion in vitro. 19,20 We investigated for the presence of HPV in the placenta and carried out a histopathological and molecular cross-sectional study of 339 placentae from complicated and uncomplicated pregnancies.…”

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confidence: 99%

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A clinicopathological study of episomal papillomavirus infection of the human placenta and pregnancy complications

et al. 2015

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Viral infections are known to adversely affect pregnancy, but scant attention has been given to human papilloma virus (HPV) infection. We aimed to determine the molecular and histopathological features of placental HPV infection, in association with pregnancy complications including fetal growth restriction, pre-maturity, pre-eclampsia, and diabetes. Three hundred and thirty-nine placentae were selected based on the presence or absence of pregnancy complications. Five independent methods were used to identify HPV in the placenta, namely, immunohistochemistry for L1 viral capsid, in situ hybridization to high-risk HPV DNA, PCR, western blotting, and transmission electron microscopy. Pregnancy complications and uterine cervical smear screening results were correlated with placental HPV histopathology. In this study, which was deliberately biased towards complications, HPV was found in the decidua of 75% of placentae (253/339) and was statistically associated with histological acute chorioamnionitis (P o0.05). In 14% (35/253) of the HPV positive cases, HPV L1 immunoreactivity also occurred in the villous trophoblast where it was associated with a lymphohistiocytic villitis (HPV-LHV), and was exclusively of high-risk HPV type. HPV-LHV significantly associated with fetal growth restriction, preterm delivery, and pre-eclampsia (all P o0.05). All cases of pre-eclampsia (20/20) in our cohort had high-risk placental HPV. A further 55 cases (22%, 55/253) of HPV positive placentae had minimal villous trophoblast HPV L1 immunoreactivity, but a sclerosing pauci-immune villitis, statistically associated with diabetes (49.1%, 27/55, Po 0.05). For women with placental HPV, 33% (69/207) had an HPV-related positive smear result before pregnancy compared with (9.4% 8/85) of women with HPV-negative placentae (P = 0.0001). Our findings support further investigations to determine if vaccination of women and men will improve pregnancy outcomes. Modern Pathology (2015Pathology ( ) 28, 1369Pathology ( -1382 doi:10.1038/modpathol.2015 published online 21 August 2015 In the immune and hormonal modulated milieu of pregnancy, viruses are well known to infect the placenta, developing fetus, and neonate. The most common and important neoplastic driver of the lower uterine tract, human papillomavirus (HPV), 1 has been detected in the uterine cervix of 15-25% of pregnant women 2-6 and a cervical HPV infection during pregnancy has been associated with a higher incidence of spontaneous abortions, 7-9 premature rupture of the membranes, 10 spontaneous preterm labor, 11,12 pre-eclampsia, 13 and placental 'villitis' not otherwise specified. 12 HPV DNA has been detected in the placenta and amniotic fluid. 7,11,[14][15][16][17]11,16,18,and 31 have been shown to replicate in trophoblast cell lines, [18][19][20] where HPV infection decreased trophoblast number and trophoblast-endometrial cell adhesion in vitro. 19,20 We investigated for the presence of HPV in the placenta and carried out a histopathological and molecular cross-sectional study of 339 ...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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A clinicopathological study of episomal papillomavirus infection of the human placenta and pregnancy complications

et al. 2015

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“…In investigating the etiopathogenesis of sPTB, studies have focused on genetically determined molecular mechanisms in the inflammatory process (23,24), identifying that cytokine gene polymorphisms were related to sPTB (24). Placental apoptosis may also be involved: An imbalance between reactive oxygen species and antioxidants may result in excessive oxidative stress that triggers trophoblast apoptosis and initiates labour by upregulating expression of the JNK, MST3 and CASP3 genes, as depicted in Fig.…”

Section: Jnk/casp3 --------------------------------------------------mentioning

confidence: 99%

Induction of the apoptotic pathway by oxidative stress in spontaneous preterm birth: Single nucleotide polymorphisms, maternal lifestyle factors and health status

et al. 2018

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Abstract. The purpose of the present study was to search for associations between spontaneous preterm birth (sPTB), single nucleotide polymorphisms (SNPs) associated with the apoptotic pathway as triggered by oxidative stress, maternal lifestyle and health status. SNP genotyping [rs7560 for c-Jun N-terminal kinase (JNK), rs9517320 for mammalian STE20-like protein kinase 3 (MST3), rs1049216 for caspase 3 (CASP3)] in the placenta and maternal blood of 300 controls with at-term birth and 43 cases of sPTB was performed. No association was identified in genotype frequencies or combinations of foetal/maternal genotypes between single SNPs and sPTB. The risk of sPTB was significantly reduced by physical activity and significantly increased by current hypertensive diseases, premature rupture of membranes (PROM) or preterm PROM (P-PROM) and previous sPTB. The TT/GA genotype of JNK/CASP3 in maternal blood and maternal health status (current hypertensive diseases, current PROM/ P-PROM, previous sPTB) were independently associated with sPTB. The present findings suggested that, independently of other maternal factors, pregnant women carrying the TT/GA genotype of JNK/CASP3 were more susceptible to sPTB than women bearing the GT/GA (our reference) genotype; that the apoptotic pathway triggered by oxidative stress was involved; and that genetic and non-genetic factors contributed to sPTB. Knowledge of these aspects may aid to improve the management of pregnancies by indicating the lifestyle to be adopted on the basis of sPTB susceptibility.

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“…The most frequent causes of pregnancy loss in the first trimester are of genetic origin (4). Other important risk factors are maternal age, placental inflammation and infection (5,6); however, the etiology is often uncertain.…”

Section: Introductionmentioning

confidence: 99%

Detection of Herpes Simplex Virus Infection in Patients With Ongoing Miscarriage Using Serological Tests and Real-Time Polymerase Chain Reaction

Conde-Ferráez

Canché-Pech²,

Ayora-Talavera³

et al. 2016

Biotech Health Sci

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Background: Herpes simplex virus (HSV) is one of the most frequent viruses affecting females' sexual and reproductive health. Objectives: The current study aimed to determine the HSV serostatus and viral shedding in patients with ongoing miscarriage. Methods: Two hundred and eight females were included in the study; IgM antibodies against HSV1/2 were detected in serum samples; the real-time polymerase chain reaction (PCR) quantification of viral DNA was performed on cervicovaginal samples. Positive females were tested for IgG anti-HSV-2. Results: The results indicated 12.5% IgM-positive and 2.9% real-time PCR positive samples. None of the patients was positive for the both analyses, simultaneously. Among IgM-positives cases, 16.6% were also IgG-positive; whilst in PCR-positives samples, 20% were also IgG-positive. The presence of viral DNA without detectable IgM or IgG antibodies could indicate a recent infection or a reactivation with low copy numbers. Conclusions: IgM alone is not a marker for viral shedding in genital tract. Molecular testing in conjunction of IgG test should be evaluated as an option to determine HSV status, and applied for research on HSV genital infections records.

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Placental inflammation and viral infection are implicated in second trimester pregnancy loss

Cited by 129 publications

References 20 publications

A clinicopathological study of episomal papillomavirus infection of the human placenta and pregnancy complications

A clinicopathological study of episomal papillomavirus infection of the human placenta and pregnancy complications

Induction of the apoptotic pathway by oxidative stress in spontaneous preterm birth: Single nucleotide polymorphisms, maternal lifestyle factors and health status

Detection of Herpes Simplex Virus Infection in Patients With Ongoing Miscarriage Using Serological Tests and Real-Time Polymerase Chain Reaction

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