Vertical transmission of Human papillomavirus: experience from a center of southern Italy.

BACKGROUND: Human papillomavirus (HPV) represents a group of DNA viruses, sexually transmitted, and widely accepted as a cause of invasive squamous cell carcinomas. The virus prevalence is critical worldwide. However, the possibility of perinatal transmission during pregnancy is not well understood as well as the risks for the newborn. METHODS: Our study analyzed pregnant women referred to the obstetric outpatient room of the Department of Gynecology and Obstetrics of Sant'Anna and San Sebastiano University Hospital in Caserta, Italy. Cervicovaginal samples were achieved from patients during the first trimester and tested for HPV. The specimen was repeated during the third trimester for HPV-positive patients. After the birth, we took a placenta sample and an eye, pharyngeal, mouth, and genital samples in children from HPV positive mothers, at 36-48 hours after birth and three and six months. RESULTS: We found out a high prevalence of HPV infections in the recruited patients: 71 participants were positive at the HPV test in the first trimester (45%), and 17 (14%) showed a positivity in the placental samples. However, there was a low prevalence of viral infection in newborns, and six newborns were positive for HPV at birth (9%). CONCLUSIONS: HPV vertical transmission represents a critical obstetric topic, and the transplacental passage of the virus represents a possible cause. However, further studies are necessary to deepen the pathological mechanism and assess the risks for the newborn.

The pattern of expression of Notch protein members in normal and pathological endometrium.

The objective of this study was to investigate the pattern of expression and the localization of Notch-1, Notch-4 and Jagged-1 in physiological and pathological human endometrium and to evaluate the expression levels of two major regulators of the G1 checkpoint, namely cyclin D1 and p21. Sixty samples of physiological endometrium and 60 samples of pathological endometrium were used for the study. Evaluation of the expression level and the distribution of Notch pathway members and cell-cycle proteins was performed by immunohistochemistry. In the physiological endometrium we observed an increase of Notch-1 and Jagged-1 from proliferative to secretory phase and an opposite trend for Notch-4. In menopause, the level of expression of all three members of the Notch pathway decreased. We also observed a cyclin D1 increase from proliferative to secretory phase. By contrast, p21 showed a slight increase from proliferative to secretory phase. In the pathological endometrium, we observed an increase of Notch-1 expression from polyps to carcinoma and decrease for Notch-4 and Jagged-1. Moreover, we observed a higher expression of cyclin D1 in all the endometrial pathologies. By contrast, the expression level of p21 slightly increased from polyps to carcinoma. We concluded that in human endometrium Notch-4 seems to be more involved in controlling proliferation, whereas Notch-1 seems to be more involved in differentiation programming. Deregulation of these functions may induce the onset of several endometrial pathologies from polyps to cancer.

Distribution of Notch protein members in normal and preeclampsia-complicated placentas.

Notch proteins are a transmembrane receptor family that is structurally and functionally conserved from worms to humans. The mammalian family of Notch proteins consists of several genes encoding Notch receptors and related Notch ligands. Notch signaling is involved in different aspects of the cell-fate decision tree: differentiation, proliferation, and apoptosis. These three processes are finely regulated in human placenta in order to allow a successful pregnancy and correct fetal growth. Notch and its ligands also participate in vascular remodeling and stabilization. Vasculogenesis and blood regulation are of importance in the human placenta for normal fetal development and growth; any disorder of these systems leads to preeclampsia. Drawing on this background, we have investigated the expression of Notch-1, Notch-4, and Jagged-1, together with two members related to the Notch pathway in angiogenesis: VEGF and p21. Normal and preeclamptic human placentas have been evaluated by immunohistochemistry. In preeclamptic samples, a down-regulation of Notch pathway members occurs with a weak/moderate expression of the Notch protein members in all components of placenta compared with physiological placentas that, at term, exhibit the strong expression of Jagged-1 and a moderate expression of both Notch-1 and Notch-4 in all compartments of the placental villi. Moreover, preeclamptic samples also reveal a down-regulation of VEGF expression, together with a moderate nuclear expression of p21(Cip1) in the syncytiotrophoblast, cytotrophoblast, and endothelial cells. This down-regulation of VEGF in preeclamptic placentas, in turn, probably decreases Notch protein expression in placental compartments and in endothelial cells and could offer an ethiopathogenetic explanation for the onset of this pathology.

Mid-trimester fetal-placental velocimetry response to nifedipine may predict early the onset of pre-eclampsia.

The effect of nifedipine on fetal-placental blood flow at 22-24 weeks in patients with pregnancy-induced hypertension (PIH) was evaluated. Twenty patients with PIH were submitted to the Doppler evaluation of fetal-placental perfusion at 22-24 weeks. The systo-diastolic (SID) ratio and the pulsatility index (PI) of uterine, umbilical and middle cerebral arteries and systemic blood pressure were recorded before and 7 days after nifedipine administration (10 mg/ per os 3 times/day until delivery). Statistical analysis was performed with paired and unpaired t-test and the two-tailed Fisher exact test. Nifedipine significantly (p < 0.05) decreased the mean systolic pressure in all patients (from 146 to 135 mmHg): 8 patients developed pre-eclampsia (PE) complicated by fetal growth restriction (FGR) (PE group), whilst the remaining were only affected by PIH (PIH group). The gestational age at delivery, neonatal birthweight and 1- and 5-min Apgar scores were significantly (p < 0.001) lower in PE than in PIH women. Nifedipine treatment significantly changed the PI and S/D ratio (mean +/- SEM) of the uterine (PI from 0.66 +/- 0.01 to 0.51 + 0.01; SID ratio: from 2.00 +/- 0.09 to 1.79 + 0.05) and umbilical (PI: from 1.55 +/- 0.04 to 1.40 +/- 0.02; S/D ratio: from 2.45 +/- 0.09 to 2.31+/- 0.09) arteries and the middle cerebral PI (from 1.45 +/- 0.03 to 1.61 +/- 0.01) artery only in PIH, but not in PE patients. Fetal-placental blood flow changes after nifedipine may early identify patients at risk of PE.

The serine protease HtrA1 is upregulated in the human placenta during pregnancy.

The placenta has a dynamic and continuous capacity for self-renewal. The molecular mechanisms responsible for controlling trophoblast proliferation are still unclear. It is generally accepted that the simultaneous activity of proteins involved in cell proliferation, apoptosis, and extracellular matrix degradation plays an important role in correct placental development. We investigated in depth the expression of the serine protease HtrA1 during pregnancy in human placenta by in situ hybridization and immunohistochemistry, we demonstrated that HtrA1 displayed a low level of expression in the first trimester of gestation and a strong increase of HtrA1 expression in the third trimester. Finally, by electron microscopy, we demonstrated that HtrA1 was localized either in the cytoplasm of placental cells, especially close to microvilli that characterized the plasma membrane of syncytiotrophoblast cells, or in the extracytoplasmic space of the stroma of placental villi, particularly in the spaces between collagen fibers and on collagen fibers themselves. The expression pattern of HtrA1 in human placentas strongly suggests a role for this protein in placental development and function. Moreover, on the basis of its subcellular distribution it can be postulated that HtrA1 acts on different targets, such as intracellular growth factors or extracellular matrix proteins, to favor the correct formation/function of the placenta.