Evidence that fetal death is associated with placental aging.

BACKGROUND: The risk of unexplained fetal death or stillbirth increases late in pregnancy, suggesting that placental aging is an etiological factor. Aging is associated with oxidative damage to DNA, RNA, and lipids. We hypothesized that placentas at >41 completed weeks of gestation (late-term) would show changes consistent with aging that would also be present in placentas associated with stillbirths. OBJECTIVE: We sought to determine whether placentas from late-term pregnancies and unexplained stillbirth show oxidative damage and other biochemical signs of aging. We also aimed to develop an in vitro term placental explant culture model to test the aging pathways. STUDY DESIGN: We collected placentas from women at 37-39 weeks' gestation (early-term and term), late-term, and with unexplained stillbirth. We used immunohistochemistry to compare the 3 groups for: DNA/RNA oxidation (8-hydroxy-deoxyguanosine), lysosomal distribution (lysosome-associated membrane protein 2), lipid oxidation (4-hydroxynonenal), and autophagosome size (microtubule-associated proteins 1A/1B light chain 3B, LC3B). The expression of aldehyde oxidase 1 was measured by real-time polymerase chain reaction. Using a placental explant culture model, we tested the hypothesis that aldehyde oxidase 1 mediates oxidative damage to lipids in the placenta. RESULTS: Placentas from late-term pregnancies show increased aldehyde oxidase 1 expression, oxidation of DNA/RNA and lipid, perinuclear location of lysosomes, and larger autophagosomes compared to placentas from women delivered at 37-39 weeks. Stillbirth-associated placentas showed similar changes in oxidation of DNA/RNA and lipid, lysosomal location, and autophagosome size to placentas from late-term. Placental explants from term deliveries cultured in serum-free medium also showed evidence of oxidation of lipid, perinuclear lysosomes, and larger autophagosomes, changes that were blocked by the G-protein-coupled estrogen receptor 1 agonist G1, while the oxidation of lipid was blocked by the aldehyde oxidase 1 inhibitor raloxifene. CONCLUSION: Our data are consistent with a role for aldehyde oxidase 1 and G-protein-coupled estrogen receptor 1 in mediating aging of the placenta that may contribute to stillbirth. The placenta is a tractable model of aging in human tissue.

Enlargement of the levator hiatus in female pelvic organ prolapse: cause or effect?

AIM: This study was undertaken to investigate whether female pelvic organ prolapse repair changes levator hiatal biometry. METHODS: Retrospective analysis of clinical and translabial ultrasound volume data of women who underwent prolapse surgery at a tertiary urogynaecological unit between March 2005 and April 2009. Data sets of 81 women were analysed who had undergone an interview, clinical assessment using POP-Q staging and 3D translabial ultrasound before and after prolapse surgery. Imaging data were obtained preoperatively and 3-12 months postoperatively to determine potential changes in levator hiatal dimensions. Type of surgery, mesh use, symptoms of recurrent prolapse, age, significant recurrent prolapse and length of follow-up were tested in linear regression as potential confounders. RESULTS: The mean preoperative hiatal area on Valsalva was 31.9 cm(2) (range 13.5-58.1 cm(2), SD 10.0 cm(2)). Mean postoperative hiatal area on Valsalva was 28.9 cm(2) (range 13.9-47.4 cm(2); SD 7.3 cm(2)), which implies a significant reduction of 9% (P = 0.001). None of the tested potential confounders were found to be significantly associated with a perioperative change in hiatal area on Valsalva on linear regression analysis. CONCLUSIONS: Surgery for female pelvic organ prolapse is associated with a small but significant reduction in hiatal area, but abnormal hiatal distensibility persists in most cases. This suggests that excessive hiatal distensibility is more likely the cause rather than the effect of prolapse.