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This study was designed to examine the contribution of plasma lipids to the pathophysiology of cyclic mastopathy, before and after consideration of diet and sex hormones.Thirty-four women with severe cyclic mastopathy (case patients) and 29 women without cyclic mastopathy (control subjects) recorded their breast symptoms daily during 1 menstrual cycle. During each menstrual phase (follicular, early luteal, late luteal, and menstrual) they prospectively completed 2 24-hour dietary diaries, provided blood for lipid and hormone assays, and underwent anthropometric measurements.Mean age was 34 years. Premenstrual breast swelling and tenderness were significantly more severe in case patients (P.0001). Cyclic change (late luteal vs follicular) of high-density lipoprotein cholesterol differed between case patients and control subjects, with case patients having a relative excess of high-density lipoprotein cholesterol in the premenstrual phase (P = .01). Dietary fat intake was greater throughout the cycle in case patients (37.5 vs 33.7% of calories, P = .02), and case patients reported increased appetite in the premenstrual phase (P = .01). In multivariate analyses the contributions of mean dietary fat intake and of cyclic change in high-density lipoprotein cholesterol were independently significant, with odds ratios for upper versus lower quintiles being slightly5.Women with cyclic mastopathy had a relative excess of high-density lipoprotein cholesterol during the symptomatic late luteal phase of the menstrual cycle and a higher fat intake throughout the cycle than did control subjects. These observations support the hypothesis that lipids (notably high-density lipoprotein cholesterol) and a high-fat diet play a role in the pathophysiologic characteristics of cyclic mastopathy.

The spatiotemporal distribution of two angiogenic growth factors, platelet-derived endothelial cell growth factor (PDECGF) and vascular endothelial growth factor (VEGF) were determined using immunohistochemistry on sections of human placentae from each trimester of pregnancy. In the first trimester PDECGF was detected in trophoblast and in a band in the centre of the villous core. During gestation staining spread throughout the stroma but began to weaken in trophoblast until, by term, it was found only in stroma and in some endothelial cells. VEGF was detected exclusively in cytotrophoblast during the first trimester and then in syncytiotrophoblast throughout the remainder of pregnancy. Western blot analysis revealed that PDECGF antisera bound to three bands approximately 27, 47 and 94 kDa. The lowest band was not detected in platelet lysate and may represent an alternatively processed form of this peptide in placenta. VEGF antisera bound strongly to bands approximately 36, 46, 54, 56 and 64 kDa. The intensity of most bands increased between the first and second trimesters, consistent with an increased level of angiogenesis as the placenta develops. The presence of both factors in trophoblast in early pregnancy may be indicative of the trophoblast playing an active role in influencing the development of the villous vascular network.

The histomorphometry of term placentae from women who exercised regularly throughout either the first half or all of pregnancy was compared to that of placentae from matched controls to determine if regular exercise during pregnancy produced histomorphometric evidence of altered development and transport capacity. Conventional stereological techniques were used to estimate placental volumetric composition, surface areas, and villous and vascular configurations in the three groups. Exercise confined to early pregnancy increased the parenchymal component of the placenta, total vascular volume and site-specific capillary volume and surface area. Exercise throughout pregnancy increased these and multiple other histomorphometric parameters associated with the rate of placental perfusion and transfer function. However, significant changes were confined to villi > 80 microns in diameter. The localization of both the timing of the stimulus and the anatomical sites affected indicates that regular, sustained exercise modifies placental development primarily in early and mid-pregnancy. We speculate that the lack of significant changes in the structure and configuration of the smaller villi indicates that other adaptive mechanisms, such as increased rates of placental blood flow, must be well developed by the latter portion of the mid-trimester and adequately maintain fetal oxygenation and substrate delivery throughout the third trimester.

OBJECTIVE Our purpose was to investigate the three-dimensional architecture of placental villi from normal and growth-restricted fetuses and relate findings to umbilical artery blood flow velocity waveforms. STUDY DESIGN Placentas from term (n = 15) and preterm (n = 5) appropriately grown and term (n = 9) and preterm (n = 7) growth-restricted fetuses (birth weight < 10th percentile) were examined to determine the number of arteries per stem villus and the three-dimensional configuration of the villous trees and their vessels. Umbilical blood flow before delivery was assessed by Doppler ultrasonography. The effects of age and growth restriction were determined by two-way analyses of variance. RESULTS Growth restriction was associated with reduced large vessel wall thickness (p < or = 0.05) but no reduction in the number of these vessels per stem villus. The volumes and surface areas of intermediate and terminal villi were reduced (p < or = 0.001), especially in preterm growth-restricted cases, where a marked reduction in diastolic blood flow velocity was observed in the umbilical artery. CONCLUSIONS Reduced villous development may contribute to abnormal umbilical artery blood flood flow, as assessed by Doppler ultrasonography, in some cases of intrauterine growth restriction.

The effect of hypoxic acidemia, hyperviscosity, and maternal hypertension on the umbilical arterial velocity waveform was studied in 23 chronically catheterized fetal sheep. Fetal hypoxic acidemia induced by lowering the maternal inspired oxygen concentration (n = 7) caused no change in the ratio of systolic/diastolic blood velocity even when fetal arterial pH was as low as 6.8. Fetal blood hyperviscosity (n = 7) induced by exchange transfusion with packed maternal blood cells increased placental vascular resistance by greater than or equal to 50% but had no significant effect on the systolic/diastolic ratio. Similarly, maternal hypertension induced by intravenous infusion of angiotensin II to the ewe (n = 9) did not affect the systolic/diastolic ratio despite a 50% increase in maternal arterial blood pressure. We conclude that umbilical arterial velocity waveform abnormalities observed in growth-restricted human fetuses are probably not a direct result of fetal hypoxemia or hyperviscosity or maternal hypertension.

Absent diastolic velocity and reversed diastolic velocity have been observed in the umbilical artery of growth-retarded human fetuses by means of Doppler ultrasonography. Because the physiologic mechanism is unknown, the purpose of this study was to determine whether such waveform changes could be induced in sheep fetuses by embolization of the resistance vessels of the placenta. Seven chronically catheterized sheep fetuses were instrumented with Doppler crystals mounted on one umbilical artery. The placenta was progressively embolized from the fetal side with plastic microspheres. In all cases the umbilical arterial waveform showed a progression from normal to zero diastolic velocity with embolization. In six of seven animals diastolic velocity eventually reversed in direction before fetal death. We conclude that occlusion of placental arteries and arterioles in fetal sheep recreates the waveform changes observed in severely growth-retarded human fetuses.

For clinical interpretation of Doppler waveforms, it is important to establish the extent to which fetal heart rate changes affect the umbilical artery velocity waveform. Umbilical artery waveforms were measured with continuous wave ultrasonography during spontaneous accelerations of the fetal heart rate in 20 uncomplicated, near-term pregnancies. On average, an acceleration of 20 beats/min of fetal heart rate within an individual was associated with a reduction in the systolic/diastolic velocity ratio of 0.25. There was, however, considerable variability in the response, and in six patients the systolic /diastolic ratio actually increased with heart rate. We conclude that fetal heart accelerations within the normal range cause only small and variable changes in the systolic/diastolic ratio.

It is common for women to undertake vigorous exercise in the late phase of pregnancy. This may have detrimental effects on the blood flow to the uterus and placenta or from the fetus to the placenta. Fifteen pregnant women with no obstetric or medical complications were subjected to a 5-minute exercise period. The maternal heart rate and blood pressure were elevated after exercise. The uteroplacental and umbilical circulations were assessed with Doppler ultrasonography. The ratio of the systolic/diastolic velocity in the uterine artery was elevated, which suggests that uteroplacental vascular resistance increased. The fetal heart rate was elevated after exercise, whereas the systolic/diastolic velocity ratio in the umbilical artery was unaltered. We conclude that moderate maternal exercise causes increased resistance to blood flow in the uterine circulation, whereas the umbilical circulation remains unaltered.