Expression and localization of VEGF receptors in human fetal skeletal tissues.

During development the vertebrate skeleton is the product of deriving cells from distinct embryonic lineages. The craniofacial skeleton is formed by migrating cranial neural crest cells, whereas the axial and limb skeletons are derived from mesodermal cells. The Vascular Endothelial Growth Factors (VEGFs) / receptors (VEGFRs) system plays an important role in angiogenesis, as well as osteogenesis, during bone development, growth, and remodeling, attracting endothelial cells and osteoclasts and stimulating osteoblast differentiation. Recent evidence has shown that during development VEGFR-3 is also expressed in neural and glial precursors of forebrain and cerebellum, as well as in the eye. In this study, we found that VEGFR-1, VEGFR-2 and VEGFR-3 are expressed in human bone both in fetal and adult life. The gene expression levels were significantly higher in fetal samples especially in mandibles. In addition, higher levels of VEGFR-3 in orofacial district were confirmed by western blotting analysis. We also observed that in fetal mandibular samples VEGFRs colocalized in several osteoblasts, osteoclasts and osteoprogenitor cells. Furthermore, some cells coexpressed VEGFR-3 and ET-1, a marker of neural crest cells. The results demonstrated different expression of VEGFRs in human mandibular and femoral bones which could be correlated to their different structure, function and development during organogenesis. VEGFR-3 might represent a specific signal for ectomesenchymal lineage differentiation during early human development.

Incidence at birth and natural history of cryptorchidism: a study of 10,730 consecutive male infants.

Of the 10,730 neonates born in the period 1978-1997 and examined for cryptorchidism (C) at birth, 1387 were pre-term (gestational age <37 wk), and 9343 were full-term. At birth, a total of 737 neonates (6.9%) were cryptorchid, 487 had bilateral C and 250 unilateral C. The C rate of pre-terms was 10 times higher than that of the full-terms (30.1 and 3.4%, respectively). Comparing the two studied decades, a significant decrease of C rate was found in the second decade in full-term neonates. The rates of C at birth were significantly elevated for low birth weight, babies born from mothers with an age <20 or >35 yr, newborns from mothers with A Rh positive and B Rh positive blood group. Of the 737 cryptorchid newborns at birth, 613 (83%) were re-examined after 12 months from the expected date of delivery, and those born in the period 1988-1997 were also re-evaluated at 6 months of life. Late spontaneous descent occurred in 464 cases (75.7%), while 149 (24.3%) were still cryptorchid. The incidence of C at 12 months from the expected date of delivery, after survival curve calculation, in term and pre-term infants, was 1.53 and 7.31%, respectively, in the period 1978-1987, and 1.22 and 3.13% respectively, in the 2nd decade (1988-1997). In the groups also examined at 6 months of life, spontaneous descent occurred almost completely within the first 6 months of life in term infants, but not in pre-terms. No evidence of seasonal cyclicity was found. Medical and/or surgical treatment was generally started within 2-4 yr of age earlier in the second decade of the study. In conclusion, the main risk factor for C at birth and at 12 months of life seems to be pre-term birth and low birth weight. If this is associated itself to a higher risk of infertility too, it remains to be defined.

Adrenarche, pubertal development, age at menarche and final height of full-term, born small for gestational age (SGA) girls.

Children born small for gestational age (SGA) may present advanced bone maturation in childhood and reduced final height. The objectives of the study were to evaluate adrenarche, pubertal development, age at menarche and final height in full-term born-SGA girls. Twenty-four girls (12 born-SGA and 12 matched controls) were evaluated at 6-7.5 years of age for clinical signs of puberty and dehydroepiandrosterone sulfate (DHEAS) levels, as a marker of adrenarche. Thirty-eight girls (19 born-SGA and 19 matched controls) were evaluated at 17.5-18.5 years of age to assess final height, sexual maturation and age at menarche. SGA girls had a mean final height (160.1 cm vs 165.8 cm, p < 0.01) and mean weight (52.1 kg vs 56.5 kg, p < 0.05) significantly lower than controls. Controls had a mean final height significantly higher than their mean target height. Sexual maturation was at stage 5 of Tanner's staging in SGA girls and control subjects. SGA girls had a slightly anticipated puberty (9.9 vs 10.4 years for initial breast development) and a lower age at menarche (11.9 vs 12.3 years). At 6-7.5 years of age, SGA females and controls did not show any difference for clinical signs of puberty; however, DHEAS levels (0.75 + 0.18 microgram/ml vs 0.57 + 0.22 microgram/ml, p < 0.05) were significantly higher in SGA girls than in control subjects. We concluded that full-term born-SGA females have impaired final height and weight in adolescence but substantially normal sexual maturation and age at menarche. Increased DHEAS levels before puberty in born-SGA girls may predispose to increased bone maturation in childhood with a reduced final height. In our population a progressive increment in final stature is evident.