The developmental origin and the specification of the adrenal cortex in humans and cynomolgus monkeys.

Development of the adrenal cortex, a vital endocrine organ, originates in the adrenogonadal primordium, a common progenitor for both the adrenocortical and gonadal lineages in rodents. In contrast, we find that in humans and cynomolgus monkeys, the adrenocortical lineage originates in a temporally and spatially distinct fashion from the gonadal lineage, arising earlier and more anteriorly within the coelomic epithelium. The adrenal primordium arises from adrenogenic coelomic epithelium via an epithelial-to-mesenchymal transition, which then progresses into the steroidogenic fetal zone via both direct and indirect routes. Notably, we find that adrenocortical and gonadal lineages exhibit distinct HOX codes, suggesting distinct anterior-posterior regionalization. Together, our assessment of the early divergence of these lineages provides a molecular framework for understanding human adrenal and gonadal disorders.

A study of oligosaccharide variants of alpha-fetoproteins produced by normal fetuses and fetuses with trisomy 21.

BACKGROUND: The mechanisms of the increase in the percentage of alpha-fetoproteins (AFPs) that strongly binds to Lens culinaris agglutinin (AFP-L3) in pregnancies with a trisomy 21 fetus have not been analyzed. To investigate the oligosaccharide variants of AFP produced by normal fetuses and fetuses with trisomy 21, the lectin reactivity of AFP was analyzed. METHODS: Fetal liver tissue, amniotic fluid, and maternal serum were obtained from five normal pregnancies and five pregnancies with a trisomy 21 fetus. The percentages of AFP reactive to lectins were determined by lectin-affinity electrophoresis coupled with antibody-affinity blotting. RESULTS: The percentages of AFP-L3 in the fetal liver and the maternal serum were 23.9 and 27.0%, respectively, in normal pregnancies, and 28.7 and 38.5%, respectively, in pregnancies with a trisomy 21 fetus. There was no statistically significant difference between the percentage in the fetal liver and the percentage in the maternal serum in normal pregnancies; however, a significant difference (P < 0.01) was found in pregnancies with a trisomy 21 fetus. In regard to the percentage of AFP-L3 in the fetal liver, there was no significant difference; however, a significant difference (P < 0.05) was found in the maternal serum between normal pregnancies and pregnancies with a trisomy 21 fetus. CONCLUSIONS: The transference of the AFP-L3 fraction might be relatively high in the placentas of women carrying a trisomy 21 fetus, and this could be the one of the reasons for the increase in the percentage of AFP-L3 in the maternal serum in pregnancies with a trisomy 21 fetus.

A study on the microheterogeneity of alpha-fetoproteins produced by yolk sac and germ cell tumors.

BACKGROUND: It is generally believed that the lower the grade of differentiation of glycoprotein-producing cells, the more often modification by bisecting N-acetylglucosamine (GlcNAc) or fucose (Fuc) at the sugar chain of the glycoprotein or increase in branching of side chains occurs. We examined the characteristics of the alpha-fetoprotein (AFP) sugar chain stored in amniotic and exocoelomic fluid during 5-9 weeks of gestation and analyzed serum-derived AFP of patients with germ cell tumors. METHODS: Total AFP concentrations in embryonic fluid at 5-9 weeks of gestation (n = 11) and serum of patients with germ cell tumors (n = 7) were measured using a radioimmunoassay (RIA) method. The percentages of AFPs reactive with Lens culinaris agglutinin (LCA), concanavalin A (Con A), erythroagglutinating phytohemagglutinin-E4 (E-PHA) and Ricinus communis agglutinin-120 (RCA 120) were obtained by lectin-affinity electrophoresis coupled with antibody-affinity blotting. RESULTS: It was revealed that at 5-9 weeks of gestation, AFP variants that had been modified by the Fuc residue, which bound to the GlcNAc residue at the reducing end of the sugar chain, and bisecting GlcNAc residues gradually decreased as pregnancy advanced; however, the presence of N-acetylneuraminic acid (Neu5Ac) at the nonreducing ends changed little. CONCLUSIONS: It appears very likely that the changes in the relative amounts of AFP variants in the embryonic fluid during early pregnancy were due to differentiation of the yolk sac. The grade of differentiation of yolk sac tumors was very similar to that of the normal yolk sac at around 6 weeks of gestation.

Prognostic significance of Bcl-2, p53 overexpression, and lymph node metastasis in surgically staged endometrial carcinoma.

OBJECTIVE: The purpose of this study was to clarify whether Bcl-2 and p53 have prognostic significance that is independent of lymph node metastasis and other conventional histopathologic factors in endometrial carcinoma. STUDY DESIGN: Immunohistochemistry for Bcl-2 and p53 expression was performed on the frozen sections of 102 cases that were treated with surgery, including pelvic and para-aortic lymphadenectomy. Cox regression analysis was used to determine the prognostic significance. RESULTS: By univariate analysis, both loss of Bcl-2 expression and p53 overexpression were related to patient survival. Lymph node metastasis, p53 overexpression, and nuclear grade were found to be independent prognostic factors (determined by multivariate analysis). The estimated 5-year survival rate of patients with stage III/IV disease without p53 overexpression was 75.7%; the estimated 5-year survival rate for patients with p53 overexpression was only 40.4%. The difference was highly significant (P =.0053). CONCLUSION: Lymph node metastasis, p53 overexpression, and nuclear grade are independent prognostic factors for endometrial carcinoma. Bcl-2 may have little importance in the progression of endometrial carcinoma and is a less potent prognostic factor than is p53. A new treatment strategy is necessary for advanced stage endometrial carcinoma with p53 overexpression.