Estrogen promotes germ cell and seminiferous tubule development in the baboon fetal testis.

The foundation for development of the male reproduction system occurs in utero, but relatively little is known about the regulation of primate fetal testis maturation. Our laboratories have shown that estrogen regulates key aspects of the physiology of pregnancy and fetal development. Therefore, in the present study, we characterized and quantified germ cells and Sertoli cells in the fetal baboon testis in late normal gestation (i.e., Day 165; term is 184 days) and in baboons administered the aromatase inhibitor letrozole throughout the second half of gestation to assess the impact of endogenous estrogen on fetal testis development. In untreated baboons, the seminiferous cords were comprised of undifferentiated (i.e., type A) spermatogonia classified by their morphology as dark (Ad) or pale (Ap), gonocytes (precursors of type A spermatogonia), unidentified cells (UI), and Sertoli cells. In letrozole-treated baboons, serum estradiol levels were decreased by 95%. The number per milligram of fetal testis (x10(4)) of Ad spermatogonia (0.42 +/- 0.11) was 45% lower (P = 0.03), and that of gonocytes (0.58 +/- 0.06) and UI (0.45 +/- 0.12) was twofold greater (P < 0.01 and P = 0.06, respectively), than in untreated baboons. Moreover, in the seminiferous cords of estrogen-deprived baboons, the basement membrane appeared fragmented, the germ cells and Sertoli cells appeared disorganized, and vacuoles were present. We conclude that endogenous estrogen promotes fetal testis development and that the changes in the germ cell population in the estrogen-deprived baboon fetus may impair spermatogenesis and fertility in adulthood.

Ontogeny and phagocytic function of baboon lung dendritic cells.

Dendritic cells (DCs) are the most potent antigen-presenting cells, but the ontogeny and functions of lung DCs are not known during prenatal period. Here, we isolated lung DC population from fetal (125-175 days of gestation age) and adult baboons. The cells were stained with fluorochrome-conjugated-HLA-DP, DQ, DR, CD1a, CD11c, CD14, CD40, CD80, CD86, CD209, CMKLR1, ILT7-specific antibodies, and staining was analyzed by flow cytometry. The phagocytic function was investigated by incubating the cells with fluorescent-labeled Escherichia coli bioparticles and analyzed by flow cytometry and fluorescence microscopy. The fetal baboon lung DCs expressed low levels of HLA-DP, DQ, DR, CD11c and CD86 as compared to adult baboon lung DCs and showed distinct DC morphology. The fetal lung DCs were also less capable of phagocytosing E. coli as compared to the adult lung DCs (P<0.05). In conclusion, the fetal lung DCs are not only phenotypically immature, but also less efficient in phagocytosing E. coli.

The timed-pregnant baboon animal model can be used for determining the role of soluble vascular endothelial growth factor receptors 1 and 2 during development.

BACKGROUND: During pregnancy, mechanisms that allow for regulation of continuous fetal and placental vasculogenesis with prevention of maternal neo-vascularization remain elusive. The vascular endothelial growth factor (VEGF) biological system has a key role during vasculogenesis. The aims of this study were to validate a bioassay for soluble vascular endothelial growth factor receptors 1 and 2 (sVEGFR-1 and sVEGFR-2) in baboon plasma and to determine the maternal and fetal plasma concentration of these receptors at the end of the baboon pregnancy. METHODS: Maternal peripheral blood samples were obtained from eight baboons (Papio anubis) prior to elective cesarean section and from the umbilical cord after the fetuses were delivered. Spike and recovery experiments at various concentrations in pooled baboon maternal plasma were used to validate a human quantitative sandwich immunoassay for sVEGFR-1 and -2. Concentrations of sVEGFR-1 and -2 were then determined in maternal and fetal plasma samples. RESULTS: No significant correlations were observed between sVEGFR-1 or -2 concentrations in maternal and fetal circulations. The concentration of sVEGFR-1 was at least 30 times greater and that of sVEGFR-2 approximately two times greater, in maternal than in cord plasma (both P < 0.01). CONCLUSION: These findings suggest that baboons can be used to study the regulation of vasculogenesis during pregnancy.