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Rebecca C. Bott, Ryann M. McFee, Debra T. Clopton, Candice F. Toombs, and Andrea S. Cupp. Biol Reprod 2006; 75:56–67. Published online ahead of print 3 May 2006; DOI 10.1095/biolreprod.105.047225
Unraveling VEGF signaling in gonad development. Key events in the complex process of testicular morphogenesis include migration of cells from the mesonephros into the developing gonad that include peritubular cells as well endothelial cells leading to male-specific neovascularization. However, neither the precise cell lineages nor the signaling pathways involved are well defined. In a paper on p. 56 of this issue, Bott et al. make significant steps toward elucidating a pathway for seminiferous cord formation and vascular development. They document the presence of transcripts and protein for both VEGFA and its receptor, KDR (previously known as VEGFR2), during critical days of cord formation. Furthermore, VEGFA signaling inhibitors block cord formation and reduce vascularization in embryonic testis cultures. Evidence that the signaling involves a phosphoinositide 3-kinase pathway emerged from the observation that a PIK3 inhibitor diminished both seminiferous cord formation and vascular density. This first evidence for the involvement of the angiogenic factor VEGFA in testis morphogenesis lays the foundation for further exciting work elucidating cellular signaling pathways and the role of the vasculature.
Large Offspring or Large Placenta Syndrome? Morphometric Analysis of Late Gestation Bovine Placentomes from Somatic Nuclear Transfer Pregnancies Complicated by Hydrallantois.
F. Constant, M. Guillomot, Y. Heyman, X. Vignon, P. Laigre, J.L. Servely, J.P. Renard, and P. Chavatte-Palmer. Biol Reprod 2006; 75:122–130. Published online ahead of print 29 March 2006; DOI 10.1095/biolreprod.106.051581
Large offspring or large placenta? On p. 122 of this issue, Constant and coworkers reported on a problem associated with offspring resulting from somatic cell nuclear transfer (NT). The title of their paper, "Large Offspring or Large Placenta Syndrome? Morphometric Analysis of Late Gestation Bovine Placentomes from Somatic Nuclear Transfer Pregnancies Complicated by Hydrallantois," indicates that their research focuses on one outcome of NT in cattle, namely Large Offspring Syndrome associated hydrallantois and placentomegaly in late gestation. Placentome structure of conceptuses derived from NT that exhibited hydrallantois (NTH) was examined for relationships to fetal and placental weights in the latter third of gestation. Results indicated that: 1) placental overgrowth preceded fetal overgrowth; 2) fetal/total placentome weight ratio was less in NTH versus control conceptuses after Day 220; and 3) stereological analyses revealed primary dergulation of growth of cotyledonary tissues. Thinning of the maternal epithelium within placentomes and increased surface area of trophoblast were considered secondary consequences of placental growth deregulation reflecting modifications in expression of placental factors. Various indicators of placental deficiency suggested that some fetal abnormalities in NTH calves, e.g., enlarged heart, enlarged umbilical cord, and abdominal ascites result from placental dysfunction. Consequently, the authors suggest that ‘Large Placenta Syndrome’ should replace ‘Large Offspring Syndrome’ to describe this syndrome which affects about 50 percent of conceptuses resulting from NT during late gestation. These findings will no doubt generate productive discussion among workers in this area of investigation.
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