Harvey Kliman MD, PhD Yale University Obstetrics & Gynecology School of Medicine 312 FMB Reproductive and Placental Research Unit, Dept Ob/Gyn Yale University New Haven, Connecticut United States 06520-8063
Juliette McSweet Yale University Ob/Gyn 312 FMB Yale University School of Medicine 333 Cedar Street New Haven, CT USA 06520-8063
Trang La Yale University Ob/Gyn 312 FMB Yale University School of Medicine 333 Cedar Street New Haven, CT USA 06520-8063
OBJECTIVE: To identify the cellular source of corticotropin releasing hormone (CRH) in the human placenta.
STUDY DESIGN: Human late third trimester placentas were immunohistochemically stained for CRH (clone 4H9, Biogenesis). Human hypothalamus served as the positive control tissue while normal mouse ascites (NMA) served as the negative control antibody.
RESULTS: The anti-CRH antibody stained the cell bodies of scattered neuronal elements within the hypothalamus while the NMA resulted in no immunostaining. Anti-CRH staining of the placentas revealed specific staining of syncytial knots of the villous syncytiotrophoblast layer (see figure). Little staining was noted in the flat, non-knotted portions of the syncytiotrophoblast layer.
CONCLUSION: Placental CRH is believed to promote fetal maturation by enhancing glucocorticoid production by the fetal adrenal gland. Placental CRH expression is further stimulated by the antagonistic binding of progesterone and cortisol to glucocorticoid receptors in the placenta. The result is a positive feedback loop between placental CRH and cortisol, which are consistent with the increases in fetal cortisol level, CRH level, DHEA level, and fetal adrenal growth observed at the end of gestation. This positive feedback loop is suggested to be the regulator of the placental clock that drives the increases in the mediators of labor. These stimulatory actions are coupled with the glucocorticoid effects on fetal organ maturation with the timing of parturition. We hypothesize that the adaptive placental response to the intrauterine stresses of term pregnancy or preterm uteroplacental insufficiency is the formation of syncytial knots. Therefore, the formation of syncytial knots is the critical event that promotes fetal maturation and parturition.
CRH only stains the syncytial knots of the chorionic villi. Third trimester placenta chorionic villi stained with anti-CRH antibody. A) Prominent CRH positive syncytial knot (red arrow) containing many nuclei is seen in the center of the field. The syncytium near this knot contains some CRH (orange arrowheads), possibly due to diffusion within the contiguous syncytial trophoblast cytoplasm. Syncytial trophoblasts not adjacent to the positive knot are negative (pink arrows). B, C) CRH positive syncytial knots (red arrows) with surrounding negative syncytium (pink arrows). D) Higher power view of large polyp-like syncytial knot that is strongly CRH positive (red arrows). The nearby syncytium is only lightly stained or negative for CRH (pink arrows).
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Last modified 6/16/01