Inhibition of Early Luteal Angiogenesis by Gonadotropin-Releasing Hormone Antagonist Treatment in the Primate

Angiogenesis during luteal development is essential for normal lutein cell function, but the control of this process and the relationships between the steroidogenic and endothelial cells have still to be elucidated. The aim of this study was to: 1) quantify endothelial cell proliferation throughout the luteal phase of the marmoset ovulatory cycle; 2) determine the effect of gonadotropin withdrawal using GnRH antagonist treatment on the early luteal phase angiogenesis peak; and 3) describe the resultant morphological changes in the corpus luteum (CL). Ovaries were collected during the early, mid-, and late luteal phase, and changes in angiogenic activity were determined by quantification of bromodeoxyuridine incorporation. Animals were treated with a GnRH antagonist, on luteal days 1 and 2, and ovaries were collected on day 3. A proliferation index was obtained by counting the number of bromodeoxyuridine immunopositive cells in luteal sections. Cell proliferation was maximal in the early luteal phase and fell significantly in the mid- and late CL. GnRH antagonist treatment reduced the early luteal phase proliferation peak by 90%, suppressed plasma progesterone, and severely disrupted lutein cell morphology. These results demonstrate that the intense angiogenesis in the early primate CL is dependent on gonadotropin stimulation of lutein cells.