Changes in circulating levels and ratios of angiopoietins during pregnancy but not during the menstrual cycle and controlled ovarian stimulation

ObjectiveTo determine whether angiopoietin (ANGPT)-1 and -2 are detectable in the circulation of nonhuman primates and women and whether these levels fluctuate in association with ovarian activity.DesignProspective.SettingNational Primate Research Center, medical center, and infertility clinic.Patient(s)Adult female rhesus monkeys; 15 women donating oocytes for infertility treatment.Intervention(s)Controlled ovarian stimulation with gonadotropins, removal of the corpus luteum and ovaries, oocyte retrieval, and ET.Main Outcome Measure(s)Circulating levels of ANGPT-1 and ANGPT-2.Result(s)Serum ANGPT-1 and ANGPT-2 levels were detectable and invariant in maintaining an ANGPT-1 to -2 ratio >1 in [1] macaques over the course of the natural menstrual cycle, during a controlled ovulation protocol, and after removal of the corpus luteum or ovaries and [2] women undergoing controlled ovarian simulation. In contrast, the ANGPT-1 to -2 ratio was markedly decreased (<<1) at mid-to-late gestation in macaques and in the follicular fluid of women undergoing controlled ovarian simulation because of increased levels of ANGPT-2.Conclusion(s)The ovary and its dominant structures are not major contributors to circulating levels of ANGPT-1 or ANGPT-2. The physiologic importance of the rising levels of ANGPT-2 after the luteal-placental shift in pregnancy is unknown.