The long-term objective of this continuing research is to determine how different cell types within the primate corpus luteum contribute to luteal function, regulation and lifespan during the menstrual cycle. Experiments in this laboratory indicate that multiple subpopulations of nonhuman primate (macaque) luteal cells exist based on functional and regulatory differences in steroid production. Most recently, we reported results based on immunocytochemical localization of steroidogenic enzymes that are consistent with a two-cell model for steroid hormone production in the primate corpus luteum the paraluteal (theca-luteal) cells around the periphery and along the vascular tracts produce androgen substrate which is converted to estrogen by the true (granulosa-) luteal cells in the central parenchyma. However, little is known about the development and activities of the cell type that comprises the largest population in the corpus luteum - the endothelial cells forming the extensive microvasculature. Elegant research in other systems implicated two classes of factors, which act specifically on endothelial or peri-endothelial cells, as key payers in the development, maintenance and remodeling of the vasculature (1) the vascular endothelial growth factors (VEGF), and (2) the angiopoietins (Ang). Recent studies in our laboratory determined that the midcycle gonadotropin surge increases VEGF production more than 8-fold by granulosa cells in the preovulatory follicle. Moreover, when granulosa cells collected from maturing follicles are exposed to """"""""surge levels"""""""" of gonadotropin during 6 days of culture, VEGF production increases over 200-fold. Reverse transcription-polymerase chain reaction assays indicate that mRNAs encoding all three types of VEGF (-A, -B, and -C), two types of ANG (-1 and -2), plus their receptors, are present in macaque luteal tissue. These studies suggest that all the necessary components for endothelial-specific control of angiogenesis are present in the developing corpus luteum. Moreover, the midcycle gonadotropin surge may promote neovascularization of the luteinizing follicle by stimulating VEGF expression. Further studies will examine the production, regulation and action of the various types of VEGF and Ang in the periovulatory follicle and their role(s) in development of the corpus luteum of the menstrual cycle. This research may identify novel (i.e., local vascular) processes whose disruption could lead to specific types of infertility (e.g., anovulation, luteal phase defects) and suggest unique contraceptive approaches.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Primate Research Center Grants (P51)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Oregon Regional Primate Research Center
United States
Zip Code
Okoye, Afam A; Hansen, Scott G; Vaidya, Mukta et al. (2018) Early antiretroviral therapy limits SIV reservoir establishment to delay or prevent post-treatment viral rebound. Nat Med 24:1430-1440
Jensen, Jeffrey T; Hanna, Carol; Mishler, Emily et al. (2018) Effect of menstrual cycle phase and hormonal treatments on evaluation of tubal patency in baboons. J Med Primatol 47:40-45
Toro, C A; Aylwin, C F; Lomniczi, A (2018) Hypothalamic epigenetics driving female puberty. J Neuroendocrinol 30:e12589
Bulgarelli, Daiane L; Ting, Alison Y; Gordon, Brenda J et al. (2018) Development of macaque secondary follicles exposed to neutral red prior to 3-dimensional culture. J Assist Reprod Genet 35:71-79
Prola-Netto, Joao; Woods, Mark; Roberts, Victoria H J et al. (2018) Gadolinium Chelate Safety in Pregnancy: Barely Detectable Gadolinium Levels in the Juvenile Nonhuman Primate after in Utero Exposure. Radiology 286:122-128
Moccetti, Federico; Brown, Eran; Xie, Aris et al. (2018) Myocardial Infarction Produces Sustained Proinflammatory Endothelial Activation in Remote Arteries. J Am Coll Cardiol 72:1015-1026
Blue, Steven W; Winchell, Andrea J; Kaucher, Amy V et al. (2018) Simultaneous quantitation of multiple contraceptive hormones in human serum by LC-MS/MS. Contraception 97:363-369
Jeon, Sookyoung; Li, Qiyao; Rubakhin, Stanislav S et al. (2018) 13C-lutein is differentially distributed in tissues of an adult female rhesus macaque following a single oral administration: a pilot study. Nutr Res :
Slayden, Ov Daniel; Friason, Francis Kathryn E; Bond, Kise Rosen et al. (2018) Hormonal regulation of oviductal glycoprotein 1 (OVGP1; MUC9) in the rhesus macaque cervix. J Med Primatol 47:362-370
Dissen, G A; Adachi, K; Lomniczi, A et al. (2017) Engineering a gene silencing viral construct that targets the cat hypothalamus to induce permanent sterility: An update. Reprod Domest Anim 52 Suppl 2:354-358

Showing the most recent 10 out of 492 publications