Treatment of female rhesus macaques with a somatostatin receptor antagonist that increases oocyte fertilization rates without affecting post-fertilization development outcomes

Alison Y. Ting, Melinda J. Murphy, Pablo Arriagada, Jean Pierre Gotteland, Jon D. Hennebold

Research output: Contribution to journalArticle

Abstract

Purpose: To determine the effects of PGL1001, a somatostatin receptor isoform-2 (SSTR-2) antagonist, on ovarian follicle development, oocyte fertilization, and subsequent embryo developmental potential in the rhesus macaque. Methods: Cycling female rhesus macaques (N = 8) received vehicle through one menstrual (control) cycle, followed by daily injections of PGL1001, a SSTR-2 antagonist, for three menstrual (treatment) cycles. Main endpoints include overall animal health and ovarian hormones (e.g., estradiol [E2], progesterone [P4], and anti-Müllerian hormone [AMH]), ovarian circumference, numbers of oocytes and their maturation status following controlled ovarian stimulation (COS), as well as oocyte fertilization and subsequent blastocyst rates that were assessed in control and PGL1001 treatment cycles. Circulating PGL1001 levels were assessed at baseline as well as 6, 60, and 90 days during treatment. Results: PGL1001 treatment did not impact overall animal health, menstrual cycle length, or circulating levels of ovarian hormones (E2, P4, and AMH) in comparison to vehicle treatment during natural cycles. PGL1001 treatment increased (p ˂ 0.05) ovarian circumference and the day 8 to day 1 ratio of AMH levels (p ˂ 0.05) during a COS protocol, as well as oocyte fertilization rates compared to the vehicle treatment interval. Blastocyst development rates were not significantly different between vehicle and PGL1001 treatment groups. Conclusion: Prolonged treatment with PGL1001 appears to be safe and does not affect rhesus macaque general health, menstrual cycle length, or ovarian hormone production. Interestingly, PGL1001 treatment increased the fertilization rate of rhesus macaque oocytes collected following ovarian stimulation.

Original languageEnglish (US)
Pages (from-to)229-239
Number of pages11
JournalJournal of Assisted Reproduction and Genetics
Volume36
Issue number2
DOIs
StatePublished - Feb 15 2019

Keywords

  • Embryo
  • Follicle development
  • Nonhuman primate
  • Oocyte
  • Somatostatin receptor antagonist

ASJC Scopus subject areas

  • Reproductive Medicine
  • Genetics
  • Obstetrics and Gynecology
  • Developmental Biology
  • Genetics(clinical)

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