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Journal of Assisted Reproduction and Genetics

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01-02-2019 | Reproductive Physiology and Disease

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

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

Published in: Journal of Assisted Reproduction and Genetics | Issue 2/2019

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.

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Title: Treatment of female rhesus macaques with a somatostatin receptor antagonist that increases oocyte fertilization rates without affecting post-fertilization development outcomes
Authors: Alison Y. Ting
Melinda J. Murphy
Pablo Arriagada
Jean-Pierre Gotteland
Jon D. Hennebold
Publication date: 01-02-2019
Publisher: Springer US
Published in: Journal of Assisted Reproduction and Genetics / Issue 2/2019
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-018-1369-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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