Skip to main content
Erschienen in: Journal of Assisted Reproduction and Genetics 2/2019

15.11.2018 | 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

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

Erschienen in: Journal of Assisted Reproduction and Genetics | Ausgabe 2/2019

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr Rev. 1996;17(2):121–55.PubMedCrossRef Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr Rev. 1996;17(2):121–55.PubMedCrossRef
2.
Zurück zum Zitat Macklon NS, Fauser BC. Aspects of ovarian follicle development throughout life. Horm Res. 1999;52(4):161–70.PubMed Macklon NS, Fauser BC. Aspects of ovarian follicle development throughout life. Horm Res. 1999;52(4):161–70.PubMed
3.
Zurück zum Zitat Fortune JE, Cushman RA, Wahl CM, Kito S. The primordial to primary follicle transition. Mol Cell Endocrinol. 2000;163(1–2):53–60.PubMedCrossRef Fortune JE, Cushman RA, Wahl CM, Kito S. The primordial to primary follicle transition. Mol Cell Endocrinol. 2000;163(1–2):53–60.PubMedCrossRef
4.
Zurück zum Zitat Fauser BC, Van Heusden AM. Manipulation of human ovarian function: physiological concepts and clinical consequences. Endocr Rev. 1997;18(1):71–106.PubMed Fauser BC, Van Heusden AM. Manipulation of human ovarian function: physiological concepts and clinical consequences. Endocr Rev. 1997;18(1):71–106.PubMed
5.
Zurück zum Zitat Murray PG, Higham CE, Clayton PE. 60 years of neuroendocrinology: the hypothalamo-GH axis: the past 60 years. J Endocrinol. 2015;226(2):T123–40.PubMedCrossRef Murray PG, Higham CE, Clayton PE. 60 years of neuroendocrinology: the hypothalamo-GH axis: the past 60 years. J Endocrinol. 2015;226(2):T123–40.PubMedCrossRef
6.
Zurück zum Zitat Hejna M, Schmidinger M, Raderer M. The clinical role of somatostatin analogues as antineoplastic agents: much ado about nothing? Ann Oncol. 2002;13(5):653–68.PubMedCrossRef Hejna M, Schmidinger M, Raderer M. The clinical role of somatostatin analogues as antineoplastic agents: much ado about nothing? Ann Oncol. 2002;13(5):653–68.PubMedCrossRef
7.
Zurück zum Zitat Narayanan S, Kunz PL. Role of somatostatin analogues in the treatment of neuroendocrine tumors. J Natl Compr Cancer Netw. 2015;13(1):109–17.CrossRef Narayanan S, Kunz PL. Role of somatostatin analogues in the treatment of neuroendocrine tumors. J Natl Compr Cancer Netw. 2015;13(1):109–17.CrossRef
8.
Zurück zum Zitat Rai U, Thrimawithana TR, Valery C, Young SA. Therapeutic uses of somatostatin and its analogues: current view and potential applications. Pharmacol Ther. 2015;152:98–110.PubMedCrossRef Rai U, Thrimawithana TR, Valery C, Young SA. Therapeutic uses of somatostatin and its analogues: current view and potential applications. Pharmacol Ther. 2015;152:98–110.PubMedCrossRef
9.
Zurück zum Zitat Gevers TJ, Drenth JP. Somatostatin analogues for treatment of polycystic liver disease. Curr Opin Gastroenterol. 2011;27(3):294–300.PubMedCrossRef Gevers TJ, Drenth JP. Somatostatin analogues for treatment of polycystic liver disease. Curr Opin Gastroenterol. 2011;27(3):294–300.PubMedCrossRef
10.
Zurück zum Zitat Gambineri A, Patton L, De Iasio R, Cantelli B, Cognini GE, Filicori M, et al. Efficacy of octreotide-LAR in dieting women with abdominal obesity and polycystic ovary syndrome. J Clin Endocrinol Metab. 2005;90(7):3854–62.PubMedCrossRef Gambineri A, Patton L, De Iasio R, Cantelli B, Cognini GE, Filicori M, et al. Efficacy of octreotide-LAR in dieting women with abdominal obesity and polycystic ovary syndrome. J Clin Endocrinol Metab. 2005;90(7):3854–62.PubMedCrossRef
11.
Zurück zum Zitat Gahete MD, Cordoba-Chacon J, Duran-Prado M, Malagon MM, Martinez-Fuentes AJ, Gracia-Navarro F, et al. Somatostatin and its receptors from fish to mammals. Ann N Y Acad Sci. 2010;1200:43–52.PubMedCrossRef Gahete MD, Cordoba-Chacon J, Duran-Prado M, Malagon MM, Martinez-Fuentes AJ, Gracia-Navarro F, et al. Somatostatin and its receptors from fish to mammals. Ann N Y Acad Sci. 2010;1200:43–52.PubMedCrossRef
12.
Zurück zum Zitat Unger N, Ueberberg B, Schulz S, Saeger W, Mann K, Petersenn S. Differential expression of somatostatin receptor subtype 1-5 proteins in numerous human normal tissues. Exp Clin Endocrinol Diabetes. 2012;120(8):482–9.PubMedCrossRef Unger N, Ueberberg B, Schulz S, Saeger W, Mann K, Petersenn S. Differential expression of somatostatin receptor subtype 1-5 proteins in numerous human normal tissues. Exp Clin Endocrinol Diabetes. 2012;120(8):482–9.PubMedCrossRef
13.
Zurück zum Zitat Riaz H, Dong P, Shahzad M, Yang L. Constitutive and follicle-stimulating hormone-induced action of somatostatin receptor-2 on regulation of apoptosis and steroidogenesis in bovine granulosa cells. J Steroid Biochem Mol Biol. 2014;141:150–9.PubMedCrossRef Riaz H, Dong P, Shahzad M, Yang L. Constitutive and follicle-stimulating hormone-induced action of somatostatin receptor-2 on regulation of apoptosis and steroidogenesis in bovine granulosa cells. J Steroid Biochem Mol Biol. 2014;141:150–9.PubMedCrossRef
14.
Zurück zum Zitat Gougeon A, Delangle A, Arouche N, Stridsberg M, Gotteland JP, Loumaye E. Kit ligand and the somatostatin receptor antagonist, BIM-23627, stimulate in vitro resting follicle growth in the neonatal mouse ovary. Endocrinology. 2010;151(3):1299–309.PubMedCrossRef Gougeon A, Delangle A, Arouche N, Stridsberg M, Gotteland JP, Loumaye E. Kit ligand and the somatostatin receptor antagonist, BIM-23627, stimulate in vitro resting follicle growth in the neonatal mouse ovary. Endocrinology. 2010;151(3):1299–309.PubMedCrossRef
15.
Zurück zum Zitat Nakamura E, Otsuka F, Inagaki K, Tsukamoto N, Ogura-Ochi K, Miyoshi T, et al. Involvement of bone morphogenetic protein activity in somatostatin actions on ovarian steroidogenesis. J Steroid Biochem Mol Biol. 2013;134:67–74.PubMedCrossRef Nakamura E, Otsuka F, Inagaki K, Tsukamoto N, Ogura-Ochi K, Miyoshi T, et al. Involvement of bone morphogenetic protein activity in somatostatin actions on ovarian steroidogenesis. J Steroid Biochem Mol Biol. 2013;134:67–74.PubMedCrossRef
16.
Zurück zum Zitat Nestorovic NM, Manojlovic-Stojanoski MN, Trifunovic SL, Ristic NM, Filipovic BR, Sosic-Jurjevic BT, et al. Long-term effects of somatostatin 14 on the pituitary-ovarian axis in rats. Gen Physiol Biophys. 2014;33(2):157–68.PubMedCrossRef Nestorovic NM, Manojlovic-Stojanoski MN, Trifunovic SL, Ristic NM, Filipovic BR, Sosic-Jurjevic BT, et al. Long-term effects of somatostatin 14 on the pituitary-ovarian axis in rats. Gen Physiol Biophys. 2014;33(2):157–68.PubMedCrossRef
17.
Zurück zum Zitat Andreani CL, Lazzarin N, Pierro E, Lanzone A, Mancuso S. Somatostatin action on rat ovarian steroidogenesis. Hum Reprod. 1995;10(8):1968–73.PubMedCrossRef Andreani CL, Lazzarin N, Pierro E, Lanzone A, Mancuso S. Somatostatin action on rat ovarian steroidogenesis. Hum Reprod. 1995;10(8):1968–73.PubMedCrossRef
18.
Zurück zum Zitat Moaeen-ud-Din M, Malik N, Yang LG. Somatostatin can alter fertility genes expression, oocytes maturation, and embryo development in cattle. Anim Biotechnol. 2009;20(3):144–50.PubMedCrossRef Moaeen-ud-Din M, Malik N, Yang LG. Somatostatin can alter fertility genes expression, oocytes maturation, and embryo development in cattle. Anim Biotechnol. 2009;20(3):144–50.PubMedCrossRef
19.
Zurück zum Zitat Nestorovic N, Lovren M, Sekulic M, Filipovic B, Milosevic V. Effects of multiple somatostatin treatment on rat gonadotrophic cells and ovaries. Histochem J. 2001;33(11–12):695–702.PubMedCrossRef Nestorovic N, Lovren M, Sekulic M, Filipovic B, Milosevic V. Effects of multiple somatostatin treatment on rat gonadotrophic cells and ovaries. Histochem J. 2001;33(11–12):695–702.PubMedCrossRef
20.
21.
Zurück zum Zitat Wolf DP, Vandevoort CA, Meyer-Haas GR, Zelinski-Wooten MB, Hess DL, Baughman WL, et al. In vitro fertilization and embryo transfer in the rhesus monkey. Biol Reprod. 1989;41(2):335–46.PubMedCrossRef Wolf DP, Vandevoort CA, Meyer-Haas GR, Zelinski-Wooten MB, Hess DL, Baughman WL, et al. In vitro fertilization and embryo transfer in the rhesus monkey. Biol Reprod. 1989;41(2):335–46.PubMedCrossRef
22.
Zurück zum Zitat Macklon NS, Stouffer RL, Giudice LC, Fauser BC. The science behind 25 years of ovarian stimulation for in vitro fertilization. Endocr Rev. 2006;27(2):170–207.PubMedCrossRef Macklon NS, Stouffer RL, Giudice LC, Fauser BC. The science behind 25 years of ovarian stimulation for in vitro fertilization. Endocr Rev. 2006;27(2):170–207.PubMedCrossRef
23.
Zurück zum Zitat Wolf DP, Thomson JA, Zelinski-Wooten MB, Stouffer RL. In vitro fertilization-embryo transfer in nonhuman primates: the technique and its applications. Mol Reprod Dev. 1990;27(3):261–80.PubMedCrossRef Wolf DP, Thomson JA, Zelinski-Wooten MB, Stouffer RL. In vitro fertilization-embryo transfer in nonhuman primates: the technique and its applications. Mol Reprod Dev. 1990;27(3):261–80.PubMedCrossRef
24.
Zurück zum Zitat Hanna CB, Yao S, Ramsey CM, Hennebold JD, Zelinski MB, Jensen JT. Phosphodiesterase 3 (PDE3) inhibition with cilostazol does not block in vivo oocyte maturation in rhesus macaques (Macaca mulatta). Contraception. 2015;91(5):418–22.PubMedPubMedCentralCrossRef Hanna CB, Yao S, Ramsey CM, Hennebold JD, Zelinski MB, Jensen JT. Phosphodiesterase 3 (PDE3) inhibition with cilostazol does not block in vivo oocyte maturation in rhesus macaques (Macaca mulatta). Contraception. 2015;91(5):418–22.PubMedPubMedCentralCrossRef
25.
Zurück zum Zitat Bishop CV, Sparman ML, Stanley JE, Bahar A, Zelinski MB, Stouffer RL. Evaluation of antral follicle growth in the macaque ovary during the menstrual cycle and controlled ovarian stimulation by high-resolution ultrasonography. Am J Primatol. 2009;71(5):384–92.PubMedPubMedCentralCrossRef Bishop CV, Sparman ML, Stanley JE, Bahar A, Zelinski MB, Stouffer RL. Evaluation of antral follicle growth in the macaque ovary during the menstrual cycle and controlled ovarian stimulation by high-resolution ultrasonography. Am J Primatol. 2009;71(5):384–92.PubMedPubMedCentralCrossRef
26.
Zurück zum Zitat Young KA, Hennebold JD, Stouffer RL. Dynamic expression of mRNAs and proteins for matrix metalloproteinases and their tissue inhibitors in the primate corpus luteum during the menstrual cycle. Mol Hum Reprod. 2002;8(9):833–40.PubMedCrossRef Young KA, Hennebold JD, Stouffer RL. Dynamic expression of mRNAs and proteins for matrix metalloproteinases and their tissue inhibitors in the primate corpus luteum during the menstrual cycle. Mol Hum Reprod. 2002;8(9):833–40.PubMedCrossRef
27.
Zurück zum Zitat Xu J, Bernuci MP, Lawson MS, Yeoman RR, Fisher TE, Zelinski-Wooten MB, et al. Survival, growth, and maturation of secondary follicles from prepubertal, young and older adult, rhesus monkeys during encapsulated three-dimensional (3D) culture: effects of gonadotropins and insulin. Reproduction. 2010. Xu J, Bernuci MP, Lawson MS, Yeoman RR, Fisher TE, Zelinski-Wooten MB, et al. Survival, growth, and maturation of secondary follicles from prepubertal, young and older adult, rhesus monkeys during encapsulated three-dimensional (3D) culture: effects of gonadotropins and insulin. Reproduction. 2010.
28.
Zurück zum Zitat Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA, et al. Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod. 2004;10(2):77–83.PubMedCrossRef Weenen C, Laven JS, Von Bergh AR, Cranfield M, Groome NP, Visser JA, et al. Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod. 2004;10(2):77–83.PubMedCrossRef
29.
Zurück zum Zitat Thomas FH, Telfer EE, Fraser HM. Expression of anti-Mullerian hormone protein during early follicular development in the primate ovary in vivo is influenced by suppression of gonadotropin secretion and inhibition of vascular endothelial growth factor. Endocrinology. 2007;148(5):2273–81.PubMedCrossRef Thomas FH, Telfer EE, Fraser HM. Expression of anti-Mullerian hormone protein during early follicular development in the primate ovary in vivo is influenced by suppression of gonadotropin secretion and inhibition of vascular endothelial growth factor. Endocrinology. 2007;148(5):2273–81.PubMedCrossRef
30.
Zurück zum Zitat Mimuro T, Smith H, Iwashita M, Illingworth PJ. The somatostatin analogue, octreotide, modifies both steroidogenesis and IGFBP-1 secretion in human luteinizing granulosa cells. Hum Reprod. 1998;13(1):150–3.PubMedCrossRef Mimuro T, Smith H, Iwashita M, Illingworth PJ. The somatostatin analogue, octreotide, modifies both steroidogenesis and IGFBP-1 secretion in human luteinizing granulosa cells. Hum Reprod. 1998;13(1):150–3.PubMedCrossRef
31.
Zurück zum Zitat McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. Endocr Rev. 2000;21(2):200–14.PubMed McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. Endocr Rev. 2000;21(2):200–14.PubMed
32.
Zurück zum Zitat Liu L, Kong N, Xia G, Zhang M. Molecular control of oocyte meiotic arrest and resumption. Reprod Fertil Dev. 2013;25(3):463–71.PubMedCrossRef Liu L, Kong N, Xia G, Zhang M. Molecular control of oocyte meiotic arrest and resumption. Reprod Fertil Dev. 2013;25(3):463–71.PubMedCrossRef
Metadaten
Titel
Treatment of female rhesus macaques with a somatostatin receptor antagonist that increases oocyte fertilization rates without affecting post-fertilization development outcomes
verfasst von
Alison Y. Ting
Melinda J. Murphy
Pablo Arriagada
Jean-Pierre Gotteland
Jon D. Hennebold
Publikationsdatum
15.11.2018
Verlag
Springer US
Erschienen in
Journal of Assisted Reproduction and Genetics / Ausgabe 2/2019
Print ISSN: 1058-0468
Elektronische ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-018-1369-0

Weitere Artikel der Ausgabe 2/2019

Journal of Assisted Reproduction and Genetics 2/2019 Zur Ausgabe

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.