Phosphodiesterase 3 inhibitors suppress oocyte maturation and consequent pregnancy without affecting ovulation and cyclicity in rodents.

Wiersma, A.; Hirsch, Barry E.; Tsafriri, A.; Hanssen, Robert G.J.M; Kant, Melis; Kloosterboer, H.J.; Conti, Marco; Hsueh, Aaron J. W.

doi:10.1172/jci2566

Cited by 116 publications

(68 citation statements)

References 33 publications

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“…Several years later, activity of the oocyte PDE3 was shown to increase before both spontaneous and gonadotrophin-induced meiotic resumption (Richard et al 2001). The effect of specific PDE3 inhibitors on maintaining oocyte meiotic arrest in vitro has now been demonstrated across many mammalian species: rats (Tsafriri et al 1996), mice (Wiersma et al 1998), cattle (Mayes & Sirard 2002, Thomas et al 2002, monkeys (Jensen et al 2002), humans (Nogueira et al 2003a) and swine (Laforest et al 2005). Demonstration of sterility of female mice bearing a PDE3A-null mutation due to the ovulation of GV-stage oocytes was the final proof of the central role of PDE3A in maintaining oocyte meiotic arrest (Masciarelli et al 2004).…”

Section: Cgmp and Phosphodiesterasesmentioning

confidence: 99%

Oocyte maturation and quality: role of cyclic nucleotides

Gilchrist¹,

Luciano²,

Richani³

et al. 2016

Reproduction

173

127

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The cyclic nucleotides, cAMP and cGMP, are the key molecules controlling mammalian oocyte meiosis. Their roles in oocyte biology have been at the forefront of oocyte research for decades, and many of the long-standing controversies in relation to the regulation of oocyte meiotic maturation are now resolved. It is now clear that the follicle prevents meiotic resumption through the actions of natriuretic peptides and cGMP -inhibiting the hydrolysis of intra-oocyte cAMP -and that the pre-ovulatory gonadotrophin surge reverses these processes.

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Section: Cgmp and Phosphodiesterasesmentioning

confidence: 99%

Oocyte maturation and quality: role of cyclic nucleotides

Gilchrist¹,

Luciano²,

Richani³

et al. 2016

Reproduction

173

127

View full text Add to dashboard Cite

show abstract

“…Soluble forms of PDE3A exist in oocytes (Shitsukawa et al 2001), but the mechanisms of activation of the PDE3A remain unknown. Studies aiming to develop a new contraceptive strategy have shown that inhibition of PDE3A blocks oocyte meiosis in several species in vivo and in vitro (Tsafriri et al 1996, Wiersma et al 1998, Jensen et al 2002, Mayes & Sirard 2002, Nogueira et al 2003a.…”

Section: Introductionmentioning

confidence: 99%

Effects of long-term in vitro exposure to phosphodiesterase type-3 inhibitors on follicle and oocyte development

Nogueira¹,

Cortvrindt²,

Everaerdt³

et al. 2005

Reproduction

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Germinal vesicle (GV)-stage oocytes retrieved from antral follicles undergo nuclear maturation in vitro, which typically occurs prior to cytoplasmic maturation. Short-term culture with meiotic inhibitors has been applied to arrest oocytes at the GV stage aiming to synchronize nuclear and ooplasmic maturity. However, the results obtained are still far from the in vivo situation. In order to acquire competence, immature oocytes may require meiotic arrest in vitro for a more extended period. The phosphodiesterase type 3-inhibitor (PDE3-I) is a potent meiotic arrester. The effects of a prolonged culture with PDE3-I on oocyte quality prior to and after reversal from the inhibition are not known. This study tested the impact of long-term in vitro exposure of two PDE3-Is, org9935 and cilostamide, on oocytes using a mouse follicle culture model. The results showed that PDE3-I (maximum of 10 mM) during a 12-day culture of follicle-enclosed oocytes did not alter somatic cell proliferation, differentiation or follicle survival. In addition, the steroid production profile was not significantly modified by a 12-day exposure to PDE3-I. The recombinant human chorionic gonadotrophin/recombinant human epidermal growth factor stimulus induced a characteristic normal progesterone peak of luteinization and normal mucification of the cumulus cells, while the enclosed oocyte remained blocked at the GV stage. In vitro maturation of denuded or cumulus-enclosed oocytes derived from org9935-or cilostamide-exposed follicles progressed through meiosis and formed morphologically normal meiotic spindles with chromosomes properly aligned at the equator. In conclusion, long-term culture with PDE3-I was harmless to somatic cell function, differentiation, oocyte growth and maturation. Our results suggested that PDE3-I can be applied when extended oocyte culture is required to improve ooplasmic maturation.

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“…The PDE3A activity in the regulation of oocyte maturation of several species has been studied extensively e.g. in rodent (Wiersma et al 1998), rat (Richard et al 2001), mouse (Masciarelli et al 2004;Nogueira et al 2003b;Nogueira et al 2005), monkey , porcine (Sasseville et al 2006;Sasseville et al 2007), bovine (Mayes and Sirard 2002;Thomas et al 2002), and human (Nogueira et al 2003a). Various PDE3 inhibitors were used like org9935, cilostamide, or milrinone.…”

Section: Phosphodiesterase 3a (Pde3a)mentioning

confidence: 99%