Activation of the cGMP signaling pathway is essential in delaying oocyte aging in diabetes mellitus

Anuradha P. Goud, Pravin T. Goud, Michael Peter Diamond, Bernard Gonik, Husam M. Abu-Soud

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Uncontrolled diabetes mellitus (DM) adversely affects oocyte maturation and embryo development via mechanisms that are yet unclear. Nonetheless, DM may cause uncoupling of nitric oxide synthases (NOSs) with reduction in the bioavailability of nitric oxide (NO), which is critical to maintain oocyte viability and prevent aging. The current study investigates the role of NO-mediated signaling related to oocyte aging in diabetic and nondiabetic mice. Age-related alterations in the oocytes, including ooplasmic microtubule dynamics (OMD), cortical granule (CG) status, and zona pellucida (ZP) hardening as well as the integrity of the spindle/chromatin were studied using confocal microscopy. Oocytes obtained from diabetic mice exhibited accelerated aging compared to that from nondiabetic mice. Moreover, oocytes from diabetic animals were exquisitely sensitive to NOS and guanylate cyclase (GC) inhibitors (L-NAME, ODQ), which induced aging and relatively resistant to its delay by the cGMP derivative (8-Br-cGMP). Oocytes from nondiabetic control mice displayed similar sensitivity to L-NAME in older oocytes, although to a significantly lower extent than that of DM (P < 0.04-0.0001). Despite the differences in response between DM and nonDM mice, the activation of cGMP pathway is essential to maintain the integrity of oocytes and delay oocyte aging. These findings not only indicate the role of NO signaling in the prevention of oocyte aging but also suggest enhanced aging and NO insufficiency in oocytes from diabetic mice. A comprehensive model incorporating our current findings with NOS, GC, and G kinase cycles is presented.

Original languageEnglish (US)
Pages (from-to)11366-11378
Number of pages13
JournalBiochemistry
Volume45
Issue number38
DOIs
StatePublished - Sep 26 2006
Externally publishedYes

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Medical problems
Oocytes
Diabetes Mellitus
Aging of materials
Chemical activation
Nitric Oxide
Nitric Oxide Synthase
Guanylate Cyclase
NG-Nitroarginine Methyl Ester
Cyclic GMP-Dependent Protein Kinases
Confocal microscopy
Chromatin
Hardening
Guanylate Kinases
Animals
Zona Pellucida
Derivatives
Confocal Microscopy
Microtubules
Biological Availability

ASJC Scopus subject areas

  • Biochemistry

Cite this

Activation of the cGMP signaling pathway is essential in delaying oocyte aging in diabetes mellitus. / Goud, Anuradha P.; Goud, Pravin T.; Diamond, Michael Peter; Gonik, Bernard; Abu-Soud, Husam M.

In: Biochemistry, Vol. 45, No. 38, 26.09.2006, p. 11366-11378.

Research output: Contribution to journalArticle

Goud, Anuradha P. ; Goud, Pravin T. ; Diamond, Michael Peter ; Gonik, Bernard ; Abu-Soud, Husam M. / Activation of the cGMP signaling pathway is essential in delaying oocyte aging in diabetes mellitus. In: Biochemistry. 2006 ; Vol. 45, No. 38. pp. 11366-11378.
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