Changing expression and subcellular distribution of karyopherins during murine oogenesis

Mihalas, Bettina P.; Western, Patrick; Loveland, Kate; McLaughlin, Eileen A.; Holt, Janet E.

doi:10.1530/rep-14-0585

Cited by 28 publications

(31 citation statements)

References 56 publications

(67 reference statements)

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“…Oocytes were isolated as previously described 105 . Briefly, mice between 4 to 6 weeks of age were administered intraperitoneal injections of 7.5 IU equine chorionic gonadotropin (eCG) (Intervet, Sydney NSW, Australia) to stimulate in vivo oocyte maturation to mature GV stage.…”

Section: Methodsmentioning

confidence: 99%

The lipid peroxidation product 4-hydroxynonenal contributes to oxidative stress-mediated deterioration of the ageing oocyte

Mihalas

Iuliis

Redgrove

et al. 2017

Sci Rep

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An increase in intraovarian reactive oxygen species (ROS) has long been implicated in the decline in oocyte quality associated with maternal ageing. Oxidative stress (OS)-induced lipid peroxidation and the consequent generation of highly electrophilic aldehydes, such as 4-hydroxynonenal (4-HNE), represents a potential mechanism by which ROS can inflict damage in the ageing oocyte. In this study, we have established that aged oocytes are vulnerable to damage by 4-HNE resulting from increased cytosolic ROS production within the oocyte itself. Further, we demonstrated that the age-related induction of OS can be recapitulated by exposure of germinal vesicle (GV) oocytes to exogenous H2O2. Such treatments stimulated an increase in 4-HNE generation, which remained elevated during in vitro oocyte maturation to metaphase II. Additionally, exposure of GV oocytes to either H2O2 or 4-HNE resulted in decreased meiotic completion, increased spindle abnormalities, chromosome misalignments and aneuploidy. In seeking to account for these data, we revealed that proteins essential for oocyte health and meiotic development, namely α-, β-, and γ-tubulin are vulnerable to adduction via 4-HNE. Importantly, 4-HNE-tubulin adduction, as well as increased aneuploidy rates, were resolved by co-treatment with the antioxidant penicillamine, demonstrating a possible therapeutic mechanism to improve oocyte quality in older females.

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Section: Methodsmentioning

confidence: 99%

The lipid peroxidation product 4-hydroxynonenal contributes to oxidative stress-mediated deterioration of the ageing oocyte

Mihalas

Iuliis

Redgrove

et al. 2017

Sci Rep

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“…The Karyopherin (Kpn) genes encodes importins involved in nucleo-cytoplasmic transport. Kpna7 and Kpna2 transcripts are very abundant in fully-grown oocytes of the mouse [40] and the cow (personal communication). KPNA7 interacts with other oocyte-preferential factors such as Nucleoplasmin2 in bovine and Stl3 in trout [41,42].…”

Section: Genes Highly Conserved In Fly or Distant Vertebrates And Thementioning

confidence: 99%

A Comparative Analysis of Oocyte Development in Mammals

Dalbiès-Tran

Cadoret

Desmarchais

et al. 2020

Cells

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Sexual reproduction requires the fertilization of a female gamete after it has undergone optimal development. Various aspects of oocyte development and many molecular actors in this process are shared among mammals, but phylogeny and experimental data reveal species specificities. In this chapter, we will present these common and distinctive features with a focus on three points: the shaping of the oocyte transcriptome from evolutionarily conserved and rapidly evolving genes, the control of folliculogenesis and ovulation rate by oocyte-secreted Growth and Differentiation Factor 9 and Bone Morphogenetic Protein 15, and the importance of lipid metabolism.

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“…Oocytes were isolated as described previously (113). Briefly, mice between 4 and 6 weeks of age were administered intraperitoneal injections of 7.5 IU equine chorionic gonadotropin (eCG) (Intervet, Sydney, New South Wales, Australia) to stimulate in vivo oocyte maturation to mature GV stage.…”

Section: Oocyte Collectionmentioning

confidence: 99%

Oxidative damage in naturally aged mouse oocytes is exacerbated by dysregulation of proteasomal activity

Mihalas

Bromfield

Sutherland

et al. 2018

Journal of Biological Chemistry

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An increase in oxidative protein damage is a leading contributor to the age-associated decline in oocyte quality. By removing such damaged proteins, the proteasome plays an essential role in maintaining the fidelity of oocyte meiosis. In this study, we established that decreased proteasome activity in naturally aged, germinal vesicle (GV) mouse oocytes positively correlates with increased protein modification by the lipid aldehyde 4-hydroxynonenal (4-HNE). Furthermore, attenuation of proteasome activity in GV oocytes of young animals was accompanied by an increase in 4-HNE-modified proteins, including ␣-tubulin, thereby contributing to a reduction in tubulin polymerization, microtubule stability, and integrity of oocyte meiosis. A decrease in proteasome activity was also recapitulated in the GV oocytes of young animals following exposure to oxidative insults in the form of either hydrogen peroxide (H 2 O 2 ) or 4-HNE. We also observed that upon oxidative insult, 4-HNE exhibits elevated adduction to multiple proteasomal subunits. Notably, the inclusion of the antioxidant penicillamine, to limit propagation of oxidative stress cascades, led to a complete recovery of proteasome activity and enhanced clearance of 4-HNE-adducted ␣-tubulin during a 6-h post-treatment recovery period. This strategy also proved effective in reducing the incidence of oxidative stress-induced aneuploidy following in vitro oocyte maturation, but was ineffective for naturally aged oocytes. Taken together, our results implicate proteasome dysfunction as an important factor in the accumulation of oxidatively induced protein damage in the female germline. This discovery holds promise for the design of therapeutic interventions to address the age-dependent decline in oocyte quality.

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Changing expression and subcellular distribution of karyopherins during murine oogenesis

Cited by 28 publications

References 56 publications

The lipid peroxidation product 4-hydroxynonenal contributes to oxidative stress-mediated deterioration of the ageing oocyte

The lipid peroxidation product 4-hydroxynonenal contributes to oxidative stress-mediated deterioration of the ageing oocyte

A Comparative Analysis of Oocyte Development in Mammals

Oxidative damage in naturally aged mouse oocytes is exacerbated by dysregulation of proteasomal activity

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