Elevated intracellular pH appears in aged oocytes and causes oocyte aneuploidy associated with the loss of cohesion in mice

Cheng, Jinmei; Li, Jian; Tang, Ji‐Xin; Chen, Su‐Ren; Deng, Shoulong; Jin, Cheng; Zhang, Yan; Wang, Xiuxia; Zhou, Chenxi; Liu, Yi‐Xun

doi:10.1080/15384101.2016.1201255

Cited by 23 publications

(13 citation statements)

References 51 publications

(100 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As the spindle assembly checkpoint (SAC) prevents chromatid separation until the proper attachment of sister chromatids on the mitotic spindle is accomplished, defects in the SAC can also cause a significant increase in aneuploidy rate [47,48]. One study observed that the aneuploidy rate in oocytes of aged mice was 31.6%, whereas the rate in young mice was 4.9% [49]. Telomere shortening commonly exists in aged oocytes mainly due to an aginginduced increase in the ROS content of the cells [24,50] and has been shown to contribute to the DNA damage response [51].…”

Section: Genetic Changesmentioning

confidence: 99%

The Molecular Regulation in the Pathophysiology in Ovarian Aging

Lin

Tsai

et al. 2021

Aging and disease

View full text Add to dashboard Cite

The female reproductive system is of great significance to women's health. Aging of the female reproductive system occurs approximately 10 years prior to the natural age-associated functional decline of other organ systems. With an increase in life expectancy worldwide, reproductive aging has gradually become a key health issue among women. Therefore, an adequate understanding of the causes and molecular mechanisms of ovarian aging is essential towards the inhibition of age-related diseases and the promotion of health and longevity in women. In general, women begin to experience a decline in ovarian function around the age of 35 years, which is mainly manifested as a decrease in the number of ovarian follicles and the quality of oocytes. Studies have revealed the occurrence of mitochondrial dysfunction, reduced DNA repair, epigenetic changes, and metabolic alterations in the cells within the ovaries as age increases. In the present work, we reviewed the possible factors of aging-induced ovarian insufficiency based on its clinical diagnosis and performed an in-depth investigation of the relevant molecular mechanisms and potential targets to provide novel approaches for the effective improvement of ovarian function in older women.

show abstract

Section: Genetic Changesmentioning

confidence: 99%

The Molecular Regulation in the Pathophysiology in Ovarian Aging

Lin

Tsai

et al. 2021

Aging and disease

View full text Add to dashboard Cite

show abstract

“…Our lab shows that aged oocytes have a high intracellular pH value (pHi) and loss of cohesion occurs when young oocytes have a high pHi. Thus, we inferred that dysregulation of pHi in aged oocytes might damage protein–protein binding affinity or protein localization of cohesion subunits, which leads to deterioration of chromosome cohesion [ 2 ] ( Figure 2 B), but the specific mechanism remains unknown. Other factors might also contribute to cohesion deterioration, such as spontaneous hydrolysis of peptide bonds, cohesion deacetylases and releasins.…”

Section: The Cause Of Age-related Loss Of Cohesionmentioning

confidence: 99%

“…Numerous studies have reported that the aneuploid rate in oocytes increases along with maternal age [ 2 , 3 , 4 , 5 , 6 ]. For example, Cheng et al observed that the incidence of aneuploidy in older mice (31.6%, 12 months) was significantly increased compared with young mice (4.9%, 1 month) [ 2 ]. Merriman et al found that this rate could reach up to 60% in 15 month old mice [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Age-Related Loss of Cohesion: Causes and Effects

Cheng

Liu

2017

IJMS

Self Cite

View full text Add to dashboard Cite

Aneuploidy is a leading genetic cause of birth defects and lower implantation rates in humans. Most errors in chromosome number originate from oocytes. Aneuploidy in oocytes increases with advanced maternal age. Recent studies support the hypothesis that cohesion deterioration with advanced maternal age represents a leading cause of age-related aneuploidy. Cohesin generates cohesion, and is established only during the premeiotic S phase of fetal development without any replenishment throughout a female’s period of fertility. Cohesion holds sister chromatids together until meiosis resumes at puberty, and then chromosome segregation requires the release of sister chromatid cohesion from chromosome arms and centromeres at anaphase I and anaphase II, respectively. The time of cohesion cleavage plays an important role in correct chromosome segregation. This review focuses specifically on the causes and effects of age-related cohesion deterioration in female meiosis.

show abstract

“…When the culture dishes are removed from the incubator to the water bath, the CO 2 content drops from 5% to 0.038%, causing an immediate pH change of the medium. It is obvious that pH should be maintained within the physiological range during maturation to ensure cell function (Cheng et al, 2016). Oocytes have limited capacity to regulate their internal pH and so must depend on the pH of the external environment (Krisher, 2013).…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic responses of porcine cumulus cells to heat exposure during oocytes in vitro maturation

Liu

Yin

et al. 2020

Molecular Reproduction Devel

View full text Add to dashboard Cite

The oocyte is vulnerable to various environmental stressors, including heat exposure. Cumulus-oocyte complexes (COCs) comprise functional units for oocytes in vitro maturation, and the cumulus cells provide essential supports and protect the oocyte from environmental insults. Heat exposure results in varied consequences in oocyte, presumably due to different responses of cumulus cells to heat exposure. In this study, we examined whether heat exposure of different duration affects porcine oocytes quality differently, and how such effects, if any, relate to transcriptomic profiles of cumulus cells. COCs were heat-exposed for 4 h (20-24 h, COC4) and 24 h (0-24 h, COC24), respectively, and the quality of oocytes in COC24 group showed significantly impaired with disrupted cumulus expansion and extracellular matrix (ECM) structure. The transcriptomic analysis identified 749 and 1238 differential expression genes (DEGs) in COC4 and COC24, respectively. Moreover, 852 DEGs were found when COC24 was compared with COC4, and the downregulated DEGs were mainly associated with Gene Ontology terms linked with ECM and cell proliferation. In the protein-protein interaction network, HSPE1, TNFAIP6, COL12A1, and COL18A1 were identified as hub genes playing important roles in heat-induced transcriptomic responses. These results indicate that impaired cumulus proliferation and ECM structure are responsible for heat-induced damage in oocytes quality. K E Y W O R D S cumulus cells, heat exposures, pig, transcriptomes 1 | INTRODUCTION Oocytes are surrounded by multilayered cumulus cells (CCs) to form cumulus-oocyte complex (COC), a functional unit for oocyte maturation. COCs can be cultured in vitro for oocytes maturation, and porcine oocytes usually require 42-48 h to reach metaphase II in culture. Cumulus cells are essential in the maturation process of oocytes, not only transmit bioactive substances and energy materials to oocytes, but also protect the oocytes from the interference of the external environment (Gilchrist et al., 2004). During oocytes maturation, cumulus cells proliferate, differentiate, and communicate with each other via extracellular matrix (ECM) and through gap junctions (Campen et al., 2018), adherens (Mora et al., 2012), and tight junctions (Clelland & Kelly, 2010). They also send transzonal projections (Yin et al., 2019) to interact with the enclosed oocyte. ECM not only provides a physical scaffold for cell-cell interactions, but also plays a key role in normal follicular growth, oocyte development, ovulation, and luteinization (Kimura et al., 2007). Oocytes are susceptible to various environmental stresses, including heat exposure. Heat-induced alterations in oocyte quality depend on timing, duration, and the extent of the exposure. For instance, COCs aspirated from multiparous Holstein cows in cold (December-April) seasons had a higher cleavage and blastocyst rates than in hot (May-September) seasons (Gendelman & Roth, 2012).

show abstract

Elevated intracellular pH appears in aged oocytes and causes oocyte aneuploidy associated with the loss of cohesion in mice

Cited by 23 publications

References 51 publications

The Molecular Regulation in the Pathophysiology in Ovarian Aging

The Molecular Regulation in the Pathophysiology in Ovarian Aging

Age-Related Loss of Cohesion: Causes and Effects

Transcriptomic responses of porcine cumulus cells to heat exposure during oocytes in vitro maturation

Contact Info

Product

Resources

About