Embryo quality, and not chromosome nondiploidy, affects mitochondrial DNA content in mouse blastocysts

Jing, Ying; Li, Li; Li, Yuanyuan; Ouyang, Ying‐Chun; Sun, Qing‐Yuan; Zhang, Cuilian; Li, Rong

doi:10.1002/jcp.27713

Cited by 9 publications

(8 citation statements)

References 35 publications

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“…In our previous study, in vivo‐derived embryos had lower Mt‐DNA copy numbers than in vitro‐developed embryos (Noguchi, et al., 2020). In addition, positive pregnancy outcomes in humans are more common using blastocysts with low Mt‐DNA copy numbers (Diez‐Juan et al., 2015; Fragouli et al., 2015; Jing et al., 2019). Furthermore, low‐quality oocytes resulted in blastocysts containing higher Mt‐DNA copy numbers in mice (Jing et al., 2019).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, positive pregnancy outcomes in humans are more common using blastocysts with low Mt‐DNA copy numbers (Diez‐Juan et al., 2015; Fragouli et al., 2015; Jing et al., 2019). Furthermore, low‐quality oocytes resulted in blastocysts containing higher Mt‐DNA copy numbers in mice (Jing et al., 2019). In this study, blastocysts developed on XG‐LBG gel had higher cell numbers but similar Mt‐DNA content than blastocysts developed without gel.…”

Section: Discussionmentioning

confidence: 99%

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Xanthan gum and locust bean gum substrate improves bovine embryo development

Hara

Aoki

Nagata

et al. 2020

Reprod Domestic Animals

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One of the major difference between the in vivo and in vitro embryonic environments is the stiffness of the culture substrate. Xanthan gum (XG) and locust bean gum (LBG) are natural materials that are safe, inexpensive and easy to handle. In this study, we investigated the effects of using a polysaccharide culture substrate made from 1% XG and 1% LBG (XG‐LBG gel) on bovine embryonic development. Oocytes collected from bovine ovaries were subjected to maturation, and fertilization to generate embryos at an early developmental stage (>4 cell stage). Cleaved embryos were further cultured in a well of 96‐well cell culture plate coated with or without XG‐LBG gel for 5 days. While the developmental rate up to the blastocyst stage did not differ between the two culture systems (control, 38.0 vs. gel, 38.6%), blastocysts developed on the XG‐LBG gel produced significantly high cell numbers and ATP content. Embryos cultured on XG‐LBG gels for 24 hr had high expression levels of F‐actin and a highly even distribution of E‐cadherin. In addition, embryos developed on XG‐LBG gel demonstrated increased translocation of YAP to the nucleus and increased connective tissue growth factor (CTGF) protein levels (downstream of Hippo signalling). These findings suggest that soft culture substrates improve embryonic development by enhancing mechanotransduction, including YAP‐CTGF signalling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Xanthan gum and locust bean gum substrate improves bovine embryo development

Hara

Aoki

Nagata

et al. 2020

Reprod Domestic Animals

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“…However, the relationship between mitochondrial number and reproductive potential in blastocysts is not completely clear. Accumulating evidence supports the quiet embryo hypothesis [12], which states that blastocysts with higher mitochondrial DNA copy numbers have low quality or low reproductive ability [13][14][15][16].…”

Section: Introductionmentioning

confidence: 85%

Mitochondrial reactive oxygen species regulate mitochondrial biogenesis in porcine embryos

Kageyama

Ito

Shirasuna

et al. 2021

Journal of Reproduction and Development

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The number of mitochondria in blastocysts is a potential marker of embryo quality. However, the molecular mechanisms governing the mitochondrial number in embryos are unclear. This study was conducted to investigate the effect of reduced mitochondrial reactive oxygen species (ROS) levels on mitochondrial biogenesis in porcine embryos. Oocytes were collected from gilt ovaries and activated to generate over 4 cell-stage embryos at day 2 after activation. These embryos were cultured in media containing either 0.1 µM MitoTEMPOL (MitoT), 0.5 µM Mitoquinol (MitoQ), or vehicle (ethanol) for 5 days to determine the rate of development to the blastocyst stage. The mitochondrial number in blastocysts was evaluated by real-time polymerase chain reaction (PCR). Five days after activation, the embryos (early morula stage) were subjected to immunostaining to determine the expression levels of NRF2 in the nucleus. In addition, the expression levels of PGC1α and TFAM in the embryos were examined by reverse transcription PCR. One day of incubation with the antioxidants reduced the ROS content in the embryos but did not affect the rate of development to the blastocyst stage. Blastocysts developed in medium containing MitoT had lower mitochondrial DNA copy numbers and ATP content, whereas MitoQ showed similar but insignificantly trends. Treatment of embryos with either MitoT or MitoQ decreased the expression levels of NRF2 in the nucleus and levels of PGC1α and TFAM. These findings indicate that reductions in mitochondrial ROS levels are associated with low mitochondrial biogenesis in embryos.

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“…Cytoplasm mitochondrial DNA copy number is often seen among aneuploid embryos [31], and this has been found to correspond to a relatively low chance of producing an ongoing pregnancy [32]. If enhanced oxygen perfusion after intraovarian injection of platelet-derived growth factors results in improved intrafollicular oxygen and better ooplasm quality, then the subsequent recovery of mitochondrial function could be another pathway by which ploidy rescue of blastocysts is attained.…”

Section: De Novo Oocytesmentioning

confidence: 99%

Intraovarian vascular enhancement via stromal injection of platelet-derived growth factors: Exploring subsequent oocyte chromosomal status and in vitro fertilization outcomes

Wood

Sills

2020

Clin Exp Reprod Med

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The inverse correlation between maternal age and pregnancy rate represents a major challenge for reproductive endocrinology. The high embryo ploidy error rate in failed <i>in vitro</i> fertilization (IVF) cycles reflects genetic misfires accumulated by older oocytes over time. Despite the application of different follicular recruitment protocols during IVF, gonadotropin modifications are generally futile in addressing such damage. Even when additional oocytes are retrieved, quality is frequently poor. Older oocytes with serious cytoplasmic and/or chromosomal errors are often harvested from poorly perfused follicles, and ovarian vascularity and follicular oxygenation impact embryonic chromosomal competency. Because stimulation regimens exert their effects briefly and immediately before ovulation, gonadotropins alone are an ineffective antidote to long-term hypoxic pathology. In contrast, the tissue repair properties (and particularly the angiogenic effects) of platelet-rich plasma (PRP) are well known, with applications in other clinical contexts. Injection of conventional PRP and/or its components (e.g., isolated platelet-derived growth factors as a cell-free substrate) into ovarian tissue prior to IVF has been reported to improve reproductive outcomes. Any derivative neovascularity may modulate oocyte competence by increasing cellular oxygenation and/or lowering concentrations of intraovarian reactive oxygen species. We propose a mechanism to support intrastromal angiogenesis, improved follicular perfusion, and, crucially, embryo ploidy rescue. This last effect may be explained by mRNA upregulation coordinated by PRP-associated molecular signaling, as in other tissue systems. Additionally, we outline an intraovarian injection technique for platelet-derived growth factors and present this method to help minimize reliance on donor oocytes and conventional hormone replacement therapy.

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Embryo quality, and not chromosome nondiploidy, affects mitochondrial DNA content in mouse blastocysts

Cited by 9 publications

References 35 publications

Xanthan gum and locust bean gum substrate improves bovine embryo development

Xanthan gum and locust bean gum substrate improves bovine embryo development

Mitochondrial reactive oxygen species regulate mitochondrial biogenesis in porcine embryos

Intraovarian vascular enhancement via stromal injection of platelet-derived growth factors: Exploring subsequent oocyte chromosomal status and in vitro fertilization outcomes

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