Cell-free mitochondrial DNA increases granulosa cell apoptosis and reduces aged oocyte blastocyst development in the mouse

Liu, Yu; Shen, Qiuzi; Li, Huiying; Xiang, Wenpei; Zhang, Ling

doi:10.1016/j.reprotox.2020.10.012

Cited by 9 publications

(7 citation statements)

References 38 publications

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“…Mitochondria are involved in multiple vital signaling pathways, metabolism and apoptosis, their crucial role in oocyte and early embryo development has been demonstrated in several studies using murine models [30][31][32]. The mitochondrial turnover during the early stages of embryo development is thought to be very low, and consequently mtDNA levels are expected to be stable for the first few days of life [48].…”

Section: Discussionmentioning

confidence: 99%

“…The way mitochondrial systems have evolved in animals and humans can have profound effects on healthy human reproduction [29]. A number of murine models with targeted deletion of mitochondrial-function genes resulted in infertility or subfertility showing importance of mitochondria in oocyte and early embryo development [30][31][32]. Mitochondria are inherited exclusively from the oocyte and their proliferation is highly regulated in the germline and preimplantation embryo.…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial DNA Copy Number in Cleavage Stage Human Embryos—Impact on Infertility Outcome

Podolak¹,

Liss

Kiewisz

et al. 2022

CIMB

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A retrospective case control study was undertaken at the molecular biology department of a private center for reproductive medicine in order to determine whether any correlation exists between mitochondrial DNA (mtDNA) content of cleavage-stage preimplantation embryos and their developmental potential. A total of 69 couples underwent IVF treatment (averaged women age: 36.5, SD 4.9) and produced a total of 314 embryos. A single blastomere was biopsied from each embryo at the cleavage stage (day-3 post-fertilization) subjected to low-pass next generation sequencing (NGS), for the purpose of detecting aneuploidy. For each sample, the number of mtDNA reads obtained after analysis using NGS was divided by the number of reads attributable to the nuclear genome. The mtDNA copy number amount was found to be higher in aneuploid embryos than in those that were euploid (mean mtDNA ratio ± SD: 6.3 ± 7.5 versus 7.1 ± 5.8, p < 0.004; U Mann–Whitney test), whereas no statistically significant differences in mtDNA content were seen in relation to embryo morphology (6.6 ± 4.8 vs. 8.5 ± 13.6, p 0.09), sex (6.6 ± 4.1 vs. 6.2 ± 6.8, p 0.16), maternal age (6.9 ± 7.8 vs. 6.7 ± 4.5, p 0.14) or its ability to implant (7.4 ± 6.6 vs. 5.1 ± 4.6, p 0.18). The mtDNA content cannot serve as a useful biomarker at this point in development. However, further studies investigating both quantitative and qualitative aspects of mtDNA are still required to fully evaluate the relationship between mitochondrial DNA and human reproduction.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA Copy Number in Cleavage Stage Human Embryos—Impact on Infertility Outcome

Podolak¹,

Liss

Kiewisz

et al. 2022

CIMB

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show abstract

“…To confirm the purity of granulosa cells, it was seeded and cultured on coverslips at a density of 1 × 10 5 cells/ coverslips for 48 h. Then the granulosa cells were fixed in 4% (v/v) paraformaldehyde for 20 min for immunofluorescence as before [11]. The FSH receptor (FSHR) was used to detect the purity of granulosa cells.…”

Section: Human Granulosa Cells Collection and Identificationmentioning

confidence: 99%

hsa-miR-320a-3p and hsa-miR-483-5p levels in human granulosa cells: promising bio-markers of live birth after IVF/ICSI

Liu

Mei

Yang

et al. 2022

Reprod Biol Endocrinol

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Background MicroRNAs (miRNAs) are considered potential biomarkers for various diseases. This study investigated whether hsa-miR-320a-3p and hsa-miR-483-5p levels in human ovarian granulosa cells derived from follicular fluids are associated with embryo developmental competence. Methods We collected 195 granulosa cells samples and analyzed the treatment outcomes in patients undergoing in vitro fertilization (n = 147) or intracytoplasmic sperm injection (n = 48) cycles. The hsa-miR-320a-3p and hsa-miR-483-5p levels in granulosa cells were measured using quantitative reverse transcription-polymerase chain reaction. Results Patients were subdivided into four groups according to the granulosa cells hsa-miR-320a-3p and hsa-miR-483-5p levels quartiles (Q1–Q4). Embryo developmental competence was compared using the chi-square test. Patients in Q3 were less likely to achieve a normal fertilization rate for in vitro fertilization and blastocyst formation than those in Q1 as they expressed high levels of hsa-miR-320a-3p and hsa-miR-483-5p (P < 0.05). Patients in Q3 and Q4 were less likely to achieve a good-quality embryo as they expressed high levels of hsa-miR-483-5p and hsa-miR-320a-3p (P < 0.05). The hsa-miR-320a-3p and hsa-miR-483-5p levels were not associated with clinical pregnancy. However, multiple regression analysis indicated that in Q3 and Q4 intervals had experienced a decreased chance of live birth due to high expression levels of hsa-miR-320a-3p and hsa-miR-483-5p levels. The relative hsa-miR-320a-3p expression levels in granulosa cells were weakly and positively correlated with the patient age (P = 0.0033). Moreover, both the basal follicle stimulating hormone (P = 0.0003) and ovarian stimulation protocols (P = 0.006 and P = 0.004) significantly and positively affected hsa-miR-320a-3p levels. The days of stimulation was negatively correlated with the relative hsa-miR-320a-3p expression level (P = 0.047). Conclusions The hsa-miR-320a-3p and hsa-miR-483-5p levels in human granulosa cells negatively correlated with the good-quality embryo rate and live birth, indicating that hsa-miR-320a-3p and hsa-miR-483-5p can be used as potential negative indicators to predict good-quality embryos and live births.

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“…Granulosa cells were collected from the follicular uid of 195 patients as described (19). After collection, granulosa cells were seeded and cultured on coverslips for 48 h. Then the granulosa cells were xed in 4% (v/v) paraformaldehyde for 20 min for immuno uorescence as before (20). The FSH receptor (FSHR) was used to detect the purity of granulosa cells.…”

Section: Human Granulosa Cell Collection and Identi Cationmentioning

confidence: 99%

miR-320a-3p Levels in Human Granulosa Cells: A Promising Bio-marker of Good Quality Embryo and Clinical Pregnancy after IVF/ICSI.

Liu

Mei

Shen

et al. 2021

Preprint

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BackgroundmiRNAs in body fluids are considered potential biomarkers of diseases. This study investigated whether miR-320a-3p and miR-483-5p levels in human granulosa cells from follicular fluids were associated with embryo developmental competence. MethodsWe collected 195 patients’ granulosa cells samples undergoing in vitro fertilization (n =147) or intracytoplasmic sperm injection (n =48) cycles, and gathered information about the outcomes of the treatment. miR-320a-3p and miR-483-5p levels were measured using qRT-PCR.ResultsThe miR-320a-3p levels in human granulosa cells across different patient groups were significantly different in the good quality embryo rates, with lowest levels in the Q4 intervals (P<0.05). The relative expression levels of miR-320a-3p were negatively associated with clinical pregnancy rate (P<0.05) and positively correlated with the patient age (P=0.0033). Moreover, both the basal FSH (P=0.0003) and ovarian stimulation protocol (P=0.006 and P=0.004) significantly and positively affected miR-320a-3p levels. The days of stimulation was negatively correlated with the relative expression of miR-320a-3p (P=0.0466). The relative expression levels of miR-483-5p were significantly positively correlated with AMH (P=0.0047). Neither miR-320a-3p nor miR-483-5p levels in granulosa cells were associated with normal fertilized rate, blastulation rate and abortion rate. ConclusionsThe miR-320a-3p levels in human granulosa cells were negatively correlated with the good quality embryo rate and clinical pregnancy rate and positively correlated with the patient age, indicating that miR-320a-3p can be used as a potential indicator to predict embryo development ability and clinical pregnancy.

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Cell-free mitochondrial DNA increases granulosa cell apoptosis and reduces aged oocyte blastocyst development in the mouse

Cited by 9 publications

References 38 publications

Mitochondrial DNA Copy Number in Cleavage Stage Human Embryos—Impact on Infertility Outcome

Mitochondrial DNA Copy Number in Cleavage Stage Human Embryos—Impact on Infertility Outcome

hsa-miR-320a-3p and hsa-miR-483-5p levels in human granulosa cells: promising bio-markers of live birth after IVF/ICSI

miR-320a-3p Levels in Human Granulosa Cells: A Promising Bio-marker of Good Quality Embryo and Clinical Pregnancy after IVF/ICSI.

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