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P-393 The mitochondrial targeted antioxidant Mitoquinol increases survival of isolated human preantral follicles in vitro
Abstract Study question Does Mitoquinol have a protective effect on survival and mitochondrial oxidative stress in cultured human preantral follicles? Summary answer Mitoquinol significantly increased survival of human preantral follicles cultured for 8 days and significantly decreased expression of...
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| Published in: | Human reproduction (Oxford) 2023-06, Vol.38 (Supplement_1) |
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| Main Authors: | , , , , , , |
| Format: | Article |
| Language: | English |
| Online Access: | Get full text |
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| Summary: | Abstract
Study question
Does Mitoquinol have a protective effect on survival and mitochondrial oxidative stress in cultured human preantral follicles?
Summary answer
Mitoquinol significantly increased survival of human preantral follicles cultured for 8 days and significantly decreased expression of genes related to the mitochondrial oxidative stress response.
What is known already
Culturing human ovarian follicles is a promising new source of mature oocytes for fertility preservation, as well as a key model system to investigate fundamental biology. Nevertheless, only a handful of studies have yielded mature human oocytes from preantral stage follicles and optimizing culture systems is challenging due to the scarcity of human material. Mitoquinol is an antioxidant that contains a form of Coenzyme Q10 called ubiquinone that has been modified to selectively target and protect mitochondria from oxidative damage. In human oocytes, the presence of Mitoquinol in the IVM media increased nuclear maturation and protected against chromosomal misalignment.
Study design, size, duration
Human preantral follicles (n = 213; mean diameter: 71 µm; range: 26-189 µm) were isolated from ovarian medulla tissue. Preantral follicles were mechanically and enzymatically isolated, encapsulated in 0.5% alginate and cultured for 8 days in three experimental groups: Control (n = 68); 50nM Mitoquinol (n = 71), 250nM Mitoquinol (n = 74). The primary endpoints were follicular growth and survival. Secondary endpoints included follicular gene expression and hormone analysis of the spent culture media.
Participants/materials, setting, methods
Ovarian medulla tissue was donated by 5 patients (aged 30-37 years) undergoing unilateral oophorectomy for ovarian tissue cryopreservation. Follicular growth and survival were assessed every second day during culture by microscopy. For follicles bigger than 95 µm, AMH and Estradiol concentrations were measured by ELISA in the spent media on day 8. Finally surviving follicles were snap-frozen and gene expression was analysed by qPCR; mitochondrial oxidative stress genes: HSP-60, TFAM and apoptosis genes: BAX/BCL-2.
Main results and the role of chance
After 8 days in culture, the follicular survival rate in the 50nM Mitoquinol group (68%; n = 51/74) was significantly higher than the control group (49%; n = 32/68; p = 0.0344) and the 250nM Mitoquinol (54%; n = 39/71; p = 0.0443). The protective effect of 50nM Mitoquinol was more pronounced in the subset |
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| ISSN: | 0268-1161 1460-2350 |
| DOI: | 10.1093/humrep/dead093.745 |