Ovarian Follicles Rescued 3 Days after Cyclophosphamide Treatment in Adolescent Mice: An Experimental Study Aiming at Maximizing Methods for Fertility Preservation through In Vitro Follicle Culture

Anastácio, Amandine; Waterstone, Max; Hao, Xia; Poirot, Catherine; Rodriguez‐Wallberg, Kenny A.

doi:10.3390/ijms20246190

Cited by 3 publications

(3 citation statements)

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“…Most studies included in this review used chemotherapy alkylating triggers [ 69 ] or excessive glucose stimulation [ 70 , 71 ] to establish POF models, which provide reliable and reproducible experimental conditions that mimic the pathogenesis of POF, including immune and senescence mechanisms [ 72 ]. However, it is important to note that the ovarian damage caused by cyclophosphamide is self-reversible within a certain time period [ 73 , 74 ]. Furthermore, the route of intervention significantly affects serum hormone concentrations, and differences in dissolution and metabolism can contribute to observed disparities [ 75 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of natural products on premature ovarian failure: a systematic review and meta-analysis of preclinical studies

Hu,

Zhang,

Xin

et al. 2024

J Ovarian Res

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Objective This study aims to investigate the effects of natural products on animal models of premature ovarian failure (POF). Methods We conducted comprehensive literature searches and identified relevant studies that examined the protective effects of natural products on experimental POF. We extracted quantitative data on various aspects such as follicular development, ovarian function, physical indicators, oxidative stress markers, inflammatory factors, and protein changes. The data was analyzed using random-effects meta-analyses, calculating pooled standardized mean differences and 95% confidence intervals. Heterogeneity was assessed using the I2 statistic, and bias was estimated using the SYRCLE tool. Results Among the 879 reviewed records, 25 articles met our inclusion criteria. These findings demonstrate that treatment with different phytochemicals and marine natural products (flavonoids, phenols, peptides, and alkaloids, etc.) significantly improved various aspects of ovarian function compared to control groups. The treatment led to an increase in follicle count at different stages, elevated levels of key hormones, and a decrease in atretic follicles and hormone levels associated with POF. This therapy also reduced oxidative stress (specifically polyphenols, resveratrol) and apoptotic cell death (particularly flavonoids, chrysin) in ovarian granulosa cells, although it showed no significant impact on inflammatory responses. The certainty of evidence supporting these findings ranged from low to moderate. Conclusions Phytochemicals and marine natural product therapy (explicitly flavonoids, phenols, peptides, and alkaloids) has shown potential in enhancing folliculogenesis and improving ovarian function in animal models of POF. These findings provide promising strategies to protect ovarian reserve and reproductive health. Targeting oxidative stress and apoptosis pathways may be the underlying mechanism.

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Section: Discussionmentioning

confidence: 99%

Efficacy of natural products on premature ovarian failure: a systematic review and meta-analysis of preclinical studies

Hu,

Zhang,

Xin

et al. 2024

J Ovarian Res

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“…Ovarian follicle culture was performed as previously Abbreviations: CPA, cyclophosphamide; a-MEM, a-minimal essential medium; MII, metaphase II; AMH, anti-Müllerian hormone; IVM, in vitro maturation; PFD, primordial follicle depletion; HSCT, hematologic stem cells transplantation. described (10,13,14). Briefly, selected secondary follicles were individually cultured in drops of a droplet system (20 µl per drop, 10 drops per dish) containing culture medium.…”

Section: Follicle Isolation In Vitro Culture and Maturationmentioning

confidence: 99%

“…The culture system allowed the evaluation of individual follicle growth, hormonal production, oocyte maturation, and spindle structure and chromosomal configurations in mature oocytes. To our knowledge, there is limited knowledge on the feasibility of performing fertility preservative procedures after gonadotoxic cancer treatment has been initiated, especially at prepubertal stage (9,10).…”

Section: Introductionmentioning

confidence: 99%

Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide—An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation

et al. 2021

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Ovarian tissue cryopreservation is the only feasible method for fertility preservation in prepubertal girls that will undergo gonadotoxic chemotherapy. To date, the only clinical use of cryopreserved tissue is by a later tissue retransplantation to the patient. Clinical challenges in fertility preservation of very young patients with cancer include time constraints that do not allow to retrieve the tissue for cryopreservation before starting chemotherapy and the preclusion of future ovarian tissue transplantation due to the risk of reintroduction of malignant cells in patients with systemic diseases. To overcome these two challenges, we investigated using an experimental model the feasibility of retrieving secondary follicles from ovaries of prepubertal mice after cyclophosphamide (CPA) treatment in increasing doses of 50, 75, and 100 mg/kg. The follicles were thereafter cultured and matured in vitro. The main outcomes included the efficiency of the method in terms of obtained matured oocytes and the safety of these potentially fertility preservative procedures in terms of analyses of oocyte competence regarding normality of the spindle and chromosome configurations. Our findings demonstrated that it was feasible to isolate and culture secondary follicles and to obtain mature oocytes from prepubertal mice ovaries recently treated with CPA. The efficiency of this method was highly demonstrated in the 100 mg/kg CPA group, with near 90% follicle survival rate after 12 days’ culture, similarly to control. Around 80% of the follicles met the criteria to put into maturation, and more than 40% of them achieved metaphase II, with normal spindle and chromosome configurations observed. Suboptimal results were obtained in the 50 and 75 mg/kg CPA groups. These paradoxical findings towards CPA dose might probably reflect a more difficult selection of damaged growing follicles from ovaries recently treated with lower doses of CPA and a hampered ability to identify and discard those with reduced viability for the culture.

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Feasibility of Secondary Follicle Isolation, Culture and Achievement of In-Vitro Oocyte Maturation from Superovulated Ovaries: An Experimental Proof-of-Concept Study Using Mice

Hao

Anastácio

Rodriguez‐Wallberg

2021

JCM

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Fertility preservation through ovarian stimulation, aiming at cryopreserving mature oocytes or embryos, is sometimes unsuccessful. This clinical situation deserves novel approaches to overcome infertility following cancer treatment in patients facing highly gonadotoxic treatment. In this controlled experimental study, we investigated the feasibility of in-vitro culturing secondary follicles isolated from superovulated ovaries of mice recently treated with gonadotropins. The follicle yields of superovulated ovaries were 45.9% less than in unstimulated controls. Follicles from superovulated ovaries showed faster growth pace during the initial 7 days of culture and secreted more 17β-estradiol by the end of culture vs controls. Parameters reflecting the outcome of follicular development and oocyte maturation competence in vitro were similar between superovulated and control groups, with a similar follicle size at the end of culture and around 70% survival. Nearly half of cultured follicles met the criteria for in-vitro maturation in both groups and approximately 60% of those achieved a mature MII oocyte, similarly in both groups. Over 60% of obtained MII oocytes displayed normal-looking spindle and chromosome configurations, without significant differences between the groups. Using a validated follicle culture system, we demonstrated the feasibility of secondary follicle isolation, in-vitro culture and oocyte maturation with normal spindle and chromosome configurations obtained from superovulated mice ovaries.

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Ovarian Follicles Rescued 3 Days after Cyclophosphamide Treatment in Adolescent Mice: An Experimental Study Aiming at Maximizing Methods for Fertility Preservation through In Vitro Follicle Culture

Cited by 3 publications

References 43 publications

Efficacy of natural products on premature ovarian failure: a systematic review and meta-analysis of preclinical studies

Efficacy of natural products on premature ovarian failure: a systematic review and meta-analysis of preclinical studies

Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide—An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation

Feasibility of Secondary Follicle Isolation, Culture and Achievement of In-Vitro Oocyte Maturation from Superovulated Ovaries: An Experimental Proof-of-Concept Study Using Mice

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