Early prepubertal cyclophosphamide exposure in mice results in long-term loss of ovarian reserve, and impaired embryonic development and blastocyst quality.

BackgroundDue to improved treatment, there is an increasing focus on the reproductive potential of survivors of childhood cancer. Cytotoxic chemotherapy accelerates the decline in the number of primordial follicles within the mammalian ovary at all ages, but effects on the developmental potential of remaining oocytes following prepubertal cancer treatment are unclear.ObjectivesTo investigate whether cyclophosphamide (CY) exposure in the prepubertal period in female mice influences ovarian function and the functional competence of oocytes in adulthood.MethodsThis study used Swiss albino mice as the experimental model. Female mice were treated with 200 mg/kg CY on either postnatal day 14 (CY14), 21 (CY21) or 28 (CY28) i.e at a prepubertal and 2 young postpubertal ages. At 14 weeks of life, ovarian function, functional competence of oocytes, and embryo quality were assessed.ResultsThe number of primordial follicles decreased significantly in CY14 and CY21 groups compared to control (p ConclusionOur results indicate long-term effects on the developmental competence of oocytes exposed to CY in early but not adult life. These data provide a mechanism whereby long-term fertility can be impaired after chemotherapy exposure, despite the continuing presence of follicles within the ovary, and support the need for fertility preservation in prepubertal girls before alkylating agent exposure

Representative figure of 1D ¹H NMR spectrum of the one-step embryo culture medium used in this study.

The figure elucidates the assignment of peaks for different metabolites. X-axis represents the chemical shift in parts per million.</p

Comparison of the relative intensities of SCM metabolites (normalized to TSP) with TUNEL index.

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Principal component analysis bi-plot for comparing the relative metabolite intensities of IVF and ICSI derived sibling embryos.

PCA plot (PC1 vs PC2) of SCM demonstrated random distribution of metabolites between IVF and ICSI derived embryos. Each dot represents a single sample. Blue dots (●) represents IVF derived SCM whereas orange dots (●) represents ICSI derived SCM.</p

Principal component analysis bi-plot of the relative metabolite intensities of IVF and ICSI derived sibling embryos in relation to paternal factors.

A) Bi-plot (PC1 vs PC2) of relative metabolite intensities of IVF and ICSI derived embryos in relation to sperm head defects did not demonstrate differential clustering. Blue dots (●) represents 15% sperm head defects from IVF; whereas grey dots (●) represents 15% sperm head defects from ICSI. B) Bi-plot (PC1 vs PC2) of relative metabolite intensity of IVF and ICSI embryos in relation to TUNEL index showed random distribution of data points. Blue dots (●) represents 10% TUNEL index category from IVF group; grey dots (●) represents 10% TUNEL index category from ICSI group.</p

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Comparison of the relative intensities between IVF and ICSI derived embryo SCM metabolites (normalized to TSP) along with medium control metabolites.

Data represented in mean ± SD.</p

Patient’s demographics and clinical characteristics.

Patient’s demographics and clinical characteristics.</p

Embryological characteristics.

Embryological characteristics.</p