Title: FOXO3 and PTEN expression in the ovary of girls with extra-gonadal cancer with or
without chemotherapy treatment prior to cryopreservation
Version: 1 Date: 09 Apr 2023
Reviewer's report:
Dear authors,
Thank you for submitting your manuscript entitled "Chemotherapy treatment prior to
cryopreservation does not alter FOXO3/pFOXO3 expression in the ovarian reserve of infant/
adolescent patients with extra-gonadal cancer" for consideration.
The study examined the effects of chemotherapy on the ovarian reserve of infants and
adolescents with extra-gonadal cancer. In particular, they examined the expression of FOXO3/
pFOXO3, an important regulator of follicular growth and survival. The authors sought to
determine whether chemotherapy prior to ovarian tissue cryopreservation had an effect on
FOXO3/pFOXO3 signaling.
The study was retrospective, with data obtained from archived ovarian tissue samples from
patients who had undergone chemotherapy prior to ovarian tissue cryopreservation and controls.
The study used an established immunohistochemical staining method to assess the expression
of FOXO3/pFOXO3 in the ovarian tissue samples.
The study appears to have adhered well to the guidelines of STROBE, as the study design,
data collection methods, statistical analysis, and results were clearly described. The study also
reported potential limitations and confounding factors, such as small sample size, heterogeneity
of cancer types, and lack of follow-up data.
The results of the study showed that there was no significant difference in the expression of
FOXO3/pFOXO3 in ovarian tissue samples between patients who had received chemotherapy
and those who had not. This suggests that chemotherapy treatment prior to ovarian tissue
cryopreservation has no adverse effects on FOXO3/pFOXO3 signaling in the ovarian reserve of
childhood/adolescent patients with extra-gonadal cancer.
Overall, the study provides valuable insights into the effects of chemotherapy on ovarian reserve
in young female cancer patients. The study is well designed and conducted and contains a clear
presentation of the methods and results.
I have few suggestions for improvement before it can be considered for publication:
First, some papers in the literature provide a good overview of the current understanding
of chemotherapy-induced ovarian damage, which would be a useful addition to your
introduction. I suggest you refer to "Bedoschi GM, Navarro PA, Oktay KH. Novel insights
into the pathophysiology of chemotherapy-induced damage to the ovary. Panminerva Med.
2019;61(1):68-75. doi:10.23736/S0031-0808.18.03494-8" in the Introduction section.
Second, it would be helpful to provide more information in the introduction about FOXO3
and PTEN, genes known to regulate ovarian primordial follicle quiescence/activation. This
information would help the reader understand the significance of the FOXO3/pFOXO3
expression analysis performed in this study.
Overall, I think this is an interesting study that makes a valuable contribution to the literature
on chemotherapy-induced ovarian damage. With the suggested revisions, I believe it could be
suitable for publication in a peer-reviewed journal.
Sincerely,