Ferroptosis: A Novel Type of Cell Death in Male Reproduction
, Zelan Liu 1,†, Keyu Xie 1, Yingxin Ren 1, Chunyun Li 1,2,* and Wei Chen 1,3,*Round 1
Reviewer 1 Report
Ferroptosis reviewer report
My comments on this paper are mainly editorial; the science information itself generally seems fine. However, in Table 1, the authors need to give more information as to how they know that there are ‘ferroptosis-related morphological characteristics’ (and therefore potentially a ferroptosis process occurring) for those agents where there is no available data for ‘gross changes’ or for ‘sub-microscopic changes’, and only non-specific ones in ‘microscopic morphology changes’.
By their nature of collating information from the literature, reviews are often not easy for a non-specialist to read. While this review seems to be comprehensive, unfortunately the reading of it is made doubly-difficult by the multitude of English language errors. The authors must now, and in any future paper before submitting for review, ask a good English speaker to read through their manuscript and make appropriate language corrections.
In several places the meaning of a sentence is ambiguous and is occasionely even in danger of being interpreted opposite to the meaning intended. In most cases this is due to missing words, or it not being clear from the text how additional clauses fit in.
I have picked out and listed in the Table below (and attached as a pdf) over 70 places where the language needs correcting.
|
Line |
Present text |
Suggested revised text |
Comment |
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|
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29 |
hotpot |
hotspot |
|
|
31 |
Once certain processes disorder presents |
|
English - not sure what is meant here; needs rewriting |
|
32 |
barriers of glutathione |
(?) barriers to glutathione |
(?) |
|
33 |
ROS |
ROS (reactive oxygen species – which are…..) |
Need to clarify this abbreviation here. If it is ‘Reactive oxygen species’ – also indicate what these are. |
|
34-35 |
general process composed with various mechanism |
General process arising from various mechanisms |
|
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37-38 |
it has also been proved |
|
This needs a reference |
|
38-40 |
Different factors induce ferroptosis resulting in morphological structure or functional dysfunction of reproductive cells, which is closely related to the occurrence of related diseases, such as male azoospermia and oligospermia |
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This needs a reference |
|
57 |
BJ-derived |
|
Define ‘BJ’ |
|
59 |
which induce a particular cell death |
which induces a particular process of cell death |
I presume the authors mean ’a particular type of process of cell death’ rather than ‘death of a particular cell type’ |
|
62-63 |
as classic ferroptosis agonists by |
as a classic ferroptosis agonist by |
Singular, not plural |
|
68-69 |
the functions and mechanisms of ferroptosis continue to be deepened and updated. |
our appreciation of the depth of the functions and mechanisms of ferroptosis continues to be updated. |
|
|
75 |
in details |
In detail |
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76 |
swearing |
sweating (??) |
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80 |
can be seen in ferroptotic cells compared to normal cells |
Either: …can be seen more in ferroptotic cells, compared to normal cells… OR ‘…can be seen in ferroptotic cells, but not in normal cells’. |
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|
84 |
Nowadays, |
|
New paragraph |
|
85 |
with the company of rising diseases. |
with the rising number of associated diseases |
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|
90 |
organ, |
organs, |
|
|
93 |
It is very promising |
Potentially, It will be very promising |
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97Table 1 |
N.A. for gross changes and morphology changes. |
|
If the only changes are non-specific ones in Microscopic Morphology (as with ‘Smoking’), how do the authors know these are ferroptosis-related ? |
|
116 & 118 |
irons |
ions |
|
|
119 |
sixtransmembrane epithelial antigen |
Do the authors mean: |
Please check and clarify |
|
119 |
the prostate member 3 (STEAP3). |
STEAP3 what ? ... eg. STEAP3 gene ?? or 'metalloreductase enzyme ? |
Member ?? Please recheck what is the correct term in full here. Are they referring to a protein or a gene ? |
|
120 |
Following, Fe2+ |
Following this, Fe2+ |
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128 |
clusters synthesis[ |
cluster synthesis |
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138 & 143 |
spermatocyte….. |
spermatocytes |
All should be plural |
|
138 & 139 & 140 |
spermatid |
spermatids |
All should be Plural |
|
140-141 |
Sertoli cells stores |
store |
Singular |
|
142-143 |
could be supplemented, which is taken in by |
|
Is ‘supplemented’ the correct word ? . It could either mean ‘added to by something else’ (in which case the authors should say by what), or ‘added to by more iron’ The authors need to clarify this. |
|
143 |
which is |
Do the authors mean: ‘and is’ ?? |
|
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153 |
Degradation of the only export FPN |
What do the authors mean by : ‘the only export ferroportin ?’ Is it the only export from the cell, or the only exporter carrying iron ? Should 'export' be 'exporter' ? |
|
|
164 |
lead to |
leads to - present tense led to - past tense Which do the authors wish to use ? |
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168-169 |
sperm abnormalities including sperm vitality and progressive motility |
including problems with sperm abnormalities, such as sperm vitality…. |
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170-171 |
models, studying… |
models, made for studying… OR models, which replicate or mimic…. |
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|
180-181 |
mentioned in morphologic features (Table 1.) |
mentioned in Table 1. |
|
|
182 |
DFO |
?? desferrioxamine (DFO) |
DFO abbreviation needs indicating in full |
|
186 |
TM4 cells, testicular Sertoli cells |
TM4 cells, and in testicular Sertoli cells…. |
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|
188 |
pm2.5[13]. |
pm2.5 [13] |
Please also indicate what is pm2.5. |
|
191 |
Round spermatids appeared iron-dependent cell death |
Round spermatids showed (?? or ‘revealed’ ?, or ‘appeared to show’) iron-dependent…. |
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|
211 |
and inhibiting it such as using iron |
and inhibiting it, such as by using iron……FPN, is likely….. |
|
|
218 |
introduced |
introduce |
Present tense is better |
|
219 |
summarized |
summarize |
Present tense is better |
|
227 |
rate-limiting enzymes |
rate-limiting enzyme |
Singular |
|
235-236 |
dipeptidase (DP) which towards the extracellular membrane[44]. |
dipeptidase (DP) which moves towards…. OR …migrates towards… |
Verb is missing |
|
236 |
reverted |
recycled ??? |
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|
240 |
in male production |
in male sperm (?) production (??) |
|
|
248 |
straightly, |
‘directly’ OR ‘immediately’ ? |
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252 |
seminiferous due |
seminiferous tubules ? OR ‘semen’ |
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|
256 |
treat |
treating ? OR treatment ? |
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|
257 |
demonstrated the susceptibility |
demonstrated that the susceptibility |
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|
264 |
taken from extracellular, |
taken into cells from extracellularly |
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|
265-266 |
is proved limited[54]. |
Is proved to be limited [54]. |
|
|
275 |
could against |
could protect against ?? |
Verb is missing |
|
276 |
in later stage, |
‘in later stages’, OR ‘at a later stage’ |
|
|
300-301 |
In the mice model of oligozoospermia, which were given testicular injection of 300 busulfan, |
a)In the mouse model of oligospermia, which is mice given testicular injection… OR b)In the mouse model of oligospermia, in those mice then given testicular injection… |
Do the authors mean a)that the mouse model is created by the testicular injection ? b) Do they mean that the testicular injection was given to the already-existing mouse model ? This needs clarifying as suggested. |
|
307-308 |
when considering ferroptosis as a treatment for male infertility, |
when considering inhibition of ferroptosis as a treatment…. |
do the authors mean ferroptosis; or do they mean inhibition of ferroptosis as the treatment ? |
|
315-318 |
Phospholipid hydroperoxides… …disorders and ferroptosis |
|
This sentence is too complex in structure, and very difficult to find its sense. Please re-write. |
|
320-323 |
When the capacity…will be provoked |
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This sentence is also too complex in structure, and very difficult to find its sense. Please re-write. |
|
323 |
It can occur by both non-enzymatic driven |
This can occur by both non-enzymatic means (OR ‘processes’ ?) driven…. |
|
|
342 |
whose derivatives attach importance |
whose derivatives are of importance |
|
|
358 |
different those |
different from those |
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|
362 |
structure altered, it |
structure is altered, it… |
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|
363 |
negatively affects their |
negatively affecting their |
|
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364 |
sperms are lack of related |
sperms have a lack of related OR sperms are lacking related |
|
|
375 |
shown that it exists PUFA incorporation into |
shown the existence (OR occurrence ?) of PUFA incorporation into… |
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|
383 |
currently identified ferroptosis occurred in male |
….ferroptosis occurring in the male… |
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|
402 |
by-product lipid peroxide |
by-products of lipid…. |
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408 |
thus resulting diseases in male |
thus resulting in diseases of the male…. |
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|
414-415 |
preventing lipid peroxidation process or running out of LIP as targets for treatment intervention point of ferroptosis, may be of potential value treating |
preventing the lipid peroxidation process, or running…..targets for any treatment-intervention-point in ferroptosis, may be of potential value in treating…. |
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|
425-426 |
Whether the different sensitivity to ferroptosis of different cells during spermatogenesis is one of the |
Is the different sensitivity… …spermatogenesis one of the…. |
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428 |
Relative research |
‘Relevant research’ OR ‘Related research’ |
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430-431 |
There may exists a vast untapped terrain of ferroptosis which has a broad potentially prospect. |
|
Unfortunately this sentence does not make any sense. Please re-write. |
Comments for author File: 
Comments.pdf
Author Response
Please see the attachment.
Author Response File: 
Author Response.docx
Reviewer 2 Report
The authors reviewed a novel type of cell death in male reproduction; however, the following questions should be clarified before decision:
Minor revisions
1. It would be good if you could write the type of current study (e.g. experimental study, etc.) in the both abstract and materials & methods sections.
2. Write the abbreviation of all words where they are mentioned for the first time within the manuscript (abstract & text body).
Major revisions
1. Figure 1 is not mechanistic. Please complete this figure using more mechanistic pathways.
2. It would be well if you could show the process of papers’ selection, selection criteria by which you have chosen articles for the study.
3. Creating tables summarizing experimental studies and results for each section is mandatory. In another word, you could make a table for each pathophysiology in which studies and the outcomes are summarized.
4. Creating some figures to show mechanisms of each pathophysiology would be great.
5. English editing of the manuscript is necessary.
Author Response
Please see the attachment.
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
Ferroptosis Re-review report Dec 2022
(this re-review report is also attached as a PDF file to ensure the original Word file formatting is retained)
The authors have attended satisfactorily to the corrections which I suggested in my original review, although some of the additional re-written passages do need further attention to the English, as indicated below. However, in noting also the comments of Reviewer 2 on the original version, I would agree that, as a literature review, the authors do need to explain in this paper, rather than just in their cover note, what their method of approach to researching the literature.
Points
1. The above would seem best achieved by adding a ‘Materials & Methods section’ between Section 1 (Introduction) and Section 2 (The discovery of ferroptosis). Alternatively if the authors prefer to do this as Supplementary Material, but at the least, referred to by inserting a suitable heading between section 1 & 2, that would seem acceptable.
2. In addition to the overall list of abbreviations, each of the Figures would benefit from having some information as a Legend, not just the title of the Figure. In particular this should include a guide to at least some of the abbreviations used in the Figure, particularly where these may be less familiar, as a Figure is much easier to follow where that information is immediately available attached to it.
3. The overall list of abbreviations would work better for the reader if they were listed in alphabetical order (by abbreviation) rather than in order of first appearance in the text.
4. Multiple Corrections to the English (or removal of ambiguity) are again required, particularly in the re-written text, but also some in the ‘auto-polished’ text. These are (* The Line number refers to the supplied pdf version which includes the 3 different coloured types of mark-up) :
|
Line* |
Present text |
Suggested revised text |
Comment |
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17 |
In this review |
In this literature-based review |
To amplify reviewer 2’s comment re defining the type of study. |
|
19 |
abnormal upon iron metabolism |
Delete ‘upon’ |
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146-148 |
It is worth noting….. |
Delete one copy of this sentence |
Sentence has been duplicated |
|
161 |
Sertoli cells store the acquired iron in ferritin, which would be secreted and return to primary spermatocytes. |
Should the word be 'returned': ie. that the iron is returned to the primary spermatocytes ? |
This could currently read that the Sertoli cells would return to (being) primary spermatocytes, or return to be adjacent to primary spermatocytes. |
|
204 |
F.Sun et al |
?? Zhao et al |
Is this reference 33, or is there a paper of Sun et al that needs citing as a separate reference ? |
|
240 |
pf |
of |
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269 |
ferroptosis in male productive system |
ferroptosis in the male reproductive system |
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325 |
sperms |
sperm |
See comment below against lines 395-8 |
|
348 |
And the process… |
The process… |
Sentences cannot start with ‘And’. |
|
395-8 |
Sperm has high content of….which are different from those…., so it is not….conclude that they are more vulnerable…. |
Sperm have a high content of….. [then one of:] which are different ones from those…., so it is not…conclude that the sperm are more vulnerable….
which is a different situation from somatic cells, so it is not…conclude that the sperm are more vulnerable….
|
The term ‘sperm’ (like the term ‘sheep’) covers both singular and plural. Also, it is currently ambiguous whether the authors mean that having a high content of PUFA in sperm is a different situation from somatic cells; or whether the types of PUFA in sperm are different from those in somatic cells. |
|
402-4
407 |
Moreover, sperm has a lack… ….it is unable…. |
[Either:] Moreover, a sperm has a lack… …it is unable… …
|
See above |
|
421 |
sperms |
sperm |
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444 |
sperms |
sperm |
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464 |
sperms |
sperm |
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|
464 |
…to evaluate the male reproduction. |
…to evaluate male reproduction. |
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|
465 |
…in male reproductive system.. |
…in the male reproductive system… |
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|
466 |
Here, we summarized… |
Here, we have summarized… |
|
|
467 |
…factors from... |
…factors, classed as… [OR]…factors, grouped as… [rather than ‘factors from’] |
|
|
468 |
In human,… |
[Either:] In the human,… [OR:] In humans, … |
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|
474 |
…in microscopic level… |
…at microscopic level… |
|
|
475 |
…broken or disappeared mitochondrial ridge… |
[Either:] '...a broken or lost mitochondrial ridge...' '...a broken mitochondrial ridge, or its disappearance...'
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|
477 |
Increased density membrane |
Increased membrane density [OR:] |
|
|
479 |
…other forms of death |
…other forms of cell death |
|
|
485 |
…can be almost detected |
…can often be detected ?? |
What do the authors mean here by 'almost'? - either they are detected or they are not.
|
|
488 |
And SOD content is found… |
Also, SOD content is found.. |
Sentences cannot start with ‘And’. |
|
499-501 |
…the exposure of…
…can elicit mouse testes ferroptotic response through… |
…exposure to…
[Either:] …can elicit the ferroptotic response in mouse testes through
|
It is ambiguous here whether the authors are still referring to human testes exposed to…. which show a response similar to ferroptosis in mouse testes; |
|
515 |
The question that we raise are… |
The questions that we raise are… |
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538-581 |
Abbreviations |
Please list in alphabetical order |
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Comments for author File: Comments.pdf
Author Response
Please see the attachment.
Author Response File: Author Response.docx
Reviewer 2 Report
This manuscript has been revised accordingly. It is now acceptable.
Author Response
Please see the attachment.
Author Response File: Author Response.docx
