The Role of Immunologic Factors in Endometrial Receptivity: An Embryo–Endometrium Dialogue

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The unique immune environment in the maternal-fetal interface is an attractive field for reproduction, immunology, and biomedical studies. In this manuscript, the authors provide a comprehensive, well‑structured review on the immune regulation in the maternal-fetal interface. Apart from describing uterine-resident immune cells such as uNKs, Tregs, NKs, and macrophages, this manuscript also properly covers relevant signaling molecules, key signaling pathways, embryo-endometrium dialogues, as well as potential clinical translation. Overall, the manuscript is interesting and scientifically sound, and is expected to be attractive for researchers studying reproduction and immunology.

Below I have a few comments for further improvement:

1. The topic of this manuscript belongs to an attractive and growing field. While this manuscript is well-structed and successfully covers many previous papers, the current list of 46 citations is a little bit short. The authors are encouraged to include more citations is possible.
2. Lines 56-60: the commas should be placed outside of the quotation marks.
3. Line 73: “CD56^bright^CD16^−^” appears as a typo. It should be presented correctly.
4. Figure 1: the title at the top of this figure is redundant and should be removed; on the right side, the font size of macrophage is too big and should be adjusted to the same size of uNK and other cell types. in its legend, repeated definitions of the abbreviations (e.g., hCG, EV, uNK) should be avoided.
5. Line 9390: author contributions should be provided.
6. Lines 403-440: singular form is preferable for the abbreviations.

Author Response

The authors of the current study want to thank very much the expert Reviewer-1 for all valuable comments and suggestions. 

Comment 1: The topic of this manuscript belongs to an attractive and growing field. While this manuscript is well-structed and successfully covers many previous papers, the current list of 46 citations is a little bit short. The authors are encouraged to include more citations is possible.

Response 1: Thank you for this comment. We have, accordingly, included more citations which you can be found in lines 469-470, 474, 482-483, 487, 490-491, 499-500, 501-502, 516-517.

Comment 2: Lines 56-60: the commas should be placed outside of the quotation marks.

Response 2: Thank you for pointing this out. Therefore, we have corrected that (Lines 56-60).

Comment 3: Line 73: “CD56^bright^CD16^−^” appears as a typo. It should be presented correctly.

Response 3: Thank you for pointing this out. We have, accordingly, replaced it with the correct form (Line 74).

Comment 4: Figure 1: the title at the top of this figure is redundant and should be removed; on the right side, the font size of macrophage is too big and should be adjusted to the same size of uNK and other cell types. in its legend, repeated definitions of the abbreviations (e.g., hCG, EV, uNK) should be avoided.

Response 4: Thank you for this comment. We have, accordingly, modified the figure (Line 284). We have also removed the title of this figure and the definitions of the abbreviations (Lines 285 – 292).

Comment 5: Line : author contributions should be provided.

Response 5: Thank you for pointing this out. We have completed all the authors’ contributions (Lines 400   – 402  ).

Comments 6: Lines 403-440: singular form is preferable for the abbreviations.

Response 6: We agree with this comment. Therefore, we have used singular form for all the abbreviations (Lines 413 – 451).

Reviewer 2 Report

Comments and Suggestions for Authors

The article is very relevant and well prepared.
It is necessary to add some more practical recommendations to the subsections.
For example, when writing about inflammation or oxidative stress, mention whether it would be appropriate to prescribe antioxidants to achieve greater implantation success.

Author Response

Comment: The article is very relevant and well prepared.
It is necessary to add some more practical recommendations to the subsections.
For example, when writing about inflammation or oxidative stress, mention whether it would be appropriate to prescribe antioxidants to achieve greater implantation success.

Response: The authors of the current study want to thank very much the expert Reviewer-2 for his valuable comment. In the current version of the manuscript we have added some therapeutic options offered to women with recurrent implantation failure due to oxidative stress or due to altered immunological profile. Since these treatments are not generalized accepted we preferred not to analyse extensively these therapeutic approaches. Therefore, in the section 6 of the manuscript lines: 312-320 we have added some promising therapeutic modalities.