Dysregulation of Oxygen Sensing/Response Pathways in Pregnancies Complicated by Idiopathic Intrauterine Growth Restriction and Early-Onset Preeclampsia

Round 1

Reviewer 1 Report

The paper entitled "Dysregulation of oxygen sensing/response pathways in pregnancies complicated by idiopathic intrauterine growth restriction and early-onset preeclampsia" investigates a central molecular aspect of two serious complications that can arise during pregnancy. For this reason, the the authors' work has a great clinical relevance and, moreover, the experiments are very well conducted. 

The authors could express the limitations of the study in the "Discussion section" and add more comments from a clinical point of view to the data obtained. 

Author Response

Comments and Suggestions for Authors

The paper entitled "Dysregulation of oxygen sensing/response pathways in pregnancies complicated by idiopathic intrauterine growth restriction and early-onset preeclampsia" investigates a central molecular aspect of two serious complications that can arise during pregnancy. For this reason, the the authors' work has a great clinical relevance and, moreover, the experiments are very well conducted. 

The authors could express the limitations of the study in the "Discussion section" and add more comments from a clinical point of view to the data obtained. 

The clinical significance of this study is that understanding DJ1/VHL interactions may lead to the development of therapies for both IUGR and PE.  This has been added in the discussion at line 326

……..Further research is required to fully understand these interactions and determine whether clinically, this interaction is a potential target for the development of a therapy for PE and or IUGR.

A limitation of this study is that since the placentae of PE patients have not been phenotyped they cannot be analysed in distinct groups.  Again this has been added in the discussion at line 348.

…..in individual cases or distinct phenotypes. Although sufficient pathological placentae were utilised to assess HIF regulation, a limitation of our study is that the placental tissue was not phenotyped, thus distinct sub-groups were not identified.

Reviewer 2 Report

The article is well-written, interesting and susceptible for publication.

Unfortunately, there are some minor limitations:

There are some typographical errors (for example: "PET" in the caption of Figure 1). Please explain “FIH” in the main text as well. Please use selected abbreviations (for example: “HIF-1α or HIF1α; vHL or VHL) in all parts of your article consequently.

The authors informed (in “4.1. Subjects”) that: “All SPT presented with pre-term premature rupture of membranes (PPROM) and were delivered by caesarean section (CS) …”. However, there is also a piece of information (Table 1) that “delivery by CS” was 12 (i.e. 92%) in the SPT group. Please check this data.

Please change the name “NORMAL” for the “SPT” group in Table 1 (as well as in its caption). Spontaneous pre-term deliveries are not NORMAL deliveries.

Please use "Instruction for Authors" for all references.

Author Response

There are some typographical errors (for example: "PET" in the caption of Figure 1).

PET has been changed to PE in the figure legend for Figure 1

Please explain “FIH” in the main text as well.

Full name for FIH – Factor Inhibiting HIF has been included

Please use selected abbreviations (for example: “HIF-1α or HIF1α; vHL or VHL) in all parts of your article consequently.

Both HIF and VHL abbreviations have been altered accordingly.

The authors informed (in “4.1. Subjects”) that: “All SPT presented with pre-term premature rupture of membranes (PPROM) and were delivered by caesarean section (CS) …”. However, there is also a piece of information (Table 1) that “delivery by CS” was 12 (i.e. 92%) in the SPT group. Please check this data.

Thank you for pointing this out.  We have altered this in the text to indicate one SPT was delivered vaginally, and the rest were delivered vis C-section.  This has been indicated in the section 4.1 Subjects

Please change the name “NORMAL” for the “SPT” group in Table 1 (as well as in its caption). Spontaneous pre-term deliveries are not NORMAL deliveries.

The identifier has been altered to read SPT instead of normal.

Please use "Instruction for Authors" for all references.

References in the manuscript body have been altered according to "Instructions for Authors"