PONE-D-19-32025

Prenatal growth-restriction and sex influence fetal adipose tissue phenotype and impact postnatal lipid metabolism and adiposity until adulthood.

PLOS ONE

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3. According to our submissions guidelines, titles should be specific, descriptive, and concise; in this case, we suggest that your title is modified to clarify that all experiments were carried in vivo, and to specify the animal model used.

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: No

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: This study provides a robust and highly controlled model of prenatal growth-restriction obtained by maternal overnutrition to decipher the effects on adipose tissue development and selected gene expression with consequences for lipid metabolism and body composition. Rather than reporting a snapshot at a single age, serial measures across the life-course are provided. Most factors are kept constant in the adolescent sheep model (one sire, transfer of single high-quality embryos harvested from donors with a known nutritional and reproductive background into young primiparous adolescent recipients of equivalent age, weight and adiposity at conception), allowing the effects of prenatal nutrient supply and also of sex to be demonstrated.

Minor comments:

- species should be indicated in the abstract and title (ewes)

- it’s a pity that fetus-derived DLK1 expression was not include in the list of genes studied by qPCR (e.g., Nat Genet. 2016 Dec;48(12):1473-1480. doi: 10.1038/ng.3699.)

- the authors claimed for data availability. However, in the main text, means and standard errors are provided, but individual data are not included in supplementary files or repository.

Reviewer #2: This paper contributes new findings in a field that is well-known for authors. Excellent discussion and results of fetal gene expression are very interesting. Authors propose future lines of work, including more tissues and time points. I encourage them to follow them. However, some parts could be improved to increase its readability simplifying the manuscript and focusing on main ideas.

The abstract has too much information in some sentences. I think focusing on key ideas in the abstract would improve its readability. Adding ‘ovine model’ would also be better.

Good and informative introduction. However, its last parts about authors’ models and a very long and detailed second goal remember Materials & Methods.

M&M is a detailed section, but weighty. Using supplementary documents could be useful to increase readability. I also think it would be better to have diets in supplementary data than in another paper.

I think using bold type in tables is a great idea. In Results, there are averages from Experiment 2 without SEM values.

Further details:

Some keywords are also in the title.

In table 2, the meaning of symbols (*,ɤ, ß) within individual groups is difficult to understand only reading the table.

In table 3, letter b is in all the groups in PPAR, and I think restricted males should be a. The restricted female group has the highest value for UCP1, are you checking individual values looking for outliers?

L687-8: Close brackets

L727: APGAR is not previously defined

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Reviewer #1: No

Reviewer #2: No

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Ovine prenatal growth-restriction and sex influence fetal adipose tissue phenotype and impact postnatal lipid metabolism and adiposity in vivo from birth until adulthood.

PONE-D-19-32025R1

Dear Dr. Wallace,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Cristina Óvilo, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: