This review covers an interesting topic, relevant for the Journal of Neuroendocirnology. The focus on comparison of mouse models with early pregnancy in humans is an important one, and the review raises a number of important areas that should be considered in evaluating this sort of work.

I think it needs a bit of work to establish a consistent narrative. In some parts, it seems to be presented as a review about early placental development and miscarriage, and in others it is presented about being specifically about the role of kisspeptin in the placenta in early pregnancy. An example of this issue is the abstract, for which 90% of it is about early development and problems with mouse models, but then it ends with a statement that the review is about kisspeptin (which is not mentioned in the earlier parts of the abstract). This is not a major issue, but one which could be significantly improved by small changes throughout the manuscript. In the exmaple of the abstract, I tihnk it sohuld start with the information that the review will focus on kisspeptin, then go into the specific health question and why animal models are required, but have specific limitations. However, try to weave in how this is relevant to understanding the question of the role of kisspeptin in this process. Some of the evidence from the section started line 6364 could be introduce early on, to establish the connection between placental kisspeptin and implantation/miscarriage, and then work through the use of animal models to advance understanding.

The review does not touch on the paradox of elevated kisspeptin in blood from the placenta, but low levels of gonadotrophins at this time. Why doesn’t placental kisspeptin stimulate gonadotropin secretion? Is this because of desensitisation of the receptor? Or inhibitory dominance by high progesterone? Similarly, the review describes the kiss1 KO as a model of miscarriage (line 91-92). But kiss1 KO are infertile? How is pregnancy established in these mice? More information is required to understand this model.

I think the manuscript would benefit by a figure/diagram showing the proposed sources of kisspeptin, siters of action, and timing of events in pregnancy. For example, the review describes the placenta as a major source of kisspeptin, then later describes kiss1r in the uterus around the time of implantation. However, there would be no placental kisspeptin around the time of implantation – so what is the source of ligand at this time? Perhaps from the uterus itself? A diagram would be very helpful in interpreting all of the data discussed in the review.

Minor corrections/suggestions
Line 37: Prevalence of miscarriage
Line 64: Be explicit that you are referring to hypothalamic kisspeptin expression here.
Line 66: Please mention whether you are also talking about circulating kisspeptin (in maternal blood) in humans and mice.
Line 71: Perhaps finish this segment with a hypothesis of what kisspeptin might be doing to support early pregnancy, or a statement of our current understanding. This would flow nicely into the dicussion of animal models to advance our understanding.
Line 199: see also PMID: 24051579. This study found that rescue of the kiss1R in GnRH neurons was sufficient for normal fecundity, suggesting any role in the placenta may not be essential?
Line 208 treat to plates...wording of sentence?
Line 305: Be clear that placental lactogen is not the same as prolactin, although it acts through the prolactin receptor.
Line 325: might like to mention the necessity of a spontaneous luteal phase to enable survival of the corpus luteum until implantation occurs, as distinct from rodents with a very short luteal phase needing a mating-induced signal as a surrogate marker for pregnancy.
Line 343 – make clear that you are talking about human pregnancy where placenta makes progesterone – as distinct from rodent pregnancy where ovarian progesterone is required. This paragraph starts out being about mice, then turns into being about humans on an unrelated point.

The authors have done an excellent job in responding to the comments and the manuscript is improved. I think this is a valuable contribution to the literature on this topic. No further comments.