This review explains that a protein called kisspeptin, made by the uterus and placenta, helps early pregnancy steps like embryo implantation, and that messing with its signals can cause infertility. Most of the evidence comes from mice, and the findings don’t always match what happens in humans, so we can’t directly apply it yet.

Hypothalamic KISS1 and its derivatives (kisspeptins) are now well recognized as potent stimulators of GnRH secretion and thereby major regulators of the neuroendocrine-reproductive axis. Recent studies in the mouse strongly suggest that independent of the hypothalamus and pituitary, peripherally derived KISS1 also regulates fertility, and disruption of local KISS1 signaling in the ovary and uterus is sufficient to trigger infertility. With this increasing recognition that peripherally derived KISS1 regulates fertility, the first goal of this review is to critically discuss the data that have led to this conclusion, focusing on uterine- and placental-derived KISS1. Given that a significant amount of this data was generated in animals such as the mouse and rat, a second goal of this review is to identify and discuss the limitations of the animal data in the context of better understanding KISS1 as a regulator of human pregnancy. The growing evidence suggests that in both man and mouse, KISS1 plays an important role in regulating very early pregnancy events such as embryo implantation. However, as pregnancy advances, although it seems that KISS1 continues to play important roles in regulating human pregnancy, it might not do so in the mouse. This surprising functional dichotomy between human females and mice appears also to exist between women and a large number of animal species, including lower primates. These findings are of tremendous significance and will greatly shape how KISS1 will be developed as a therapeutic agent in augmenting the reproductive potential of both women and important livestock species.