Abstract
Menstruation, the cyclical breakdown of the uterine lining, is arguably one of evolution's most mysterious reproductive strategies. The complexity and rarity of menstruation within the animal kingdom is undoubtedly a leading contributor to our current lack of understanding about menstrual function and disorders. In particular, the molecular and environmental mechanisms that drive menstrual and fertility dysregulation remain ambiguous, owing to the restricted opportunities to study menstruation and model menstrual disorders in species outside the primates. The recent discovery of naturally occurring menstruation in the Egyptian spiny mouse (Acomys cahirinus) offers a new laboratory model with significant benefits for prospective research in women's health. This review summarises current knowledge of spiny mouse menstruation, with an emphasis on spiral artery formation, inflammation and endocrinology. We offer a new perspective on cycle variation in menstrual bleeding between individual animals, and propose that this is indicative of fertility success. We discuss how we can harness our knowledge of the unique physiology of the spiny mouse to better understand vascular remodelling and its implications for successful implantation, placentation, and foetal development. Our research suggests that the spiny mouse has the potential as a translational research model to bridge the gap between bench to bedside and provide improved reproductive health outcomes for women.
Highlights
The menstrual cycle is a process in which the uterine lining sheds, regenerates, and terminally differentiates in preparation for pregnancy
Similarities were evident in the uterine secretion of inflammatory and repair markers interleukin-8 and macrophage inhibitory factors, as well as the localised focal shedding and adjacent repair of the endometrium [11]. These studies demonstrated behavioural and physiological similarities between spiny mice and other naturally menstruating species, in that changes in food consumption, weight fluctuations, anxiety, and exploration are driven by menstrual cycle stage and suggestive of a human-like premenstrual syndrome (PMS) [12]
The question remains: what are these benefits? Having observed such a large natural variation of bleeding in a species which has not been subjected to selective pressures of environment and predation, we hypothesise that females with heavy menstrual bleeding have a selective advantage for breeding. Their vessels undergo more extensive remodelling, resulting in optimal placental nutrient and gas exchange and, larger and/or more offspring can be supported.: The subsequent excessive blood loss during menstruation stems from increased spiral artery formation and a thicker endometrial lining, both of which are stimulated by the androgen DHEA
Summary
The menstrual cycle is a process in which the uterine lining sheds, regenerates, and terminally differentiates in preparation for pregnancy. Similarities were evident in the uterine secretion of inflammatory and repair markers interleukin-8 and macrophage inhibitory factors, as well as the localised focal shedding and adjacent repair of the endometrium [11] These studies demonstrated behavioural and physiological similarities between spiny mice and other naturally menstruating species, in that changes in food consumption, weight fluctuations, anxiety, and exploration are driven by menstrual cycle stage and suggestive of a human-like premenstrual syndrome (PMS) [12]. Having observed such a large natural variation of bleeding in a species which has not been subjected to selective pressures of environment and predation, we hypothesise that females with heavy menstrual bleeding have a selective advantage for breeding Their vessels undergo more extensive remodelling, resulting in optimal placental nutrient and gas exchange and, larger and/or more offspring can be supported.: The subsequent excessive blood loss during menstruation stems from increased spiral artery formation and a thicker endometrial lining, both of which are stimulated by the androgen DHEA. The spiny mouse may provide fundamental preclinical data on long-term menstrual physiology and associated birth outcomes, enabling identification of new biomarkers and aid in developing surveillance protocols for at-risk females
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