ABSTRACT
Background Advances in research relating to menstruation and associated disorders (such as endometriosis and pre-menstrual syndrome) have been hindered by the lack of an appropriate animal model. Thus, many aspects of this phenomenon remain poorly understood limiting the development of efficacious treatment for women. Menstruating species account for only 1.5% of mammals, and less than 0.09% of these are non-primates. Menstruation occurs as a consequence of progesterone priming of the endometrial stroma and a spontaneous decidual reaction. At the end of each infertile cycle as progesterone levels decline the uterus is unable to maintain this terminally differentiated stroma and the superficial endometrium is shed. True menstruation has never been reported in rodents.
Objective Here we describe the first observation of menstruation in a rodent, the spiny mouse (Acomys cahirinus).
Study Design Virgin female spiny mice (n=14) aged 12-16 weeks were sampled through daily vaginal lavage for 2 complete reproductive cycles in our in-house colony at Monash Medical Centre, Clayton, Australia. Stage-specific collection of reproductive tissue and plasma was used for histology, prolactin immunohistochemistry, and ELISA assay of progesterone (n=5 / stage of the menstrual cycle). Normally distributed data are reported as the mean ± standard error and significant differences calculated using a one-way ANOVA. Non-normal data are displayed as the median values of replicates (with interquartile range) and significant differences calculated using Kruskal-Wallis test.
Results Mean cycle length was 8.7 ± 0.4 days with red blood cells observed in the lavages over 3.0 ± 0.2 days. Cyclic endometrial shedding and blood in the vaginal canal concluding with each infertile cycle was confirmed in all virgin females. The endometrium was thickest during the luteal phase, when plasma progesterone peaked at ~102.1 ng/mL and the optical density for prolactin immunoreactivity was strongest. The spiny mouse undergoes spontaneous decidualisation, demonstrating for the first time menstruation in a rodent.
Conclusion The spiny mouse is the first rodent species known to menstruate and provides an unprecedented natural non-primate model to study the mechanisms of menstrual shedding and repair, and may be useful in furthering our understanding of human specific menstrual and pregnancy associated diseases.
Footnotes
The authors report no conflict of interest.
Financial Support: H.D. is an NHMRC Career Development Fellow. Part funding for this project was obtained from National Health & Medical Research Council of Australia to H.D. and a grant from the Victorian Government Infrastructure Support Fund to the Hudson Institute of Medical Research.
Paper presentation information: Society for Reproductive Investigation 63rd Annual Scientific Meeting, Montreal, Quebec, Canada, March 16–19, 2016; Perinatal Society of Australia and New Zealand, Townsville, Queensland, Australia May 22–25, 2016
Condensation: The spiny mouse represents the only known rodent to naturally menstruate, characterised by cyclical spontaneous decidualisation and endometrial shedding and repair.