How can we study menstrual physiology?
Human studies
Endometrial tissue
Women frequently undergo hysterectomy for benign conditions. These include abnormal uterine bleeding (AUB), symptomatic fibroids, and uterine prolapse.
With informed consent, patients may (anonymously) donate tissue sample surplus to routine histology for laboratory-based studies (molecular and cellular). Such uterine/ endometrial tissue may be critically examined for detailed morphological assessment, protein localization with immunohistochemistry, and RNA extracted for gene expression studies (including gene array and more sophisticated sequencing). Furthermore, endometrium may be obtained using tissue samplers allowing serial collection of tissue from the same individual at different time points thereby allowing assessment of the effects of in vivo treatments without necessitating removal of the uterus.Endometrial cells
Both epithelial and stromal cells may be extracted from endometrial tissue samples and cultured in vitro. This allows the opportunity for in vitro treatment to explore mechanism. Cells may be cultured separately or in co-culture which permits study of paracrine interactions between cell types and simulation of the in vivo environment.
Non-invasive imaging-ultrasonography, computed tomography, and magnetic resonance imaging
Imaging methods are well established in gynaecology. High- resolution transvaginal ultrasound scanning can facilitate assessment of follicle development and release as well as the study of endometrial thickness in response to circulating steroid hormones, and myometrial defects such as uterine fibroids and adenomyosis, that can cause menstrual disorders. Computed tomography is less used for the study of menstrual physiology but high-resolution magnetic resonance imaging permits non-invasive and non-ionizing assessment of the reproductive tract and the opportunity to study longitudinal changes over time.
Developing modalities of magnetic resonance imaging such as diffusion, dynamic contrast, and functional protocols assessing water content and blood flow respectively are increasing our understanding of dynamic changes in the uterus/ endometrium.Animal models
There are many ethical and practical limitations to the studies that may be conducted on humans. To obtain incisive data on menstrual physiology for onward translation to clinical management, an animal model of menstruation is necessary.
Non-human primate (rhesus macaque)
Old world primates naturally menstruate but the major contribution of this non-human primate model has been due to the ability to exclude hormonal fluctuations that naturally occur between ani- mals/women. Removal of the ovaries and sequential administration of oestradiol and progesterone mimics the human proliferative and secretory phases. Removal of progesterone initiates menstruation in a predictable fashion (35). This is attractive for experimental data collection. This uniformity of hormone exposure allows a decreased number of animals to generate equally precise experimental data, a significant advantage over human studies.
Murine model of simulated menses
A species that does not naturally menstruate is not an immediately obvious model for studies on the mechanism of menstruation. However, simulating menstruation in the mouse by removal of ovaries, sequential hormone administration, and administration of oil to the uterus to encourage decidualization, results in a process analogous to menstrual bleeding. Various refinements of this model now exist, including pseudopregnancy to decidualize the uterus (36-38). The mouse has major advantages as an experimental model: a rapid breeding time to limit costs, ready availability of laboratory reagents, and the ability to easily perform genetic modifications to enable definitive experimental outcomes. These models have confirmed and increased our knowledge of menstruation and endometrial function.