Menstruating Mice?!: A Gateway to Advancing the Study of Human Reproductive Physiology
- jayashree ganesan
- Nov 20, 2025
- 3 min read
Yes. You read that right. Scientists in Dr. McKinley's lab at Harvard's Department of Stem Cell and Regenerative Medicine have now developed transgenic mice models that marks a new beginning in understanding human reproductive physiology.
Why is this impressive?
For starters, menstrual research is an area that has been minimally investigated in the past for a couple of reasons.
The overall lack of emphasis on biological women's health and research due to social stigma and limited funding.
Common lab rodents like mice do not naturally menstruate. This meant we did not possess the means to study it using animal models.
Hence, their effort enables researchers studying reproductive biology to gain insights into the science of menstruation. This also facilitates the scientific understanding of uterine diseases like endometriosis and adenomyosis.
The Science of Inducing Menstruation in Female Mice
The reason biomedical researchers mostly use mice models for studying physiology and disease is the similarities between humans and mice, in terms of anatomical and physiological characteristics.
There are some key concepts that are involved in creating these mice.
DREADD receptors & Chemogenetics
G-protein coupled receptors called DREADDs aka Designer Receptors Exclusively Activated by Designer Drugs were bioengineered into the endometrium (or uterine wall, that is eventually shed through menstruation). This allows for selective activation of cell signaling pathways by certain substances (agonists).[1]
In their study, Dr. McKinley's lab has created 2 separate strains of transgenic mice (X-mens) that express different DREADD agonists. [1]
A key feature in human menstrual cycles is DECIDUALIZATION: a process through which fibroblasts in the endometrium transform in order to prepare the uterus for pregnancy.[1] Controlled by progesterone levels, this occurs post ovulation, when there is a rise in progesterone levels. During cycles (w/o pregnancy), progesterone levels drop and causes the decidualized tissue to degrade and menstruation occurs.[1]
In mice, however, decidualization only occurs upon implantation of the embryo. [1] This is why they do not undergo menstruation. Certain studies have indicated that decidualization can be induced via administering vegetable oil in the uterine lumen during normal cycles without pregnancy. [1]
The development of these transgenic, menstruating mice has been achieved by targeting cAMP signaling in endometrial fibroblasts & increase in calcium levels in the endometrial epithelium. [1]
The abovementioned cell signaling pathways play a crucial role in mice decidualization, making them a core aspect to furthering our understanding of menstruation and uterine health. [1]
Pseudopregnancy & Injection Administration
Female mice were set up to breed with males that underwent vasectomies. Once a vaginal plug was observed, they were separated and observed. These females then received intraperitonial injections containing DREADD agonists. [1]
Subcutaneous administration of Mifepristone (a progesterone antagonist (a substance that has an inhibitory effect)) was conducted in one strain of X-Mens after 2 days from the DREADD injections to rule out any change in menstruation due to progesterone levels. [1] Post these injections, mice menstruated within a day. This set out to point out that menstruation in these mice occurred due to the decrease in progesterone, just like humans. [1]
Molecular Biology to Analyze the Endometrium ...
- Decidualization was confirmed through the levels of prolactin gene expression (Prl8a2) via qPCR (quantitative PCR) [1]
- Histological staining (Hematoxylin & Eosin) & Immunofluorescence: used to visualize & analyze harvested uteri of the mice [1]
- Organoid modeling from "menstrual effluent" [1]
- sc-RNA seq (single cell RNA sequencing) results to provide insights into the organization of decidual cells. [1]
- spatial mapping techniques help point out the subtypes of decidual cells and their locations.[1]
Applications & Future Directions
As mentioned earlier, the development of these mice models provide scientists the means to advance how we view and understand menstruation. Holding immense potential to transform scientific notions around menstruation and uterine health, it definitely proves to be a valuable model to investigate reproductive physiology.
References
Preprint of the article: https://doi.org/10.1101/2025.10.08.681007
TOI news article:
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