Related Experiment Video
Updated: Jan 10, 2026
04:08
Mouse Model of Surgical Uterine Injury and Subsequent Pregnancy Outcomes
Published on: June 27, 2025
1.0K
Endometrial Injury and Its Rescue by Mesenchymal Stem Cells Is Dependent on Estrous Cycle Phase
Ramanaiah Mamillapalli1, Ying Liu1, Yuping Zhou1
1Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA.
Journal of Cellular and Molecular Medicine
|November 26, 2025
Summary
Asherman Syndrome (AS) infertility caused by endometrial injury during the diestrus phase can be restored by bone marrow-derived mesenchymal stem cells (BM-MSCs). Treatment primarily works through immunomodulation, not cell engraftment, restoring uterine function.
Area of Science:
- Reproductive biology
- Stem cell therapy
- Gynecology
Background:
- Asherman Syndrome (AS) involves uterine scarring and infertility, often after surgical curettage, with limited surgical treatment success.
- Bone marrow-derived mesenchymal stem cells (MSCs) show promise for restoring uterine function in AS.
- The impact of the estrous cycle phase on endometrial injury and MSC treatment outcomes is unknown.
Purpose of the Study:
- To investigate the differential effects of endometrial injury during estrus versus diestrus on fertility in a murine model.
- To evaluate the efficacy of bone marrow (BM)-derived MSC treatment in restoring fertility after endometrial injury.
- To elucidate the mechanism of BM-MSC action in endometrial repair, focusing on engraftment versus immunomodulation.
Main Methods:
- Induction of endometrial injury during specific estrous cycle phases (estrus or diestrus) in mice.
- Assessment of fertility outcomes following injury and/or BM-MSC treatment.
- Immunofluorescence analysis to detect BM-MSC engraftment (vimentin, cytokeratin).
- Analysis of immune cell infiltration (CD45+) and gene expression (Ccl3, Il-1β, Mmp3) via qRT-PCR.
Main Results:
- Endometrial injury during estrus did not impact fertility, while injury during diestrus led to infertility.
- BM-MSC treatment following diestrus-phase injury restored fertility.
- BM-MSC treatment did not result in significant engraftment but increased CD45+ immune cells in the uterus.
- Gene expression analysis revealed increased Ccl3, Il-1β, and Mmp3 in the injury + BM-MSC group, suggesting an immunomodulatory mechanism.
Conclusions:
- Endometrial injury during the diestrus phase is a critical factor in AS-related infertility.
- BM-MSC therapy effectively restores fertility after diestrus-phase endometrial injury.
- The therapeutic effects of BM-MSCs in this model are primarily mediated by immunomodulation rather than direct cellular engraftment.
Related Concept Videos
01:18Menses Phase
970
The uterine cycle begins with the menstrual phase, which is considered day one of the cycle and typically lasts about five days. This phase is characterized by the degeneration and shedding of the stratum functionalis, the functional layer of the endometrium.
When fertilization does not occur, the corpus luteum deteriorates, causing a significant drop in the levels of estrogen and progesterone in the body. This hormonal decrease triggers the release of prostaglandins, which cause the uterine...
When fertilization does not occur, the corpus luteum deteriorates, causing a significant drop in the levels of estrogen and progesterone in the body. This hormonal decrease triggers the release of prostaglandins, which cause the uterine...
970
01:19Mesenchymal Stem Cells
5.5K
Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
5.5K
01:20Proliferative Phase
1.2K
The proliferative phase typically occurs after menstruation and lasts between 6 to 13 days in a standard 28-day cycle. This phase involves the reconstruction of the endometrium, guided by estrogen produced by the developing ovarian follicle.
Notably, the stratum basale, the basal layer of the endometrium, including the basal parts of the uterine glands, remains unaffected by menstruation. Stem cells in this layer undergo mitosis, regenerating the stratum functionalis and thickening the...
Notably, the stratum basale, the basal layer of the endometrium, including the basal parts of the uterine glands, remains unaffected by menstruation. Stem cells in this layer undergo mitosis, regenerating the stratum functionalis and thickening the...
1.2K
01:19The Menstrual Cycle
3.0K
The menstrual cycle is a recurrent sequence of changes in the uterine endometrium, specifically its functional layer, the stratum functionalis. This cycle prepares the uterus for potential pregnancy. This cycle typically spans 21–35 days, averaging 28 days, and aligns with the ovarian cycle, regulated by fluctuating levels of ovarian hormones, primarily estrogen and progesterone.
The menstrual phase occurs from days 1 to 5 and involves the shedding of the stratum functionalis, as a...
The menstrual phase occurs from days 1 to 5 and involves the shedding of the stratum functionalis, as a...
3.0K
01:27Ovarian Cycle
3.3K
The menstrual cycle includes a critical component known as the ovarian cycle, which undergoes two main phases each month—the follicular phase and the luteal phase. The follicular phase is variable and averaging around 14 days. Ovulation, triggered by a surge in luteinizing hormone (LH), marks the transition between the two phases. The second phase, the luteal phase, is relatively consistent, lasting approximately 14 days, and is marked by the activity of the corpus luteum. While a cycle...
3.3K
01:22Hormonal Regulation of the Menstrual Cycle
1.4K
The ovarian cycle regulates endometrial changes throughout a single menstrual cycle via the coordinated action of gonadotrophin-releasing hormone (GnRH) and gonadotrophins.
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...
1.4K