Related Experiment Video
Updated: Jul 18, 2026
Exploring Independent Effects of Follicle-Stimulating Hormone In Vivo in a Mouse Model
Published on: August 11, 2023
Ovarian wedge resection restores fertility in estrogen receptor beta knockout (ERbeta-/-) mice
José Inzunza1, Andrea Morani, Guojun Cheng
1Division of Medical Nutrition, Department of Biosciences and Nutrition, Karolinska University Hospital, Karolinska Institutet, NOVUM, S-141 86 Stockholm, Sweden.
Abstract:
Ovulation rarely occurs in mice in which the estrogen receptor beta (ERbeta) gene has been inactivated (ERbeta-/- mice). Here, we investigated whether this subfertility is due to a defect in the ovary itself or to more general endocrine changes in ERbeta-/- mice. We transplanted ERbeta-/- ovaries into WT mice and WT ovaries into ERbeta-/- mice. Upon mating with ERbeta-/- males, fertility increased from 20% in control intact ERbeta-/- group to 40% in the WT recipients with ERbeta-/- ovaries. The transplantation procedure was not efficient, and when WT ovaries were transplanted into WT mice, fertility was only 36%. Surgical ovarian wedge resection, a procedure which induces ovulation in anovulatory women with polycystic ovarian syndrome, resulted in 100% fertility of ERbeta-/- mice. In ERbeta-/- mice, as the follicles enlarged, the thecal layer remained very compact (revealed by H&E and collagen staining), and there was no increase in vascularization (measured as smooth muscle actin). In addition, there was an increase in PDGF receptor alpha (PDGFRalpha) and a decrease in PDGFbeta expression in the granulosa cells, similar to what has been found in follitropin receptor knockout mice. After wedge resection, expression of both smooth muscle actin and PDGFRs was normalized. During normal follicular development, increased vascularization of the thecal layer is a prerequisite for further follicular growth. We suggest that the defect in ERbeta-/- mouse ovaries is a failure of communication between the granulosa and thecal layers. The follicles do not mature because of insufficient blood supply. This problem is overcome by stimulating neovascularization by simple wedge resection of the ovaries.
Insights
Estrogen receptor beta (ERbeta) deficiency causes infertility in mice due to poor ovarian vascularization. Ovarian wedge resection restored fertility by promoting blood supply and follicle maturation.
Area of Science:
- Reproductive Biology
- Endocrinology
- Molecular Biology
Background:
- Estrogen receptor beta (ERbeta) plays a crucial role in female reproduction.
- ERbeta knockout (ERbeta-/-) mice exhibit significantly reduced ovulation and subfertility.
- The underlying cause of subfertility in ERbeta-/- mice remains unclear, with possibilities including ovarian defects or systemic endocrine changes.
Purpose of the Study:
- To determine if subfertility in ERbeta-/- mice stems from intrinsic ovarian defects or broader endocrine alterations.
- To investigate the impact of ovarian wedge resection on fertility in ERbeta-/- mice.
- To elucidate the role of vascularization and growth factor signaling in ERbeta-/- ovarian dysfunction.
Main Methods:
- Ovarian transplantation experiments: ERbeta-/- ovaries into WT mice and WT ovaries into ERbeta-/- mice.
- Surgical ovarian wedge resection in ERbeta-/- mice.
- Histological analysis (H&E, collagen staining) and immunohistochemistry (smooth muscle actin, PDGFRalpha, PDGFbeta) to assess ovarian structure and vascularization.
- Fertility assessments through mating trials.
Main Results:
- Ovarian transplantation partially restored fertility in ERbeta-/- mice, suggesting an ovarian component to subfertility.
- Surgical ovarian wedge resection normalized fertility in ERbeta-/- mice, achieving 100% success.
- ERbeta-/- ovaries showed impaired thecal layer vascularization and altered PDGF receptor expression in granulosa cells.
- Wedge resection normalized vascularization and PDGF receptor signaling in ERbeta-/- ovaries.
Conclusions:
- The subfertility in ERbeta-/- mice is primarily due to an intrinsic ovarian defect characterized by insufficient vascularization of the thecal layer.
- This vascular defect impairs communication between granulosa and thecal cells, hindering follicular maturation.
- Ovarian wedge resection effectively overcomes this defect by stimulating neovascularization, restoring fertility.
