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Effect of tamoxifen on ovarian reserve: A randomized controlled assessor-blind trial in a mouse model
Ayşe Topçu Akduman1, Kemal Özerkan1, Berrin Zik2
1Department of Obstetrics and Gynecology, Uludağ University Faculty of Medicine, Bursa, Turkey.
Objective:
To determine whether tamoxifen (TMX) exposure causes a permanent decrease in ovarian reserve.
Material And Methods:
A randomized controlled assessor-blind trial including 30 adult female inbred BALB/C mice. Fifteen mice in the TMX group were given a single 0.1-mg dose of TMX intraperitoneally. Fifteen mice in the control group were given a single dose of the vehicle at the same volume intraperitoneally. Two cycles later, blood samples were collected for determination of anti-Müllerian hormone (AMH) levels, and the mice were sacrificed. After gonadectomy, ovarian size was measured, and follicles were counted under light microscopy.
Results:
Median serum AMH levels were 6.53 and 6.14 ng/ml in the control and TMX groups, respectively (p=0.03). Ovarian size was significantly decreased in the TMX group. While the number of primordial (9 vs 8), primary (6 vs 3), and secondary (4.5 vs 5) follicles were similar, there were significantly fewer preantral (11.5 vs 6, p<0.01) and antral (2 vs 1, p: 0.03) follicles, as well as corpora lutea (6 vs 3, p: 0.04), in the TMX group than in the control group. The number of atretic (2.5 vs 5, p: 0.048) follicles was increased in the TMX group.
Conclusion:
Tamoxifen administration leads to arrested growth of gonadotropin-sensitive follicles, while insensitive follicles can remain unaffected. TMX is merely an endocrine disruptor, and it does not cause a decrease in primordial follicle pool.
Insights
Tamoxifen (TMX) exposure in mice did not permanently decrease the primordial follicle pool, but it did reduce ovarian size and the number of developing follicles. This suggests TMX acts as an endocrine disruptor affecting follicle growth.
Area of Science:
- Reproductive biology and endocrinology.
- Toxicology and pharmacology.
Background:
- Tamoxifen (TMX) is a widely used medication with known endocrine-disrupting properties.
- The impact of TMX on ovarian reserve and long-term fertility remains a critical area of investigation.
Purpose of the Study:
- To investigate the potential for tamoxifen exposure to induce a permanent reduction in ovarian reserve in a murine model.
- To assess the effects of tamoxifen on ovarian size, follicle counts, and anti-Müllerian hormone (AMH) levels.
Main Methods:
- A randomized controlled trial was conducted on 30 female BALB/C mice.
- Mice received either a single dose of tamoxifen (TMX) or a vehicle control.
- Ovarian reserve was assessed by measuring serum AMH levels, ovarian size, and follicle counts (primordial, primary, secondary, preantral, antral, atretic) and corpora lutea post-sacrifice.
Main Results:
- Tamoxifen administration resulted in significantly decreased ovarian size and fewer preantral and antral follicles compared to controls.
- Serum AMH levels were slightly reduced in the TMX group (p=0.03).
- The number of atretic follicles increased, while the primordial follicle pool remained unaffected.
Conclusions:
- Tamoxifen acts as an endocrine disruptor, primarily by arresting the growth of gonadotropin-sensitive follicles.
- TMX exposure does not appear to cause a permanent depletion of the primordial follicle pool.
- Further research is needed to fully elucidate the long-term reproductive consequences of tamoxifen exposure.
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