Tamoxifen Activates Dormant Primordial Follicles in Mouse Ovaries

Wei, Wei; Komatsu, Kouji; Osuka, Satoko; Murase, Toshiro; Bayasula, Bayasula; Nakanishi, Natsuki; Nakamura, Tomoko; Goto, Maki; Iwase, Akira; Masubuchi, Satoru; Kajiyama, Hiroaki

doi:10.1007/s43032-022-00896-0

Cited by 4 publications

(4 citation statements)

References 38 publications

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“…TAM administration in adult mice did not affect the number of primordial and primary follicles but decreased the number of growing follicles ( Akduman et al 2014 ). TAM was also shown to activate dormant primordial follicles transiently ( Wei et al 2022 ). No alteration of the follicle number or prevalence of granulosa apoptosis was found in rats ( Nynca et al 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Impaired fertility in adenomyosis: a murine model reveals endometrial receptivity and progesterone resistance imbalances

Squatrito,

Vervier,

Bindels

et al. 2024

Reproduction

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This study investigates the intricate relationship between adenomyosis and reproductive health using a murine model, offering novel insights into this prevalent gynecological disorder. Adenomyosis, characterized by the invasive growth of endometrial tissue into the myometrium, is believed to negatively impact fertility. However, the challenge lies in disentangling this influence, as adenomyosis often coexists with other gynecological diseases. A tamoxifen-induced mice model presents a significant advantage by enabling the specific study of adenomyosis, devoid of confounding influences of concurrent gynecological diseases such as endometriosis. Focusing exclusively on adenomyosis, our study aims to elucidate pathogenic mechanisms underlying fertility issues, focusing on estrous cyclicity, ovarian follicle development, and overall fertility. Our findings uncover disruptions in estrous cyclicity, characterized by an increased duration of time spent in the estrus phase in adenomyosis-induced mice. These disturbances are potentially linked to observed compromised folliculogenesis and the remarkable reduction in litter number and size in mice affected by adenomyosis. Moreover, this study unveils potential drivers of subfertility such as progesterone resistance and altered endometrial receptivity. Within the uteri of mice with adenomyosis, reduced expression of the progesterone receptor and a decreased expression of two implantation-related markers (HoxA10 and Integrin b3) were observed. This comprehensive examination sheds light on the nuanced complexities of adenomyosis-associated reproductive challenges, providing a foundation for targeted interventions in addressing fertility issues related to this disease.

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Section: Discussionmentioning

confidence: 99%

Impaired fertility in adenomyosis: a murine model reveals endometrial receptivity and progesterone resistance imbalances

Squatrito,

Vervier,

Bindels

et al. 2024

Reproduction

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“…38 In addition, recent animal studies have indicated that E2 has important roles in follicle development. 39,40 Follicle development is observed when gonadotropins are decreased during HRT. Theoretically, elevated serum luteinizing hormone levels induce premature luteinization of the antral follicles, 41 and elevated FSH levels downregulate the expression of granulosa cell FSH receptors in patients with POI.…”

Section: Hrt and Gonadotropin Hormone-releasing Hormone (Gnrh) Agonistmentioning

confidence: 99%

“…HRT for POI is necessary regardless of the absence of presence of the desire to raise a child or maintain health 38 . In addition, recent animal studies have indicated that E2 has important roles in follicle development 39,40 . Follicle development is observed when gonadotropins are decreased during HRT.…”

Section: Current Treatment Of Poi For Obtaining Own Eggsmentioning

confidence: 99%

Follicle development and its prediction in patients with primary ovarian insufficiency: Possible treatments and markers to maximize the ability to conceive with residual follicles

Osuka,

Kasahara,

Iyoshi

et al. 2023

Reprod Medicine & Biology

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BackgroundPrimary ovarian insufficiency (POI) is characterized by the development of hypergonadotropic hypogonadism before 40 years of age and leads to intractable infertility. Although in vitro fertilization and embryo transfer with donated eggs enables pregnancy, not a few patients desire pregnancy using their oocytes. However, follicular development is rare and unpredictable in patients with POI. Thus, there is a need for treatments that promote the development of residual follicles and methods to accurately predict infrequent ovulation.MethodsThis review discusses the effects of various treatments for obtaining eggs from POI patients. Furthermore, this study focused a potential marker for predicting follicular growth in patients with POI.Main FindingsDifferent treatments such as hormone‐replacement therapy, dehydroepiandrosterone supplementation, platelet‐rich plasma injection, and in vitro activation have shown varying degrees of effectiveness in retrieving oocytes from patients with POI. To predict follicle development in the cycle, elevated serum estradiol and reduced follicle‐stimulating hormone (FSH) levels are important. However, these markers are not always reliable under continuous estradiol‐replacement therapy. As a novel marker for predicting follicle growth, serum anti‐Müllerian hormone (AMH) levels, measured using the picoAMH enzyme‐linked immunosorbent assay, were found to predict follicle growth in patients and the cycle.ConclusionThis review highlights the challenges and available interventions for achieving pregnancy using a patient's oocytes in cases of POI. We believe that a combination of currently available treatments and prediction methods is the best strategy to enable patients with POI to conceive using their own eggs. Although AMH levels may predict follicle growth, further research is necessary to improve the chances of successful follicular development and conception in patients with POI.

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“…Tamoxifen also affects ovarian follicles in rodents with effects that depend on the stage of follicular development and experimental design. Tamoxifen was shown to promote primordial follicle activation [13] and increase the number of primordial follicles [14] as well as the number of atretic and cystic follicles [15,16]. On the other hand, TAM decreased the number of healthy secondary and antral follicles and corpora lutea [14,15].…”

Section: Introductionmentioning

confidence: 99%

Molecular Action of Tamoxifen in the Ovaries of Rats with Mammary Neoplasia

Nynca,

Swigonska,

Molcan

et al. 2023

IJMS

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Tamoxifen (TAM) is a drug commonly used in patients with breast cancer. The anticancer effect of TAM occurs via its ability to antagonize estrogen-dependent growth of mammary epithelial cells. Previously, we demonstrated that TAM prevented the chemotherapy-induced loss of ovarian follicular reserves in both cancer-free rats and rats with cancer. Such follicular loss is a main cause of infertility in young women treated for cancer. The current study was undertaken to discover the molecules and intracellular pathways involved in the action of TAM in the ovaries of rats with mammary tumors. To meet this goal we used transcriptomic (RNA-Seq) and proteomic (2D-DIGE/MS) approaches. TAM inhibited the expression of genes and lncRNAs involved in ovarian steroidogenesis. Moreover, TAM altered the expression of genes related to primordial follicle activation or arrest. In addition, proteomic screening indicated the importance of basic metabolic processes in the ovarian actions of TAM. Although simple extrapolation of these data to humans is not possible, the results of this study emphasize the need to explore the ability of TAM to affect ovarian function in women undergoing cancer treatment.

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Tamoxifen Activates Dormant Primordial Follicles in Mouse Ovaries

Cited by 4 publications

References 38 publications

Impaired fertility in adenomyosis: a murine model reveals endometrial receptivity and progesterone resistance imbalances

Impaired fertility in adenomyosis: a murine model reveals endometrial receptivity and progesterone resistance imbalances

Follicle development and its prediction in patients with primary ovarian insufficiency: Possible treatments and markers to maximize the ability to conceive with residual follicles

Molecular Action of Tamoxifen in the Ovaries of Rats with Mammary Neoplasia

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