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- Author: Ariella Shikanov x
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Medical Scientist Training Program, University of Michigan, Ann Arbor, Michigan, USA
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Division of Reproductive Endocrinology and Infertility, University of Michigan, Ann Arbor, Michigan, USA
Department of Urology, University of Michigan, Ann Arbor, Michigan, USA
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Division of Reproductive Endocrinology and Infertility, University of Michigan, Ann Arbor, Michigan, USA
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Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA
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Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA
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Historically, research in ovarian biology has focused on folliculogenesis, but recently the ovarian stroma has become an exciting new frontier for research, holding critical keys to understanding complex ovarian dynamics. Ovarian follicles, which are the functional units of the ovary, comprise the ovarian parenchyma, while the ovarian stroma thus refers to the inverse or the components of the ovary that are not ovarian follicles. The ovarian stroma includes more general components such as immune cells, blood vessels, nerves, and lymphatic vessels, as well as ovary-specific components including ovarian surface epithelium, tunica albuginea, intraovarian rete ovarii, hilar cells, stem cells, and a majority of incompletely characterized stromal cells including the fibroblast-like, spindle-shaped, and interstitial cells. The stroma also includes ovarian extracellular matrix components. This review combines foundational and emerging scholarship regarding the structures and roles of the different components of the ovarian stroma in normal physiology. This is followed by a discussion of key areas for further research regarding the ovarian stroma, including elucidating theca cell origins, understanding stromal cell hormone production and responsiveness, investigating pathological conditions such as polycystic ovary syndrome (PCOS), developing artificial ovary technology, and using technological advances to further delineate the multiple stromal cell types.
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA
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Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA
Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA
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Department of Urology, University of Michigan, Ann Arbor, Michigan, USA
Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, Michigan, USA
Department of Women's Heath, Henry Ford Health, Rochester Hills, Michigan, USA
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Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA
Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, Michigan, USA
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In brief
Animal studies are needed to inform clinical guidance on the effects of testosterone gender-affirming hormone therapy (T-GAHT) on fertility. This review summarizes current animal models of T-GAHT and identifies gaps in knowledge for future study.
Abstract
Testosterone gender affirming hormone therapy (T-GAHT) is frequently used by transgender and gender-diverse individuals assigned female at birth to establish masculinizing characteristics. Although many seek parenthood, particularly as a gestational parent or through surrogacy, the current standard guidance of fertility counseling for individuals on testosterone (T) lacks clarity. At this time, individuals are typically recommended to undergo fertility preservation or stop treatment, associating T-therapy with a loss of fertility; however, there is an absence of consistent information regarding the true fertility potential for transgender and gender-diverse adults and adolescents. This review evaluates recent studies that utilize animal models of T-GAHT to relate to findings from clinical studies, with a more specific focus on fertility. Relevant literature based on murine models in post- and pre-pubertal populations has suggested reversibility of the impacts of T-GAHT, alone or following gonadotropin-releasing hormone agonist (GnRHa), on reproduction. These studies reported changes in clitoral area and ovarian morphology, including corpora lutea, follicle counts, and ovarian weights from T-treated mice. Future studies should aim to determine the impact of the duration of T-treatment and cessation on fertility outcomes, as well as establish animal models that are clinically representative of these outcomes with respect to gender diverse populations.
