Presence of ovarian stromal aberrations after cessation of testosterone therapy in a transgender mouse model

Kinnear, Hadrian M; Hashim, Prianka H.; Cruz, Cynthia Dela; Chang, Faith L; Rubenstein, Gillian; Nimmagadda, Likitha; Elangovan, Venkateswaran Ramamoorthi; Jones, Andrea; Brunette, Margaret A.; Hannum, D Ford; Li, Jun Z.; Padmanabhan, Vasantha; Moravek, Molly B.; Shikanov, Ariella

doi:10.1093/biolre/ioad019

Cited by 6 publications

(5 citation statements)

References 48 publications

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“…Furthermore, a significant number of these cells showed staining for the macrophage markers CD68 and CD11b. Analysis of ovarian ribonucleic acid-sequencing between the age-matched controls and the ovaries from mice treated with testosterone for six weeks indicated upregulation of immunological pathways in the post-testosterone group ( Kinnear et al, 2023 ).…”

Section: Resultsmentioning

confidence: 99%

The relationship between gender and pharmacology

Younes

2024

Current Research in Pharmacology and Drug Discovery

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Section: Resultsmentioning

confidence: 99%

The relationship between gender and pharmacology

Younes

2024

Current Research in Pharmacology and Drug Discovery

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“…The group then conducted another study to better understand the impact of T washout on ovarian dynamics [23]. In this study, C57BL/6N mice were treated with either subcutaneous injections of T enanthate or control sesame oil for 6 weeks.…”

Section: Animal Models Of Gaht With Testosterone (T-gaht) (Table 1)mentioning

confidence: 99%

A Review of Animal Models Investigating the Reproductive Effects of Gender-Affirming Hormone Therapy

Raja,

Rubin,

Moravek

2024

JCM

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Gender-affirming hormone therapy (GAHT) is an important component in the process of transitioning for many transgender and gender-diverse (TGD) individuals. Multiple medical organizations recommend fertility preservation counseling prior to initiation of GAHT; however, there remains little high-quality data regarding the impact of GAHT on fertility and reproductive function. A PubMed literature review was performed using Boolean search operators linking keywords or phrases such as “mouse”, “rat”, “primate”, “animal model”, “transgender”, “gender”, “estrogen”, “testosterone”, “fertility”, and “fertility preservation”. Recent research has produced a number of animal models of GAHT that utilize similar hormonal regimens and produce similar phenotypic results to those used and observed in human patients. Specific to testosterone(T)-containing GAHT, animals demonstrate loss of menstrual cyclicity with therapy, resumption of menses on cessation of therapy, suppression of gonadotropin levels, and physical changes such as clitoromegaly. Models mimicking GAHT for transmasculine individuals in the peripubertal period demonstrate that pretreatment with GnRHa therapy does not modify the effects of subsequent T administration, which were similar to those described in adult models. Both models suggest promising potential for future fertility with cessation of T. With estradiol (E)-containing GAHT, animals exhibit decreased size of testicles, epididymis, and seminal vesicles, as well as ongoing production of spermatocytes, and seminiferous tubule vacuolization. Given the ethical challenges of conducting human studies in this area, high-fidelity animal models represent a promising opportunity for investigation and could eventually transform clinical counseling about the necessity of fertility preservation. Future studies should better delineate the interactions (if any exist) between treatment attributes such as dosing and duration with the extent of reversibility of reproductive perturbations. The development of models of peripubertal feminizing GAHT is an additional area for future work.

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“…A significant number of these cells also showed staining for the macrophage markers CD68 and CD11b. Comparing the age-matched controls and ovaries at 6 weeks on testosterone, the ovarian ribonucleic acid-sequencing revealed that the immunological pathways were upregulated post-testosterone [ 165 ].…”

Section: What About Transgender Models?mentioning

confidence: 99%

Evaluation of Sex Differences in Preclinical Pharmacology Research: How Far Is Left to Go?

Allegra,

Chiara,

Di Grazia

et al. 2023

Pharmaceuticals

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Until the last quarter of the 20th century, sex was not recognized as a variable in health research, nor was it believed to be a factor that could affect health and illness. Researchers preferred studying male models for a variety of reasons, such as simplicity, lower costs, hormone confounding effects, and fear of liability from perinatal exposure in case of pregnancy. Equitable representation is imperative for determining the safety, effectiveness, and tolerance of therapeutic agents for all consumers. Decades of female models’ underrepresentation in preclinical studies has resulted in inequality in the understanding, diagnosis, and treatment of disease between the sexes. Sex bias has been highlighted as one of the contributing factors to the poor translation and replicability of preclinical research. There have been multiple calls for action, and the inclusion of sex as a biological variable is increasingly supported. However, although there has been substantial progress in the efforts to include more female models in preclinical studies, disparities today remain. In the present review, we consider the current standard practice of the preclinical research setting, why the sex bias exists, why there is the need to include female models, and what risks may arise from continuing this exclusion from experimental design.

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Presence of ovarian stromal aberrations after cessation of testosterone therapy in a transgender mouse model

Cited by 6 publications

References 48 publications

The relationship between gender and pharmacology

The relationship between gender and pharmacology

A Review of Animal Models Investigating the Reproductive Effects of Gender-Affirming Hormone Therapy

Evaluation of Sex Differences in Preclinical Pharmacology Research: How Far Is Left to Go?

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