Annalucia Darbey

University College London | UCL · Institute of Neurology

Male infertility and hypogonadism are clinically prevalent conditions with a high socioeconomic burden and are both linked to an increased risk in cardiovascular-metabolic diseases and earlier mortality. Therefore, there is an urgent need to better understand the causes and develop new treatments for these conditions that affect millions of men. Th...

Background Despite the increasing popularity of deliverable transgenics, a robust and fully validated method for targeting Leydig cells, capable of delivering long‐term transgene expression, is yet to be defined. Objectives We compared three viral vector systems in terms of their cell targeting specificity, longevity of gene expression and impact...

Male development, fertility, and lifelong health are all androgen-dependent. Approximately 95% of circulating testosterone is synthesized by the testis and the final step in this canonical pathway is controlled by the activity of the hydroxysteroid-dehydrogenase-17-beta-3 (HSD17B3). To determine the role of HSD17B3 in testosterone production and an...

Leukemia inhibitory factor (LIF), a pleiotropic cytokine belonging to the interleukin-6 family, is most often noted for its role in maintaining the balance between stem cell proliferation and differentiation. In rodents, LIF is expressed in both the fetal and adult testis; with the peritubular myoid (PTM) cells thought to be the main site of produc...

The Sertoli cells regulate differentiation and development of the testis and are essential for maintaining adult testis function. To model the effects of dysregulating Sertoli cell number during development or ageing we have used acute diphtheria toxin-mediated cell ablation to reduce Sertoli cell population size. Results show that the size of the...

Testicular Leydig cells (LCs) are the principal source of circulating testosterone in males. LC steroidogenesis maintains sexual function, fertility and general health, and is influenced by various paracrine factors. The leukemia inhibitory factor receptor (LIFR) is expressed in the testis and activated by different ligands, including leukemia inhi...

Leydig cells (LC) are the main testicular androgen-producing cells. In eutherian mammals, two types of LCs emerge successively during testicular development, fetal Leydig cells (FLCs) and adult Leydig cells (ALCs). Both display significant differences in androgen production and regulation. Using bulk RNA sequencing, we compared the transcriptomes o...

Leydig cells (LC) are the main testicular androgen-producing cells. In eutherian mammals, two types of LCs emerge successively during testicular development, fetal Leydig cells (FLCs) and adult Leydig cells (ALCs). Both display significant differences in androgen production and regulation. Using bulk RNA sequencing, we compared the transcriptomes o...

Testis development and function is regulated by intricate cell-cell cross talk. Characterization of the mechanisms underpinning this has been derived through a wide variety of approaches including pharmacological manipulation, transgenics, and cell-specific ablation of populations. The removal of all or a proportion of a specific cell type has been...

The tamoxifen-inducible Cre system is a popular transgenic method for controlling the induction of recombination by Cre at a specific time and in a specific cell type. However, tamoxifen is not an inert inducer of recombination, but an established endocrine disruptor with mixed agonist/antagonist activity acting via endogenous estrogen receptors. S...

Sertoli cells (SC) are key initiators of testis development and have a fundamental role in spermatogenesis. However, it is uncertain how an acute reduction in SC number, in a hormone independent-manner at key points in development or adulthood, will impact testis function. To induce acute SC-ablation at key points of testicular development, we used...