Testicular Physiology

Regulation of testicular polyamine production and study of their contributions to testicular physiology.

In our project we perform an in-depth analysis of the metabolism of polyamines (PAs) in a tissue that, a priori, would not be considered a “a main sorurce of PAs”. However, our preliminary results suggest that not only significant levels of PAs (in the order of mM) can be detected in the testis of our experimental model (the Syrian hamster) but that there are significant differences in the testicular concentration of the main PAs (putrescine , spermidine and spermine) in immature animals, young adults and aged adults. In this work, we dissect the testis into its most important and representative cellular constituents to identify those cell populations that contribute to the local production of PAs, trying to discern in what proportion they would be able to contribute to the metabolism of testicular PAs. Additionally, we explore in detail their complex system of synthesis, interconversion, catabolism, and transport and analyze which specific cellular functions could be impacted by the PAs in the testis.

Steroidogenesis, potassium channels and testicular aging.

The Project proposes to study the physiological process of aging in the testis by analyzing the leading role of Leydig cells and high-conductance potassium channels activated by calcium (BKCa, maxiK or Slo1). The central idea of our work is to focus on elucidating additional molecular regulatory mechanisms involved in Leydig cell steroidogenic pathway during aging. To this aim, we use different experimental strategies: the murine cell line TM3 (Leydig cells) and primary cell cultures of Leydig cells isolated from testes of physiologically-aged C57BL/6J mice and from murine models of accelerated aging [ due to overexpression of growth hormone (GH-Tg) ] or delayed aging [ either Ames Dwarf Prop1-/ dwarf mice, or GH-releasing hormone-deficient (GHRH-KO) mice ].

GDNF system in the cell populations of the spermatogonial stem cell niche.

Glial-derived neurotrophic factor (GDNF) is synthesized by cell populations of the spermatogonial stem cell niche (Sertoli and peritubular cells) and participates in the self-renewal, proliferation and survival of spermatogonial cells thus promoting a normal spermatogenesis. In this Project, we explore the possible regulatory molecular mechanisms exerted by local factors (3α-diol, testosterone, DHT, and melatonin) on the production of GDNF in stem cell niche-cells isolated from testes of immature Syrian hamsters. Additionally, two possible roles of GDNF are explored: as a protective agent of spermatogenic function (based on its antioxidant properties) and as a modulating agent of energy metabolism in Sertoli cells.

Neuroendocrine disruptors in the testis.

In this Project we plan to study the impact of various neuroendocrine disruptors on different cellular functions of the main testicular cell populations (e.g.: oxidative state, proliferation, apoptosis, autophagy, energy metabolism, and the local production of important factors). To this aim, we use cell lines and primary cell cultures of testicular cells obtained from Syrian hamsters.