Structural bases of the ovarian function: An introduction

Renewing the life is the extraordinary fate of germ cells. The mammalian ovary is the main host of the series of intriguing and complicated events that have led primitive oogonia to slowly mature into highly selected oocytes, competent for fertilization (Motta et al., 2003). The technological improvements of the last decades have provided opportunities for researchers to understand many of the basic processes of mammalian biology of reproduction in humans. Many ‘‘hot topics’’ are under active investigation today using a morphological approach, especially at microscopic level, that is providing important insights into the structural basis of ovarian physiopathology. Indeed, (a) how oocyte precursors colonize the ovarian tissue during embryonic life (Pereda and Motta, 1991); (b) the process of oogonia differentiation (Sathananthan et al., 2000); (c) the construction of the cell machinery of the mature oocyte and of its surrounding unique extracellular matrix compounds (Cecconi, 2002; Familiari et al., 1992); (d) the establishment of the physical and functional interrelationships between oocyte and somatic elements (Motta et al., 1994; Yokoo and Sato, 2004); (e) the development, differentiation, rearrangement, and interactions of somatic cells forming the ovarian follicles (Tajima et al., 2002); (f) the expression of the thecal capillary neoformation, self-regulated by the ‘‘stop and go’’ of a unique angiogenetic process (Macchiarelli, 2000); (g) the morphodynamic and pathophysiology of the epithelium investing ovarian surface (Okamura and Katabuchi, 2005); (h) the competence of the immune system in regulating the ovarian function and the expression of cancer (Bukovsky et al., 1995); (i) the fine tuning of local hemodynamic in ovarian subcompartments and the selection of the dominant follicle (Hunter et al., 2000); (j) the morphological expression of granulosa cells in in-vitro models (Fabbri et al., 2000; Nottola et al., 1991) are a research topic, in many research fields, that deserve a special approach using a morphofunctional point of view. The ovary, in fact, is characterized by great functional plasticity that is necessary to maintain its reproductive competence. The cyclical morphodynamic changes in ovarian tissue architecture underlie this plasticity since the first signs of active gonadal rearrangement can be found early in development, when oogenesis starts and the formation of the early follicles takes place. All steps in ovarian morphodynamics are in tune with intraand extra-ovarian signals, thanks to the interplay between germ and somatic cell lines, which differ in origin and function but express close direct and indirect physical interrelationships. The correlation of tissue morphodynamics with functional and pathological events occurring in ovarian tissue is a central objective in the biology of reproduction, so as to identify the structural and even ultrastructural markers of normal, pathological, and experimental conditions. Ovarian tissue shows different macro and micro functional domains that correspond to specific well known tissue compartments and many—less understood—cellular subcompartments. These microdomains are expressed by several morphofunctional events including (1) the rearrangement of the organelles in premeiotic germ cells and maturing oocytes; (2) the establishment of cellular contacts between germ cells and the surrounding somatic cells in the blastema of the fetal ovary and during follicle maturation or ovulation; (3) the zona pellucida dynamics accompanying oocyte growth, maturity, fertilization, or atresia; (4) the endocrine, paracrine and immunological signal traffic between granulosa and theca internal compartments; (5) the follicular selection through a programmed activation of mechanisms of cell death in germ, somatic, and supporting elements as well; (6) the structural and functional microvascular dynamics during growth and demise of the follicular-luteal complex; (7) the changes of extra-follicular somatic elements in normal and pathological conditions and finally, (8) the morphological adaptation of both oocyte and granulosa elements to an extracorporeal management in culture as occurring during the most recent assisted reproduction technology (ART) applications. All these aspects should be taken into consideration when evaluating the viability of any sampled ovarian tissue in reproductive medicine. The application of various classic and new microscopic techniques, associated with methods of biochemical and tissue characterization of several molecules expressed in the ovary, has undoubtedly allowed a detailed understanding of the above complex processes. However, several crucial points still remain to be elucidated. In particular, timing and localization of germ cell separation from the somatic cell line and the influence of germ cell on the ovary differentiation are still being actively investigated. In addition, the origin of ovarian blastema and follicular cell precursors are not completely understood. Similarly, the early events triggering the selective degenerative processes of germ and somatic cells before and after birth are not yet understood. Whether or not germ cell number is fixed early in life, according to a fundamental dogma in reproductive science, or whether germline stem cells remain capable of postnatal renewal and it does occur in the adult ovary is an old debate that has very recently received new attention (Johnson et al., 2004, 2005), but has not been resolved. The primary signals driving follicular development and ovulation also remain undetermined. In particular, a great deal of work has been expended in the attempt to understand which factors stimulate recruitment of primordial follicles and are responsible for subsequent dominant follicle selection. Of course, all the earlier mentioned are important topics in basic science, but the question is which ones will have the greatest impact on applied and clinical research? Understanding the mechanisms of germ cell formation in the embryo and the mechanisms by which they self regulate their totipotency could foster the management of these cells in vitro, and