Ovarian Follicle Vascularization in Mammals with Special Regard to Domestic Animals

Abstract

G. Macchiarelli*, A. Martelli**, V. Russo**, P. Berardinelli**, M.G. Palmerini*, S.A. Nottola***, J.Y. Jiang**** and E. Sato***** * Department of Experimental Medicine, University of L’Aquila, Italy ** Department of Comparative Biomedical Sciences, University of Teramo, Italy *** Department of Anatomy, University of Rome La Sapienza, Italy **** Ottawa Health Research Institute, Ottawa Hospital, Ontario, Canada ***** Lab. of Animal Reproduction, Faculty of Agriculture, Tohoku University of Sendai, Japan The ovarian function during reproductive life is related to a normal development of blood vessel neoformation and consequently to the expression of several factors that may upregulate/downregulate follicle and corpus luteum angiogenesis [1,2]. Follicle activation involves vascular endothelial growth factor production and increases blood vessels extension. Numerous morphological studies, mainly performed by means of vascular casting media, analysed the distribution and cyclical rearrangement of ovarian blood vessels in several mammals, in different experimental conditions [3]. Despite the wide literature on the blood vessel distribution in the mammalian ovary, only a few information is available on ovarian angiogenic morphological aspects of developing and atretic follicles, especially in domestic animals, that shows morphofunctional characteristics of the ovarian follicle more similar to humans than rodent models. In addition, it is not yet clear which morphological aspects are related to a correct angiogenesis and capillary regression, especially when evaluated in the light of species differences. Therefore, in order to better understand the morphological mechanisms regulating the microvascular changes occurring in the theca layer before ovulation of larger follicles, we have reviewed by scanning electron microscopy (SEM) of vascular corrosion casts (VCC) the ovarian microvasculature in different experimental conditions, in rodents and domestic animals. Rat, rabbit, pig, sheep, and cow ovaries, at different reproductive stages and or/subjected to different protocols of hormonal stimulation were studied. Rat model was used as control. Rabbit was chosen as a model for reflex ovulation [4]; pig [2,5,6] and sheep [7] as multiovulatory species and cow [8] as a monovulatory model similar to humans. SEM of CC was adopted because it is one of the technique of choice for 3D visualization of blood vessels and capillary network arrangements [4]. Methods and hormonal protocols were previously described [2, 4-9]. An intensive functional and morphological remodeling of cortical venules and arterioles accompanied follicle development [9]. Follicle angiogenesis was demonstrated during follicular maturation in all species studied [3]. SEM of VCC demonstrated the differentiation of several microstructures, namely buds, sprouts (sprouting angiogenesis) and intussusceptions (non sprouting angiogenesis) that allowed firstly the growth, then the duplication and multiplication of the preexisting capillaries. The gradual formation of a dense sinusoidal network supplying the theca layer of fully developed follicles (dominant) was also clearly shown. Atretic and subordinated follicles presented degenerative microvascular structures such as thinned capillaries and avascular areas. Species differences were related to follicle size and to mechanisms of follicle selection. In rodents, significant angiogenic morphological figures were mainly confined to the capillaries of the inner thecal layer. In larger follicles of domestic animals vascular remodeling and angiogenic