Endocrine integration of fetal ovaries grafted under kidney capsule of unilaterally or bilaterally orchidectomized male hamster / Integración endocrina de ovarios fetales trasplantados bajo la cápsula renal de hámster machos uni o bilateralmente castrados

Mammalian ovary development undergoes important changes during the perinatal period, moment when follicles are assembled and start to develop in a process not well known, involving endocrine and paracrine factors. In order to investigate the effect of two different hormonal environments on the early development of the ovary, we used an autologous transplant model in which Syrian hamster fetal ovaries were grafted under the kidney capsule of males hosts previously unilaterally or bilaterally orchidectomized. After 35 days of graft, ovaries and kidney parenchyme of the host male did not present signs of rejection. Ovaries contained primordial, primary follicles, secondary follicles and few tertiary follicles with morphological features similar to ovaries of control females of 35 days of age. Healthy primary and secondary follicles of experimental groups had frequency distribution and size similar to control ovaries but tertiary follicles were scarce in control as well as in grafts where they were mainly atretic. PCNA, marker of proliferation, was immuno detected in granulosa cells of growing follicles and the marker of apoptosis, Caspase 3 active, was evident mainly in secondary follicles. Immunoreactivity for steroidogenic proteins, StAR, 3-bHSD and aromatase detected in the follicular wall cells and the decreased serum levels of FSH without important changes in testosterone in bilateral orchidectomized males that received ovarian graft, and testosterone decreased without changes in FSH levels in unilateral orchidectomized males (UO) with ovarian graft, all together suggest the effect of steroid hormones produced by the ovary. In conclusion, the experimental model of autologous transplant presents evidence of early ovary development under the kidney capsule and its functional integration to the endocrine axis of the host male.

El desarrollo del ovario en mamíferos sufre importantes cambios durante el periodo perinatal, momento en el cual los folículos se ensamblan y comienzan a desarrollarse en un proceso no muy dilucidado que involucra señales endocrinas y paracrinas. Con el objetivo de investigar el efecto de dos ambientes hormonales sobre el desarrollo temprano del ovario de hamster, usamos un modelo de trasplante autólogo en el que ovarios fetales fueron trasplantados bajo la cápsula renal de machos receptores previamente castrados y hemicastrados. Después de 35 días de trasplante, los ovarios y el parénquima renal de los machos receptores no presentaron señales de rechazo. El ovario presentó folículos primordiales, primarios, secundarios y algunos folículos terciarios con características morfológicas similares a los ovarios de hembras controles de 35 días de edad. Folículos primarios y secundarios sanos de ambos grupos experimentales se encontraron en frecuencia y tamaño similar al de ovarios controles, los folículos terciarios fueron escasos tanto en controles como en ovarios trasplantados, siendo en éstos principalmente atrésicos. PCNA, un marcador de proliferación celular, fue detectado por inmunohistoquímica en células granulosas de folículos en crecimiento, mientras que caspasa 3 activa, un marcador de apoptosis, fue evidente en folículos secundarios. Por otra parte, inmunoreactividad para proteínas esteroidogénicas, StAR, 3-bHSD y aromatasa, fue detectada en la pared folicular. Esta observación, junto a la disminución de niveles séricos de FSH, sin cambios importantes en los niveles de testosterona en machos castrados que recibieron trasplantes ováricos, y la disminución en los niveles de testosterona sin cambios en los niveles de FSH en machos hemicastrados con trasplantes ováricos, sugiere que el ovario no solo produce hormonas esteroidales sino que además éstas modifican los niveles hormonales del macho receptor del trasplante. En conclusión, este modelo de trasplante autólogo agrega información del desarrollo ovárico temprano cuando éste se desarrolla bajo la cápsula renal de machos entregando evidencia de la integración funcional del ovario trasplantado al eje endocrino de los machos receptores.

In vivo ß-adrenergic blockade by propranolol prevents isoproterenol-induced polycystic ovary in adult rats.

Increasing evidence in animal models and in humans shows that sympathetic nerve activity controls ovarian androgen biosynthesis and follicular development. Thus, sympathetic nerve activity participates in the follicular development and the hyperandrogenism characteristics of polycystic ovary syndrome, which is the most prevalent ovarian pathology in women during their reproductive years. In this study, we mimic sympathetic nerve activity in the rat via "in vivo" stimulation with isoproterenol (ISO), a ß-adrenergic receptor agonist, and test for the development of the polycystic ovary condition. We also determine whether this effect can be reversed by the administration of propranolol (PROP), a ß-adrenergic receptor antagonist. Rats were treated for 10 days with 125 µg/kg ISO or with ISO plus 5 mg/kg PROP. The ovaries were examined 1 day or 30 days following drug treatment. While ISO was present, the ovaries had an increased capacity to secrete androgens; ISO + PROP reversed this effect on androgen secretory activity. 30 days after treatment, androstenedione secretion reverted to normal levels, but an increase in the intra-ovarian nerve growth factor (NGF) concentration and luteinizing hormone (LH) plasma levels was detected. ISO treatment resulted in follicular development characterized by an increased number of pre-cystic and cystic ovarian follicles; this was reversed in the ISO + PROP group. The lack of change in the plasma levels of progesterone, androstenedione, testosterone, or estradiol and the increased LH plasma levels strongly suggests a local intra-ovarian effect of ISO indicating that ß-adrenergic stimulation is a definitive component in the rat polycystic ovary condition.

Role of stress and sympathetic innervation in the development of polycystic ovary syndrome

This work attempts to give a review of ovarian innervation, the mechanism of regulation of nerve activity and the role of the sympathetic activity in ovarian pathologies affecting reproductive function. We provide a succinct outline of the findings of our group in this area. The participation of stress as an etiological factor for ovarian pathologies throughout animal models and preliminary data in patients with polycystic ovary syndrome give strong support for a participation of sympathetic nerves in the ovary function both in normal and pathological states.

Changes in sympathetic nerve activity of the mammalian ovary during a normal estrous cycle and in polycystic ovary syndrome: Studies on norepinephrine release.

Although it has been known for many years that the ovary is innervated by catecholaminergic nerve fibers and much experimental evidence has strengthened the notion that catecholamines are physiologically involved in the control of ovarian function, scarce evidence has been presented as to the role of sympathetic activity in ovarian pathologies that affect reproductive function. The purpose of this article is to provide a succinct overview of the findings in this area and discuss them relative to the pathology of polycystic ovary syndrome, the most common ovarian pathology in women during their reproductive years.