Brain-derived neurotrophic factor (BDNF), an autocrine/paracrine regulator of basic ovarian functions and antagonist of kisspeptin.

The aim of the present study was to examine whether brain-derived neurotrophic factor (BDNF) and BDNF-related molecules, such as the neuronal membrane glycoprotein M6a (GPM6A) and myocyte enhancer factor 2C (MEF2C), can be produced by ovarian cells and regulate ovarian cell functions as well as elucidate its functional interrelationships with the known regulator of ovarian cell functions kisspeptin (KP). For this purpose, we analyzed the expression of BDNF and GPM6A in rat ovaries and of BDNF, GPM6A and MEF2C in porcine ovarian granulosa cells; the influence of KP addition on the expression of BDNF, GPM6A and MEF2C; and the effects of BDNF, KP and the combination of BDNF + KP treatment on the proliferation, apoptosis and release of progesterone and estradiol by cultured porcine granulosa cells. The expression of BDNF, GPM6A and MEF2C was quantified by qPCR, and proliferation, apoptosis and hormone release were analyzed by BrdU incorporation, TUNEL and ELISA. Our results demonstrate that both rat and porcine ovarian cells express BDNF and related molecules. Furthermore, the addition of BDNF stimulates the proliferation and release of progesterone and reduces the degree of apoptosis and estradiol output by porcine cells. KP has the opposite effect on these parameters. Furthermore, KP reduces the expression of BDNF and GPM6A but not MEF2C and suppresses the effects of BDNF on porcine granulosa cell apoptosis as well as progesterone and estradiol release. These observations are the first to demonstrate (1) the production of BDNF, GPM6A and MEF2C in the ovary, (2) the ability of BDNF to regulate ovarian cell proliferation, apoptosis and steroid hormone release by porcine ovarian cells, and (3) the antagonism between BDNF and KP production and their control of ovarian functions.