Kisspeptin is involved in ovarian follicular development during aging in rats.

We have previously reported that kisspeptin (KP) may be under the control of the sympathetic innervation of the ovary. Considering that the sympathetic activity of the ovary increases with aging, it is possible that ovarian KP also increases during this period and participates in follicular development. To evaluate this possibility, we determined ovarian KP expression and its action on follicular development during reproductive aging in rats. We measured ovarian KP mRNA and protein levels in 6-, 8-, 10- and 12-month-old rats. To evaluate follicular developmental changes, intraovarian administration of KP or its antagonist, peptide 234 (P234), was performed using a mini-osmotic pump, and to evaluate FSH receptor (FSHR) changes in the senescent ovary, we stimulated cultured ovaries with KP, P234 and isoproterenol (ISO). Our results shows that KP expression in the ovary was increased in 10- and 12-month-old rats compared with 6-month-old rats, and this increase in KP was strongly correlated with the increase in ovarian norepinephrine observed with aging. The administration of KP produced an increase in corpora lutea and type III follicles in 6- and 10-month-old rats, which was reversed by P234 administration at 10 months. In addition, KP decreased the number and size of antral follicles in 6- and 10-month-old rats, while P234 administration produced an increase in these structures at the same ages. In ovarian cultures KP prevented the induction of FSHR by ISO. These results suggest that intraovarian KP negatively participates in the acquisition of FSHR, indicating a local role in the regulation of follicular development and ovulation during reproductive aging.

Blocking of ß-adrenergic receptors during the subfertile period inhibits spontaneous ovarian cyst formation in rats.

As aging proceeds, fertility problems arise, and the success rate of in vitro fertilization declines. During reproductive aging, rat ovaries present spontaneous formation of cysts, followed by a concomitant increase in sympathetic nerve activity, causing infertility and cessation of ovarian function. ß2-Adrenergic receptors, which are activated by noradrenaline (NA), modify follicular development and steroid secretions; thus, increased nerve activity has been associated with the development and maintenance of cystic structures. The purpose of this work was to block the effect of this sympathetic activity through in vivo administration of propranolol (a ß-adrenergic receptor antagonist) to determine whether it delays cyst formation and cessation of the ovarian function in rats that had reached the subfertile period. Propranolol was administrated daily to 8- and 10-month-old rats for 2 months. Estrous cycling activity was monitored by vaginal smear, serum concentration of the steroidal hormones was determined by enzyme-immune assay and morphological analysis of the ovaries was performed using 6 µm tissue slices stained with hematoxylin-eosin. Propranolol increased the number of healthy follicles, the ovulation rate, and levels of serum sexual steroids (androstenedione, testosterone, and estradiol) and recovered estrous cycling activity. It also decreased the number of follicular cysts. These results suggest that the blockade of ß-adrenergic receptors recovered ovarian function during reproductive aging. It is suggested that propranolol induces a time-dependent extension of the subfertile window, and it could be used to increase the success rate of fertility programs in aging woman.