No abstract

No abstract

A B S T R A C TBoth reproductive hormones and the mammalian target of rapamycin (mTOR) intracellular signalling system, including mTOR complex 1 (mTORC1), mTOR complex 2 (mTORC2) and its key enzyme sirtuin 1 (SIRT 1) are involved in the control of ovarian processes but the interrelationship between hormones and mTOR has been studied insufficiently. The aim of our in vitro experiments was to elucidate the involvement of mTOR in the control of basic ovarian cell functions and in mediating the action of upstream hormonal stimulators. In the first series of experiments, we examined the effect of the known hormonal regulators of ovarian functions, Follicle-Stimulating Hormone (FSH), oxytocin (OT) and insulin-like growth factor I (IGF-I) (all at 0, 1, 10 and 100 ng mLG 1 doses), on the accumulation of SIRT1 in porcine ovarian granulosa cells. In the second series of experiments, we examined the effects of mTOR blockers, PF 046 (an inhibitor of mTORC1) and WYE 687 (inhibitor of both mTORC1 and mTORC2) (both at a dose of 1 µg mLG 1 ) on both basal and FSHinduced (0, 1, 10 and 100 ng FSH mLG 1 doses) basic ovarian functions (proliferation, apoptosis and steroidogenesis) of cultured porcine granulosa cells. The accumulation of SIRT1, PCNA (a proliferation-related peptide) and Bax (an apoptosis-related peptide) was detected by immunocytochemistry. The release of progesterone (P4) and testosterone (T) was analysed by EIA. It was observed that either FSH or OT additions increased the SIRT1 accumulation in ovarian cells, whilst IGF-I addition decreased it. The PF 046, when given alone, inhibited ovarian cell proliferation but did not affect apoptosis or the release of P4 and T. The WYE 687, when added alone did not affect proliferation and apoptosis but inhibited the P4 and T release by ovarian cells. The FSH, when given alone, stimulated proliferation did not affect apoptosis and increased the release of both P4 and T. In the presence of PF 046, FSH did not significantly alter proliferation, induced apoptosis and suppressed the P4 and T release, i.e., this inhibitor of mTORC1 prevented the proliferation-stimulating effect induced by the pro-apoptotic action of FSH and inverted the stimulatory action of FSH on steroidogenesis. The WYE 687 prevented the effect of FSH on both proliferation and apoptosis, promoted the FSH-induced P4 release but did not affect the FSH action on the T output, i.e., the inhibition of both mTORC1 and mTORC2 inverted the FSH action on ovarian cell proliferation and apoptosis but not the action on steroidogenesis. Our observations suggest the following: (1) mTORC1 can be involved in the up-regulation of ovarian cell proliferation but not that of apoptosis and steroidogenesis (2) mTORC2 can be involved in the up-regulation of the release of both P4 and T but not the up-regulation of ovarian cell proliferation and apoptosis, (3) FSH is involved in the stimulation of ovarian cell proliferation and P4 and T release and (4) hormones (FSH, OT and IGF-I) can regulate ovarian mTOR and the ability of mTOR to mo...

No abstract

The present study investigated whether dietary turmeric (Curcuma longa L.) can improve rabbit reproduction, ovarian function, growth, or viability. Female New Zealand White rabbits were either fed a standard diet (n=15) or a diet enriched with 5 g (group E1) or 20 g (group E2) turmeric powder per 100 kg feed mixture (n=16 or 15, respectively). After 295 days, weight gain, conception and kindling rates, pup and mother viability, ovarian macro- and micro-morphometric indices, release of leptin in response to the addition LH, and the release of progesterone, testosterone and leptin by isolated ovarian fragments were analyzed. Dietary turmeric failed to affect ovarian length and weight but did increase the number of primary follicles (E2: 32.5% greater than control group), as well as the diameter of primary (E1: +19.4%, E2: +21.1%), secondary (E2: +41.4%), and tertiary (E1: +97.1%, E2: +205.1%) follicles. Turmeric also increased the number of liveborn (E1: +21.0%) and weaned (E1: +25.0%) pups and decreased the number of stillborn pups (E2: -87.5%) but did not affect weight gain, conception, or kindling rate. Furthermore, dietary turmeric decreased doe mortality during the first reproductive cycle (13.3% in control; 0% in E1; and 6.7% in E2) but not during the second cycle. In vitro, the ovaries of the turmeric-treated rabbits released more progesterone (E1: +85.7%, E2: +90.0%) and less testosterone (E2: -87.0%) and leptin (E2: -29.0%) than the ovaries of control rabbits. Moreover, LH decreased the leptin output of control rabbits but increased that of experimental rabbits. Therefore, it is likely that dietary turmeric improves pup viability and that it could promote rabbit fecundity by either (1) promoting the production of primary ovarian follicles or (2) stimulating the growth of follicles at all stages of folliculogenesis.