Protective role of melatonin in progesterone production by human luteal cells

Abstract

This study investigated whether melatonin protects luteinized granulosa cells from reactive oxygen species (ROS) as an antioxidant to enhance progesterone production in the follicle during ovulation. Follicular fluid was sampled at the time of oocyte retrieval in women undergoing in vitro fertilization and embryo transfer (IVF-ET). Melatonin concentrations in the follicular fluid were positively correlated with progesterone concentrations (r = 0.342, P < 0.05) and negatively correlated with the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker (r = -0.342, P < 0.05). The progesterone and 8-OHdG concentrations were negatively correlated (r = -0.246, P < 0.05). Luteinized granulosa cells were obtained at the time of oocyte retrieval in women undergoing IVF-ET. Cells were incubated with H(2)O(2) (30, 50, 100 μm) in the presence or absence of melatonin (1, 10, 100 μg/mL). Progesterone production by luteinized granulosa cells was significantly inhibited by H(2)O(2). Melatonin treatment overcame the inhibitory effect of H(2) O(2) . Twenty-five patients who had luteal phase defect (serum progesterone concentrations <10 ng/mL during the mid-luteal phase) were divided into two groups during the next treatment cycle: 14 women were given melatonin (3 mg/day at 22:00 hr) throughout the luteal phase and 11 women were given no medication as a control. Melatonin treatment improved serum progesterone concentrations (>10 ng/mL during the mid-luteal phase) in nine of 14 women (64.3%), whereas only two of 11 women (18.1%) showed normal serum progesterone levels in the control group. In conclusion, melatonin protects granulosa cells undergoing luteinization from ROS in the follicle and contributes to luteinization for progesterone production during ovulation.

Melatonin deprival modifies follicular and corpus luteal growth dynamics in a sheep model

“…However, the presence of high melatonin levels in follicular fluid (Brzezinski et al 1987) and the presence of receptors in granulosa cells (Yie et al 1995, Niles et al 1999, Woo et al 2001, Soares et al 2003a, Wang et al 2012, Barros et al 2013 have suggested a role of melatonin on ovarian function. This hypothesis has been confirmed by recent studies reporting strong evidence for melatonin action on the ovary, such as modulation of ovarian steroidogenesis (mainly progesterone (P 4 ) production; Taketani et al 2011) and contribution in the maintenance of a proper follicular structure and function (Soares et al 2003a,b, Barros et al 2013, Maganhin et al 2013. In a previous study, we demonstrated that melatonin supplementation during the anoestrous period modifies the pattern of follicular waves by increasing the turnover of dominant follicles (Berlinguer et al 2009).…”

Essential actions of melatonin in protecting the ovary from oxidative damage

“…The ovulatory process is similar to a local inflammatory response, resulting in high levels of reactive species [83] among which ROS may potentially damage granulosa cells undergoing luteinization during ovulation [89]. As in folliculogenesis, melatonin has a variety of functions at different luteal stages.…”

A pilot study to search possible mechanisms of ultralong gonadotropin-releasing hormone agonist therapy in IVF-ET patients with endometriosis

“…The sensitivity of 8-OHdG was 0.5 ng/ml, and the CV for intra-and inter-assay were 5.5% and 6.1%, respectively. HEL concentrations were measured using an ELISA kit (Japan Institute for the Control of Aging) as we reported previously [26,27]. Each sample of follicular fluid (50 μl) was pretreated with chymotrypsin to perform proteolysis, and filtered using an ultrafilter (cut off molecular weight 10 kDa) for duplicate assay.…”