Effects of different cyclooxygenase inhibitors on prostaglandin E₂ production, steroidogenesis and ovulation of bovine preovulatory follicles

Abstract

Ovulation is an inflammation-like process, and cyclooxygenase-2 (COX-2)-dependent production of prostaglandin E 2 (PGE 2 ) is its key mediator. Balanced regulation of inflammatory processes in high-yielding dairy cows may be essential for physiological ovulation and fertility. This study aimed to elucidate the mechanisms underlying ovulation failure and cyst development after disturbing intrafollicular inflammatory cascades. Therefore, nonselective (indomethacin and flunixin-meglumine), COX-2 selective (meloxicam), and highly COX-2 selective (NS-398) inhibitors were injected into preovulatory follicles 16 h after administration of GnRH, and ovulation was monitored via ultrasound examination. Additionally, follicular fluid was collected after injection of indomethacin, meloxicam, and NS-398. Moreover, primary granulosa cell cultures from preovulatory follicles were prepared and treated with indomethacin, meloxicam, and NS-398. The concentrations of 17β-estradiol, progesterone, and prostaglandin E 2 (PGE 2 ) in the follicular fluid and cell supernatant were estimated. Indomethacin and flunixin-meglumine blocked ovulation, even at low doses, and led to ovarian cyst development. The selective and highly selective COX-2 inhibitors meloxicam and NS-398 were not effective in blocking ovulation. However, indomethacin, meloxicam, and NS-398 significantly and comparably reduced PGE 2 concentration in vivo and in vitro (P < 0.05) but had no effect on estradiol or progesterone production. This may contradict the generally accepted hypothesis that PGE 2 is a key mediator of ovulation and progesterone production. Our results suggest a connection between ovarian disorders and inflammatory actions in early postpartum cows.

Effect of indomethacin on embryo implantation and histomorphology of uterus, ovary, kidney, and liver of rats

“…On the other hand, IMC reliably blocked the ovulation of preovulatory follicles at low doses, leading to ovarian cyst development ( Tokmakov et al, 2020 , Vernunft et al, 2022 ). In an experiment conducted by (Orczyk, 1972) at a single dose of 7 mg/kg if IMC administered (SC) showed complete inhibition of ovulation when observed at 3.5 h prior to the expected ovulatory LH surge, while all rats were reported to ovulate after LH was administered 3 h after a dose of 1 mg/kg of IMC ( Orczyk & Behrman, 1972 ).…”

“…Prostaglandins play an important role in ovulation. In particular, prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) concentrations increase massively prior to ovulation ( Vernunft et al, 2022 ). In addition to limiting prostaglandin production and preventing follicular rupture with oocyte release ( Yavuz et al, 2021 ).…”