The Effect of Coumestrol on Progesterone and Prostaglandin Production in the Mare: In Vitro and In Vivo Studies

Abstract

Coumestrol (Cou) is a plant-derived phytoestrogen that induces various pathologies in the female reproductive tract. Although effects of phytoestrogens on reproductive function in other species are well documented, their influence on progesterone (P) and prostaglandin (PG) secretion in the mare is unknown. The aim of this study was to determine if Cou directly affects P and PG concentrations (in vivo) and endometrial PG secretion (in vitro) in the mare. In experiment 1, the mares (n = 4) were fed for 14 days on a diet containing increasing proportions of alfalfa pellets (250 g-1 kg/day). An additional 4 mares were fed a standard diet (control group). Sequential blood samples were obtained for 8 h after feeding on Days 13 and 14 (1 kg/day alfalfa pellets). Feeding the mares alfalfa pellets up-regulated PGE and 13,14-dihydro-15-ketoprostaglandin F (PGFM) and down-regulated P in the blood plasma compared to those in the control group (P < 0.05). In experiment 2, epithelial and stromal cells were exposed to E (10 M) or Cou (10 M) for 24 h. In the in vitro study, Cou increased PG secretion in epithelial and stromal cells (P < 0.05). In both types of endometrial cells, Cou up-regulated PTGS-2 protein expression (P < 0.05). Moreover, PGES and PGFS proteins were up-regulated by Cou in epithelial cells (P < 0.01). These results indicate that Cou can disturb reproductive function by affecting reproductive hormone secretion and altering the endometrial milieu through PG stimulation. Coumestrol therefore may impair physiologic regulation of the estrous cycle and early pregnancy.

Phytoestrogens: A Review of Their Impacts on Reproductive Physiology and Other Effects upon Grazing Livestock

“…Even though analysis identified a broad range of phytoestrogens in the pasture samples consumed, the results of the samplings were inconclusive. Subsequent research comparing mares to cows and ewes identified that mares may also experience temporary infertility, in some instances as rapidly as 14 days following lucerne ingestion [ 74 ]. After exposure to lucerne for a minimum of 14 days, lack of ovulation, uterine edema and fluid accumulation were recorded in all eight mares in the trial ( Figure 7 ) [ 74 ].…”

“…Subsequent research comparing mares to cows and ewes identified that mares may also experience temporary infertility, in some instances as rapidly as 14 days following lucerne ingestion [ 74 ]. After exposure to lucerne for a minimum of 14 days, lack of ovulation, uterine edema and fluid accumulation were recorded in all eight mares in the trial ( Figure 7 ) [ 74 ]. Ferreira-Dias et al [ 31 ] also observed uterine edema and persistent anovulatory follicles in mares fed on a lucerne diet.…”

“…Ferreira-Dias et al [ 31 ] also observed uterine edema and persistent anovulatory follicles in mares fed on a lucerne diet. Two to three weeks after removal from lucerne hay, uterine edema regressed and cyclicity resumed in the mares [ 31 , 74 ]. Coumestrol was also found to increase in vivo and in vitro production and secretion of uterine prostaglandin [ 74 ] resulted in reduced levels of progesterone concentration in the blood plasma [ 74 ].…”

“…Two to three weeks after removal from lucerne hay, uterine edema regressed and cyclicity resumed in the mares [ 31 , 74 ]. Coumestrol was also found to increase in vivo and in vitro production and secretion of uterine prostaglandin [ 74 ] resulted in reduced levels of progesterone concentration in the blood plasma [ 74 ]. Coumestrol was noted to be a stronger stimulator of prostaglandin when compared to 17β-estradiol [ 74 ].…”

“…Coumestrol was also found to increase in vivo and in vitro production and secretion of uterine prostaglandin [ 74 ] resulted in reduced levels of progesterone concentration in the blood plasma [ 74 ]. Coumestrol was noted to be a stronger stimulator of prostaglandin when compared to 17β-estradiol [ 74 ]. The study by Szóstek et al [ 74 ] suggests that phytoestrogens may directly disrupt reproductive efficiency and uterine function by modulating the ratio of prostaglandin F2 alpha:dinoprostone (PGF 2a :PGE 2 ), leading to high, nonphysical production of luteolytic PGF 2a during the estrous cycle and early pregnancy.…”