The upregulation of PTGS and PTGS
The upregulation of PTGS1 and PTGS2 in late gestation in mares could be linked to the high levels of estrogens produced by the fetoplacental unit. Estrogens are thought to be effective stimulators of prostaglandin production by potentially up regulating PTGS2 expression. Although a recent publication showed that letrozole, an aromatase inhibitor, did not affect the parturition or gestational lengths in mares, administration of letrozole was able to reduce circulating concentrations of PGFM (Esteller-Vico et al., 2017), showing an association between estrogen and systemic prostaglandin metabolites.
On the other hand, in estrous mares we observed a decreased expression of PTGS1 and PTGS2 in cervical tissues. For the ewe, the hormonal regulation of COX-2 has been widely investigated and the reproductive steroid hormones, progesterone and estradiol (Zhang et al., 2007), can increase the expression of COX-2 in the uterus and in the cervix. The results presented here for mares do not show a relationship between PGR and ESR1 with PTGS1 and PTGS2. Thus, we suggest that the modulation of COX-1 and COX-2 could be tissue, specie and reproductive stage dependent.
Conclusions Based upon qPCR expression, we can conclude that ESR1 and PGR showed the highest expression the cervix of estrous and diestrous mares, while PTGS1, PTGS2 and PTGER2 were upregulated in late pregnant mares. Consistently, immunolabeling for ESR1 and PGR was detected in nucleus and cytoplasm of epithelium of the endocervix and smooth muscle for all reproductive stages analyzed. ESR2 was detected in nucleus and cytoplasm of epithelium of the endocervix and smooth muscle during estrus and last pregnancy. PTGER2 and PTGER4 were detected in nucleus and cytoplasm of epithelium of the endocervix and cytoplasm of smooth muscle for all reproductive stages studied. These changes may reflect preparation of the equine cervix for subsequent parturition; however, this pathway is far from fully understood. We know that the cervix, as well as the rest of the female reproductive tract, responds to fluctuating levels of sex hormones in a tightly coordinated fashion with the ym express mg and tissues, but the biological mechanisms related to cervical changes in equine specie had not been studied yet, it is clear that there are several other information that needs further investigation.
Conflict of interest statement
Acknowledgments This work was supported by the Albert G. Clay Endowment, the Clay Visiting Scholar Fellowship of the University of Kentucky and São Paulo Research Foundation (FAPESP, 2015/00049-5). Also, we would like to thank Drs. Anthony Claes, Elisa Sant’Anna Monteiro da Silva and Igor Canisso for their assistance in tissue collections.
Introduction Cardiovascular disease, including coronary artery disease (CAD), stroke and peripheral vascular disease, is the leading cause of death among women . Normal menopause is associated with impaired vascular endothelial function 2, 3. Endothelial dysfunction contributes to the development of atherosclerosis , and the magnitude of this defect predicts cardiovascular events . Little is known about the effect of estrogen deprivation on cardiovascular pathophysiology in young women with premature ovarian failure (POF) (or premature menopause). POF is a condition characterized by sex-steroid deficiency, amenorrhea and infertility in women younger than 40 years of age . Young women with POF have estrogen deficiency for more years than do naturally menopausal women, resulting in a significantly higher risk for osteoporosis  and cardiovascular disease . Women with POF have a higher risk of premature death, mainly from cardiovascular causes 8, 9, 10, 11, 12, 13. However, until recently, very few studies have assessed the cardiovascular consequences of POF. Recent randomized trials have shown that hormone therapy increases the risk of cardiovascular disease in postmenopausal women 14, 15, 16, 17. These findings have led young women with POF and their physicians to wonder whether they should use or discontinue hormone therapy. The present review summarizes the current clinical evidence regarding the effects of estrogen deprivation and hormone replacement therapy on markers of cardiovascular disease in young women with POF. The value of the assessment of vascular endothelial function as a research tool is discussed and an outline of future research directions in the management of women with POF is presented.