Comprehensive profiling of prostaglandins in human ovarian follicular fluid using mass spectrometry

Abstract

Prostaglandins are formed by enzymatic and non-enzymatic mechanisms. They have been detected in human ovarian follicular fluid (HFF), a medium rich in growth factors and nutrients important for oocyte growth and fertility. However, the comprehensive identification of HFF prostaglandins has not been addressed. Here we use hybrid triple quadrupole time-of-flight and triple quadrupole mass spectrometers to comprehensively analyze prostaglandins in HFF. We identified PGE1, PGE2, PGF2α, and other prostaglandins synthesized via prostaglandin-endoperoxide synthase (i.e. Cox) cascades. We also identified specific PGF2α isomers (F2-isoprostanes) and PGF3α analogs whose structures are inconsistent with Cox-dependent formation. A prospective cohort pilot study of infertility patient subtypes revealed two potential associations. F2-isoprostanes are decreased in the diminished ovarian reserve subtype and elevated PGF2α may be associated with decreased live birth. Other than PGF2α, only body mass index >25kg/m correlated with poor in vitro fertilization outcome. Our studies suggest that HFF contains prostaglandins formed from at least two mechanisms, which may correlate with distinct clinical parameters.

Antimüllerian Hormone and Oxidative Stress Biomarkers as Predictors of Successful Pregnancy in Polycystic Ovary Syndrome, Endometriosis and Tubal Infertility Factor

“…It is also known that several different prostaglandin derivatives are present in the follicular fluid. 47,66 We estimate that this assay is not good for testing in follicle fluid and therefore no significant conclusions can be drawn from concentrations in this analyze. Due to the lack of clarity and poor research, further studies are needed.…”

“…Instead, they suggested that F2-isoprostanes in FF may have functions unrelated to stress or inflammation. 63 To date, we have not found any other researches that would measure 8-IP in follicular fluid. Some studies measured peritoneal fluid and plasma levels of 8-IP in vivo in patients with endometriosis.…”

Inflammation and Ovulation

“…Excess consumption of nonsteroidal anti-inflammatory drugs, which inhibit prostaglandin-endoperoxide synthase (cyclooxygenase or Cox), is associated with reversible female infertility, likely due to failed ovulation. On the other hand, proinflammatory cytokines increase PGF2α associated with corpus luteum development and immune cell recruitment [17].…”

International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin E2Receptors (EP1–4) and Prostacyclin Receptor (IP): Specific Roles in Pathophysiologic Conditions

“…PGs have been shown to play a remarkable role in the female reproductive system. PGE 1 , PGE 2 , and PGF 2 α are detectable in human ovarian follicular fluid ( Pier et al, 2018 ). Functionally, PGE 2 seems to be important for ovulation because it is mainly synthesized within the follicle and acts as an essential mediator in the gonadotropin-induced ovulation ( Goldberg and Ramwell, 1975 ).…”