Serum amyloid a: Expression throughout human ovarian folliculogenesis and levels in follicular fluid of women undergoing controlled ovarian stimulation

Abstract

Background: Serum amyloid A (SAA) is an acute phase protein expressed primarily in the liver in response to various injuries and inflammatory stimuli and is recognized as a modulator of inflammation. Ovarian reproductive functions including folliculogenesis and ovulation use inflammatory processes; thus, studying SAA in this context is of interest. Objectives: We investigated the expression and localization of SAA in ovarian developing follicles and its levels in follicular fluids. MethodsandParticipants: Nonradioactive in situ hybridizationandimmunohistochemical staining were applied on ovarian paraffin tissue sections. ELISA and RT-PCR were applied on follicular aspirates and blood samples from women undergoing controlled ovarian stimulation for in vitro fertilization. Results: Expression of SAA mRNA and protein was found in follicular cells at all stages of follicular development, from primordial and primary follicles through antral follicles and corpora lutea. Expression was observed in granulosa, theca and luteal cells, and oocytes. Expression of SAA was also found in granulosa cells recovered from follicular aspirates. The SAA protein was detected in follicular fluids. Its levels were somewhat lower than in peripheral blood with strong correlation between the two compartments and with significant correlation with patient's body mass index. High follicular fluid SAA levels were associated with reduced pregnancy rate. Conclusions: SAA is locally produced in ovarian developing follicles and is a constituent of follicular fluids, suggesting its role within the follicular environment. Elevated follicular SAA levels are associated with decreased pregnancy rate and may signify lower reproductive performance. (J Clin Endocrinol Metab 98: 4970-4978, 2013) Serum amyloidA(SAA) is an acute phase protein whose level in the blood is elevated up to 1000-fold in response to various inflammatory stimuli, including tissue injury, infection, and neoplasia (1). The liver is the major site of SAA production; however, extrahepatic expression was described in the epithelium of normal tissues (2), in adipose tissues (3), in diseased © 2013 by The Endocrine Society.