Schjenken, J.E.Robertson, S.A.2020-09-102020-09-102020Physiological Reviews, 2020; 100(3):1077-11170031-93331522-1210http://hdl.handle.net/2440/127468Seminal fluid is often assumed to have just one function in mammalian reproduction - delivering sperm to fertilize oocytes. But seminal fluid also transmits signaling agents that interact with female reproductive tissues to facilitate conception and pregnancy. Upon seminal fluid contact, female tissues initiate a controlled inflammatory response that affects several aspects of reproductive function to ultimately maximize the chances of a male producing healthy offspring. This effect is best characterized in mice, where the female response involves several steps. Initially, seminal fluid factors cause leukocytes to infiltrate the female reproductive tract and selectively target and eliminate excess sperm. Other signals stimulate ovulation, and induce an altered transcriptional program in female tract tissues that modulates embryo developmental programming, and initiates immune adaptations to promote receptivity to implantation and placental development. A key result is expansion of the pool of regulatory T cells that assist implantation by suppressing inflammation, mediating tolerance to male transplantation antigens, and promoting uterine vascular adaptation and placental development. Principal signaling agents in seminal fluid include prostaglandins and transforming growth factor-β. The balance of male signals affects the nature of the female response, providing a mechanism of 'cryptic female choice' that influences female reproductive investment. Male-female seminal fluid signaling is evident in all mammalian species investigated including human, and effects of seminal fluid in invertebrates indicate evolutionarily conserved mechanisms. Understanding the female response to seminal fluid will shed new light on infertility and pregnancy disorders, and is critical to defining how events at conception influence offspring health.en© 2020 the American Physiological SocietyCytokines; fertility; maternal tolerance; pregnancy; reproduction; seminal fluid; Treg cellsJournal article100001321710.1152/physrev.00013.20180005577715000052-s2.0-85085078529517236Schjenken, J.E. [0000-0001-6293-6160]Robertson, S.A. [0000-0002-9967-0084]