The role of seminal plasma in supporting successful embryo implantation

Conventionally it was believed seminal fluid had just one biological function, to support delivery of spermatozoa into the female tract, thereby facilitating fertilisation of the oocyte. There is increasing evidence indicating seminal fluid plays a more complex role, with studies conducted in mice revealing a critical effect of seminal fluid in initiating inflammatory changes in the female reproductive tract important for the establishment of immune tolerance that is required for successful pregnancy to occur. This tolerogenic immune environment is established at coitus prior to and at the time of conception, when contact with the conceiving male partner’s seminal fluid primes the female immune response. Immune tolerance is induced when seminal fluid delivers an array of signalling molecules that interact with the female reproductive tissues. The actions of immune cells responding to these signals in the cervix, uterus and ovary facilitate the likelihood of successful conception and pregnancy, by promoting clearance of seminal debris and microbes, inducing regulatory T cells to modulate the female immune response to male histocompatibility antigens, and conditioning the uterine environment in preparation for embryo implantation. In humans, this response is not as well characterised, however clinical studies have shown seminal fluid contact following intercourse provokes an adaptive immune response within the cervical tissues of women, and the transport of spermatozoa to the higher tract suggests a potential role in affecting the endometrial lining of the uterus directly. Further, seminal fluid exposure has been linked with both acute and cumulative benefits to pregnancy outcome, suggesting the immune response is physiologically important, long-lasting, and additive. Epidemiological studies show that pregnancy pathologies leading to prematurity and low birth weight occur more frequently in women where exposure to partner’s semen is limited or where seminal signalling is compromised. However, basic understanding of the female reproductive tract response to seminal fluid signals remains incomplete, limiting our capacity to develop diagnostics and design therapeutic interventions for women where faulty immune tolerance is a likely cause of reproductive dysfunction. This could provide a hitherto unknown mechanism to influence endometrial receptivity for embryo implantation and regulation of female fertility as seen in rodent species.