Influence of semen on inflammatory modulators of embryo implantation

Abstract

Insemination transmits to the female reproductive tract constituents of seminal plasma that target uterine epithelial cells to activate a cascade of inflammatory and immunological changes. Experiments in rodents show seminal factor signalling acts to 'condition' the female immune response to tolerate the conceptus, and to organise molecular and cellular changes in the endometrium to facilitate embryo development and implantation. The active factors in seminal plasma are identified as members of the transforming growth factor-g family, with the relative balance of active moieties influencing the precise character of the female tract response. Experiments in rodents show that disruption of seminal plasma priming causes foetal growth retardation and changes in placental structure, with long-term consequences for the growth of the neonate. Recent studies indicate a similar physiological function and molecular basis for seminal plasma actions in the pig. In gilts, seminal plasma elicits an endometrial response characterised by recruitment of inflammatory leukocytes and induction of several pro-inflammatory cytokines and cyclo-oxygenase-2. The consequences are evident throughout the pre-implantation period of early pregnancy with altered leukocyte populations and cytokine parameters seen for at least 9 days. Exposure to semen also alters the dynamics in pre-implantation embryo development with an increase in the number of embryos and in their viability. Furthermore seminal plasma influences the temporal kinetics of ovulation, corpus luteum development and steroid production in the ovary. Dissecting the actions of seminal plasma may facilitate development of strategies to ensure maximal fertility and reduce embryo mortality in the pig.

Blastocyst-Bearing Sows Display a Dominant Anti-Inflammatory Cytokine Profile Compared to Cyclic Sows at Day 6 of the Cycle

“…It is well known that under physiological conditions in pigs, AI components, including seminal plasma (SP) and spermatozoa, provoke a rapid uterine inflammatory response that induces changes at the cellular and molecular levels [5][6][7][8]. This immediate endometrial inflammatory reaction post-insemination is transient and quickly gives rise to an anti-inflammatory immunotolerant environment that favors embryo survival and proper progression of pregnancy [8][9][10][11][12]. Additionally, the female reproductive tract is able to detect embryo presence prior to implantation and to accordingly modify its immune response [13,14] towards successful implantation [15].…”

Intrauterine Infusion of TGF-β1 Prior to Insemination, Alike Seminal Plasma, Influences Endometrial Cytokine Responses but Does Not Impact the Timing of the Progression of Pre-Implantation Pig Embryo Development

“…It is known that the TGF-β cytokine family plays a major role in the immunomodulatory effects of SP on the maternal genital tract that lead to a preimplantation immunotolerant environment, which is crucial for the establishment of pregnancy [ 56 ]. Moreover, it has been reported that exogenous TGF-β enhances human embryo development in vitro by increasing the number of blastomeres and promoting blastocyst proliferation [ 57 ].…”

Male Seminal Relaxin Contributes to Induction of the Post-mating Cytokine Response in the Female Mouse Uterus

“…It has been shown that seminal plasma per-se , and in particular the TGFß component of this, are important for the recruitment of leukocytes to the uterus and their involvement in the development of immune tolerance to potential paternal alloantigens expressed by the fetus (Robertson et al, 2006 ; Robertson, 2007 ). Some of these experiments made use of relatively gross manipulations of seminal plasma, for example, mating with animals which had had their seminal vesicles surgically removed (Johansson et al, 2004 ).…”

“…There is growing evidence to suggest that during copulation, besides spermatozoa, seminal plasma also delivers a range of signaling molecules into the female tract (Robertson et al, 2006 ; Robertson, 2007 ; Bromfield, 2014 ). One of the most important of these is TGFβ (Sharkey et al, 2012a ), though other molecules, including prostaglandins are likely to be involved.…”