Male to female seminal fluid signalling – intersexual war and peace with consequences for offspring health (#120)
The peri-conceptual period when the embryo is formed and implantation occurs, is critical not just for initiating pregnancy but also in setting the trajectory for the health of the child after birth and in later life. Even minor insults to the embryo, or to the female tract environment, are reflected in later morphogenesis of the placenta and its capacity to optimally support fetal growth. The mother’s immune system is intimately engaged with these early events – it acts to exert quality control over the gametes and embryo, to actively suppress rejection of the conceptus, and to facilitate placental invasion and function. In mammals, the male seminal fluid is generally thought to participate in one straightforward way – by providing sperm to fertilise the oocyte. But the male contribution may not be so simple, with emerging evidence for functions of seminal fluid in activating the female immune response, in influencing fertility and in programming offspring health. We have discovered that microRNAs present in sperm may be delivered to cells of the female reproductive tract after coitus, where they alter gene expression and modify tissue function, potentially to increase the chances of pregnancy and influence the course of its progression. Strikingly, several sperm-borne miRNAs have known actions in regulating the immune response, and may influence fertility by modulating the female immune system. Male-female seminal fluid signalling by miRNA potentially provides a completely novel mechanism for regulation of the female reproductive process and influencing female quality control. Pathologies of pregnancy such as implantation failure or recurrent miscarriage may be due to inadequate male-female seminal fluid communication, or over-zealous female quality control. Defining the molecular communication between the male and female at coitus, and its impact on immune decision-making in the peri-conceptual period, will shed new light on infertility and subfertility disorders with an immune aetiology.