The innate immune system senses pathogens by pattern recognition receptors (PRR) that signal to induce effector cytokines, such as type I interferons (IFNs). We characterized IFNε as a type I IFN because it signaled via the Ifnar1 and Ifnar2 receptors to induce IFN-regulated genes. In contrast to other type I IFNs, IFNε was not induced by known PRR pathways, but was instead constitutively expressed by epithelial cells of the female reproductive tract (FRT) and hormonally regulated. Ifnε-deficient mice had increased susceptibility to infection of the FRT by common sexually transmitted infections (STIs) Herpes Simplex Virus (HSV)-2 and Chlamydia muridarum. IFNε is thus a potent anti-pathogen and immunoregulatory cytokine that may be important in combating STIs which represent a major global health and socioeconomic burden.
Paternal characteristics and exposures influence physiology and disease risks in progeny, but the mechanisms are mostly unknown. Seminal fluid, which affects female reproductive tract gene expression as well as sperm survival and integrity, provides one potential pathway. We evaluated in mice the consequences for offspring of ablating the plasma fraction of seminal fluid by surgical excision of the seminal vesicle gland. Conception was substantially impaired and, when pregnancy did occur, placental hypertrophy was evident in late gestation. After birth, the growth trajectory and metabolic parameters of progeny were altered, most profoundly in males, which exhibited obesity, distorted metabolic hormones, reduced glucose tolerance, and hypertension. Altered offspring phenotype was partly attributable to sperm damage and partly to an effect of seminal fluid deficiency on the female tract, because increased adiposity was also evident in adult male progeny when normal two-cell embryos were transferred to females mated with seminal vesicle-excised males. Moreover, embryos developed in female tracts not exposed to seminal plasma were abnormal from the early cleavage stages, but culture in vitro partly alleviated this. Absence of seminal plasma was accompanied by down-regulation of the embryotrophic factors Lif, Csf2, Il6, and Egf and up-regulation of the apoptosis-inducing factor Trail in the oviduct. These findings show that paternal seminal fluid composition affects the growth and health of male offspring, and reveal that its impact on the periconception environment involves not only sperm protection but also indirect effects on preimplantation embryos via oviduct expression of embryotrophic cytokines.T he plasma fraction of seminal fluid contains a complex mix of bioactive proteins and other agents produced by male accessory sex organs, which act after intromission to maximize the chances of successful conception by promoting sperm survival and functional competence (1). Seminal plasma can also affect reproductive events independent of sperm. Seminal fluid regulation of female reproductive physiology is well-known in insects, where effects on female reproductive organs, immune system, and behavioral responses promote fertilization and transmission of the male germ line (2). Rodent, porcine, and human studies show that seminal fluid also exerts a substantial influence on female reproductive tract physiology in vertebrates (3, 4). TGF-β and E-series prostaglandins, produced in the seminal vesicle and other male accessory glands, are major male-female signaling agents in mammalian seminal fluid (5). These factors induce the female reproductive tract to synthesize cytokines and chemokines that in turn influence the immune response to facilitate tolerance of male gametes and the conceptus (3).The periconception phase is a time of developmental plasticity, when the embryo is highly responsive to cues affecting later fetal and postnatal development (6). Greater susceptibility of adult offspring to metabolic disease can res...
Seminal 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 to selectively target and eliminate excess sperm. Other signals stimulate ovulation, induce an altered transcriptional program in female tract tissues that modulates embryo developmental programming, and initiate 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 choiceˮ 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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.