The molecular tug of war between immunity and fertility: Emergence of conserved signaling pathways and regulatory mechanisms

Abstract

Reproduction and immunity are energy intensive, intimately linked processes in most organisms. In women, pregnancy is associated with widespread immunological adaptations that alter immunity to many diseases, whereas, immune dysfunction has emerged as a major cause for infertility in both men and women. Deciphering the molecular bases of this dynamic association is inherently challenging in mammals. This relationship has been traditionally studied in fast-living, invertebrate species, often in the context of resource allocation between life history traits. More recently, these studies have advanced our understanding of the mechanistic underpinnings of the immunityfertility dialogue. Here, we review the molecular connections between reproduction and immunity from the perspective of human pregnancy to mechanistic discoveries in laboratory organisms. We focus particularly on recent invertebrate studies identifying conserved signaling pathways and transcription factors that regulate resource allocation and shape the balance between reproductive status and immune health.

Sexual conflict drives micro- and macroevolution of sexual dimorphism in immunity

“…Sexual selection can result in increased male harm to females during mating (22,29,32), either through direct injury or infection with pathogens, and this should in theory favour increased female investment in immunity when female lifetime reproductive success is elevated by increased longevity (16,18,23,26). Here, we provide a suite of experimental and comparative data collectively showing that sex-differences in immunity can be modulated by sexual conflict in a species where costs of mating are conspicuous.…”

“…Investment in immune defence is costly. These costs have most often been observed as reductions in fecundity, effectively translating into reproduction-survival trade-offs in the presence of pathogens (9,16,21,22). In polygamous species where sexual selection on males is intense, females are predicted to gain more than males from investing in survival and longevity at the cost of current reproduction and mating effort (3,9,23), and should thus invest more in immunity than males (but see: (2,18,23,24)).…”

Transcriptomic evidence for a trade-off between germline proliferation and immunity inDrosophila

“…A major physiological system that might underpin trade-offs between reproduction and survival is the immune system (Sheldon and Verhulst 1996;Lochmiller and Deerenberg 2000;Fedorka et al 2004;Graham et al 2011;Schwenke et al 2016;Naim et al 2020). Indeed, a large body of work has documented trade-offs between reproductive processes (including mating) and immune function, both in invertebrates and vertebrates (Sorci et al 1996;Norris and Evans 2000;Adamo et al 2001;McKean and Nunney 2001;Fedorka et al 2004;Greenman et al 2005;Schmid-Hempel 2005;Williams 2005;French et al 2007;Martin et al 2008;Miyata et al 2008;Speakman 2008;Schwenke et al 2016;Nystrand and Dowling 2020;Pick et al 2020).…”

“…Despite this evidence, many fundamental aspects of reproduction-immunity trade-offs remain poorly understood (Rolff and Siva-Jothy 2002;Flatt et al 2005;Harshman and Zera 2007;Flatt et al 2008a;Speakman 2008;Schwenke et al 2016;Schwenke and Lazzaro 2017;Fabian et al 2018;Garschall and Flatt 2018;Naim et al 2020;Gupta et al 2021). This not only includes specific questions about underlying molecular or physiological mechanisms, but also more basic questions, including the issue of whether such trade-offs are symmetrical or not.…”

“… 2016 ; Naim et al. 2020 ). Indeed, a large body of work has documented trade‐offs between reproductive processes (including mating) and immune function, both in invertebrates and vertebrates (Sorci et al.…”