Biological sex: an understudied factor driving disease susceptibility in pigs

Abstract

Biological sex is a major host factor influencing risk for infectious disease-associated mortality, and chronic inflammatory and metabolic diseases. Research in human and rodent models –has revealed sex differences that exist across organ systems during health and disease that may contribute to sex biases in disease risk. Despite the robust and growing literature on the role of sex as a risk factor in human disease, comparatively little attention has been focused on investigating the role of biological sex in disease susceptibility in agriculturally important animal populations such as the pig. To date, comparisons between sexes have focused on carcass composition, growth rate, and feed efficiency in pigs. However, there is a large gap in the literature regarding the effects of biological sex on other integral aspects of health and disease. The objective of this review is to highlight the available literature reporting sex differences in pig health and biology with an emphasis on sex differences in mortality, immunity, and gastrointestinal (GI) physiology and to address biological sex as a significant biological variable in disease risk and research study design. A basic overview of the biology of sex differences including the major hormonal and genetic/chromosomal mechanisms of sexual differentiation and the developmental periods in which sex differences emerge will be covered. This review will also discuss how production-relevant management and environmental factors (e.g., wean age, castration, stress, and nutrition) interact with biological sex to shape host immune and GI development and function. Perceived gaps in knowledge and areas of future research will also be discussed.

siRNA-mediated reduction of a circulating protein in swine using lipid nanoparticles

“…As sex is an important biological variable, it warrants additional research when developing future gene therapies and genetic tools. Sex differences between female and male swine include an increased inflammatory response to bacterial challenge 76 and superior hemodynamics and reduced cardiac injury during hemorrhage. 77 The blood coagulation analyses, including ROTEM, fibrinogen, and D-dimer measurements, suggest that siPLG is specific for plasminogen, and there were no off-target effects on the gene expression of other coagulation or fibrinolytic factors.…”

Early weaning and biological sex shape long-term immune and metabolic responses in pigs

“…Why EW-F exhibit a heightened immune response remains unknown. Female-biased immune activation has often been ascribed to the impacts of adult gonadal sex hormones 11 . For example, estrogen is well known to exert multifaceted effects on the immune system and contribute to sex differences 17 .…”

“…A critical, yet understudied factors impacting stress responses and disease risk in pigs is biological sex. Biological sex is known to play a significant role in determining the outcome of various infectious diseases across species 11 . In pigs, castrated male pigs have been reported to exhibit higher mortality rates than females, with rates up to 2.5 times higher 12 , 13 .…”