• Inca H R Hundscheid, Schellekens Dirk H S M DHSM Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht,, Joep Grootjans, Derikx Joep P M JPM Pediatric Surgical Center of Amsterdam, Emma Children's Hospital AMC/VUMC, Amsterdam, The Netherlands., Wim A Buurman, Dejong Cornelis H C CHC Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The, and Kaatje Lenaerts.
• Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands.
• Ann. Surg. 2020 Dec 1; 272 (6): 1070-1079.

Background And ObjectiveSex differences in responses to intestinal ischemia-reperfusion (IR) have been recognized in animal studies. We aimed to investigate sexual dimorphism in human small intestinal mucosal responses to IR.MethodsIn 16 patients (8 men and 8 women) undergoing pancreaticoduodenectomy, an isolated part of jejunum was subjected to IR. In each patient, intestinal tissue and blood was collected directly after 45 minutes of ischemia without reperfusion (45I-0R), after 30 minutes of reperfusion (45I-30R), and after 120 minutes of reperfusion (45I-120R), as well as a control sample not exposed to IR, to assess epithelial damage, unfolded protein response (UPR) activation, and inflammation.ResultsMore extensive intestinal epithelial damage was observed in males compared to females. Intestinal fatty acid binding protein (I-FABP) arteriovenous (V-A) concentrations differences were significantly higher in males compared to females at 45I-0R (159.0 [41.0-570.5] ng/mL vs 46.9 [0.3-149.9] ng/mL). Male intestine showed significantly higher levels of UPR activation than female intestine, as well as higher number of apoptotic Paneth cells per crypt at 45I-30R (16.4% [7.1-32.1] vs 10.6% [0.0-25.4]). The inflammatory response in male intestine was significantly higher compared to females, with a higher influx of neutrophils per villus at 45I-30R (4.9 [3.1-12.0] vs 3.3 [0.2-4.5]) and a higher gene expression of TNF-α and IL-10 at 45I-120R.ConclusionThe human female small intestine seems less susceptible to IR-induced tissue injury than the male small intestine. Recognition of such differences could lead to the development of novel therapeutic strategies to reduce IR-associated morbidity and mortality.

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