Algae-derived bioactives have emerged as promising nutraceuticals due to their ability to modulate key molecular pathways under physiological stress. Arthrospira platensis (Spirulina), a cyanobacterium widely recognized for its antioxidant and anti-inflammatory properties, is proposed as a functional supplement to preserve smooth muscle physiology. Progressive strength training (PST) can induce oxidative stress and disrupt electromechanical coupling in the uterus, potentially impairing female reproductive function. This study investigated whether supplementation with A. platensis prevents PST-induced uterine dysfunction and elucidated the molecular mechanisms involved. Virgin Wistar rats were divided into five groups: sedentary with saline (GS), sedentary with A. platensis (GAP100), adapted control (GC), PST-trained (GT), and PST-trained with A. platensis (GTAP100). An eight-week water-jump PST protocol was applied. Uterine contractile responses were recorded in isolated organ baths after cumulative KCl stimulation, in the absence or presence of pathway-specific inhibitors targeting nitric oxide synthase, cyclooxygenase, NADPH oxidase, or superoxide dismutase. Histological evaluations of uterine and ovarian tissues were also performed. PST increased contractile efficacy and myometrial thickness, associated with oxidative stress and activation of NO, COX, and NADPH oxidase pathways. Supplementation with A. platensis attenuated these alterations by enhancing NO signaling, stimulating relaxant prostanoids, and reducing superoxide production. These protective effects were abolished by inhibitors, confirming mechanistic involvement. Overall, our findings provide molecular evidence that A. platensis supplementation preserves uterine smooth muscle physiology under high-intensity resistance training, supporting its potential as a nutraceutical strategy for female reproductive health.

Background/Objectives: Primary dysmenorrhea (DysP) is a prevalent gynecological condition characterized by painful uterine contractions. However, the underlying mechanism of action of dysmenorrhea has not been fully elucidated. This study aimed to standardize an animal model of dysmenorrhea using diethylstilbestrol and oxytocin to mimic pathophysiological mechanisms in female Wistar rats. Methods: For the induction of dysmenorrhea, diethylstilbestrol (s.c.) and oxytocin (i.p.) were used. Results: The model effectively reproduced hypercontractility and impaired uterine relaxation. The in vivo evaluations demonstrated increased pain responses (DysP group = 119 ± 6.9; control group CG = 3.0 ± 1.0), which were partially attenuated by standard medications (scopolamine/dipyrone and ibuprofen). In vitro assays revealed greater contractile reactivity when compared to that in the control group, in the DysP group, using oxytocin (pEC₅₀ = 3.6 ± 0.2 and E_max = 145.1 ± 8.7; CG (pEC₅₀ = 3.1 ± 0.1 and E_max = 100%); KCl (DysP pEC₅₀ = 2.2 ± 0.1 and E_max = 164 ± 8.0); CG (pEC₅₀ = 1.8 ± 0.1) and PGF_2α (DysP pEC₅₀ = 7.4 ± 0.2 and E_max = 127.3 ± 15.6); CG (pEC₅₀ = 6.2 ± 0.1)), while the relaxation responses to isoprenaline and nifedipine were decreased compared to those in the CG. The model promoted an imbalance in oxidative stress by increasing malondialdehyde (MDA) levels and reducing the total antioxidant capacity (TAC) in the uterine tissue. Conclusions: These findings suggest that the new virgin rat model is capable of replicating key aspects of the clinical features of DysP in humans and offers a valuable tool for studying its pathogenetic mechanisms and testing potential therapeutic agents.