Impact of a non-invasive oestrous synchronisation protocol on sexual behaviour in Sprague-Dawley rats
Geomar Seijas-Pedroza1,2, Alfonso Gómez Del Val1,3,4, Gregers Wegener5,6
1Aarhus University, Department of Biomedicine/Pharmacology/Faculty of Health, 8000 Midtjylland, Aarhus C, Denmark.
Background:
Female Sexual Dysfunction (FSD) is prevalent worldwide; however, current preclinical models often rely on invasive ovariectomy and supra-physiological hormone administration, limiting translational relevance.
Aim:
Our hypothesis is that a non-invasive protocol using a prostaglandin F2α analogue (cloprostenol) will effectively synchronise the oestrous cycle of female rats to study its effects on sexual motivation and behaviour, with potential implications for FSD research.
Methods:
Twelve-week-old intact-untrained female Sprague-Dawley rats received intramuscular-subcutaneously (SQ) injections of cloprostenol at 75, 125, or 250 μg/kg on days 0 and 3, respectively, followed by progesterone (1 mg/kg) SQ on day 4. Vaginal cytology confirmed the cycle synchronisation. Sexual motivation was assessed. Plasma/vaginal hormonal levels (oestradiol and follicle-stimulating hormone/FSH levels) were measured by enzyme-linked immunosorbent assay/ELISA. Vaginal oestradiol levels were determined in unsynchronised rats (n = 28). Open-field and forced swim tests evaluated locomotion, anxiety, and depression-like behaviours.
Methods Outcomes:
Sexual behaviour was assessed using an incentive and encounter profile test. The latter categorised behaviour as paracopulatory/executive. Open field and forced swim test evaluated locomotion, anxiety, and depression-like behaviours. Plasma hormonal levels (FSH and oestradiol levels) were measured by ELISA; the latter, besides plasma, was also vaginal. All under evaluation of new doses in rodents for their oestrous synchronisation protocol.
Results:
All doses effectively synchronised rats in the proliferative/transitional phase, with hormonal levels within physiological ranges. Behavioural tests at 125 μg/kg cloprostenol showed increased proceptivity, with females exhibiting greater sexual motivation and interest, whereas higher doses were associated with decreased precopulatory behaviours. Although male rats showed increased interest in females during metoestrus or following treatment with 250 μg/kg cloprostenol. No significant differences were observed in anxiety or depression-like behaviours across the doses or oestrous phases.
Clinical Implications:
125 μg/kg cloprostenol results could translate to a higher desire in women of reproductive age, and 250 μg/kg cloprostenol translates to women with less desire to copulate/intercourse, where potential treatment could improve their sexual parameters to help them increase their desire.
Strengths And Limitations:
Most rats synchronised to the proliferative/transitional phase with 125/250 μg/kg cloprostenol, supporting its effectiveness. Future studies should consider oestrous cycle phases when evaluating treatments for FSD in rodents and include rats in the dioestrus phase.
Conclusion:
The non-invasive cloprostenol protocol reliably synchronised the oestrous cycle and modulates sexual motivation in female rats, providing a physiologically relevant model for investigating FSD. This approach minimises surgical interventions and high hormonal doses, thus enhancing the translational potential of future therapeutics.
