Ebru Gokdere

Psychological stress can affect female reproductive function through behavioral, endocrine, ovarian, and oxidative mechanisms. Antioxidant supplements have therefore attracted attention for their potential to mitigate stress-related reproductive alterations. Coenzyme Q10 (CoQ10) is a lipid-soluble quinone involved in mitochondrial energy metabolism and is widely used as a dietary supplement. However, whether CoQ10 modulates female reproductive responses to repeated psychological stress remains unclear. Although water avoidance stress (WAS) is a well-established psychogenic stress model, its effects on female reproductive outcomes are still not fully defined. In this study, we examined how repeated WAS affects female reproductive outcomes and whether CoQ10 modifies these effects. Twenty-eight regularly cycling female rats were assigned to sham control, WAS, CoQ10, or WAS + CoQ10 groups. WAS was applied for 1 h/day for 10 days, and CoQ10 was administered orally at 100 mg/kg/day. Repeated WAS did not significantly alter sexual incentive motivation parameters, reproductive hormones, corticosterone, total antioxidant capacity (T-AOC), 8-hydroxy-deoxyguanosine (8-OHdG), or mast cell count under the present experimental conditions (all p > 0.05). However, WAS reduced male-directed active investigation time (p = 0.008) and male investigation preference ratio (p = 0.024), increased absolute ovarian and adrenal gland weights (p = 0.035 and p = 0.016, respectively), reduced primordial follicle number (p = 0.030), decreased germinative epithelium thickness (p = 0.017), lowered VEGF histoscore (p = 0.033) regardless of CoQ10 treatment, and reduced corpus luteum angiogenesis in animals not receiving CoQ10 (p = 0.030). CoQ10 reduced total investigation time toward the male (p = 0.032), male investigation preference ratio (p = 0.037), 17-β estradiol (E2) (p = 0.003), testosterone (p = 0.021), and germinative epithelium thickness (p < 0.001) regardless of WAS exposure. CoQ10 also decreased kisspeptin-1 levels under non-stressed conditions (p = 0.010), while increasing corpus luteum angiogenesis under stress conditions (p = 0.003). Overall, repeated WAS produced selective behavioral and ovarian alterations rather than broad reproductive dysfunction. CoQ10 was not associated with a broadly protective or uniformly beneficial profile in this model, and its endocrine, behavioral, and ovarian effects should be interpreted with caution.

Paroxetine, a selective serotonin reuptake inhibitor commonly used to treat various psychiatric disorders, may adversely affect female reproductive function. Although apigenin has been shown to ameliorate reproductive abnormalities and ovarian dysfunction, its effect on paroxetine-induced reproductive toxicity in females remains unclear. Therefore, this study investigated the potential protective effects of apigenin against paroxetine-induced reproductive alterations in female rats. Female rats with regular estrous cycles were randomly assigned to four groups (n = 9 per group): control, apigenin, paroxetine, and paroxetine + apigenin. The rats received saline, apigenin (20 mg/kg), paroxetine (10 mg/kg), or their combination by oral gavage once daily for about 29 consecutive days. Compared with paroxetine treatment alone, apigenin co-administration restored decreased serum anti-Müllerian hormone (AMH) levels, enhanced PAS reactivity in the zona pellucida, reduced ovarian iNOS immunoreactivity, increased follicle and corpus luteum numbers, and increased ovarian VEGF immunoreactivity. However, apigenin administration alone was associated with reduced testosterone levels and alterations in certain ovarian and uterine histological features in female rats. In conclusion, the findings suggest that apigenin may ameliorate paroxetine-induced reproductive alterations in female rats by modulating AMH levels, follicle and corpus luteum numbers, and ovarian histochemical and molecular parameters.

Vasomotor symptoms, such as hot flashes (HFs), commonly affect women during menopause, leading to a reduced quality of life. The current study evaluates the combined effect of active components Asparagus racemosus (AR) and Trigonella foenum-graecum (TFG) in a single oral formulation (IAT) for alleviating menopausal symptoms in ovariectomized rats. Following bilateral ovariectomy, the animals were randomly assigned to nine groups: (1) Control, (2) Ovariectomy (OVX), (3) OVX+TA1 (TA: Combination of Trigonella and Asparagus; TFG 30 mg/kg + AR 30 mg/kg), (4) OVX+TA2 (TFG 30 mg/kg + AR 15 mg/kg), (5) OVX+TA3 (TFG 15 mg/kg + AR 30 mg/kg), (6) OVX+TA4 (TFG 40 mg/kg + AR 30 mg/kg), (7) OVX+TA5 (TFG 30 mg/kg + AR 40 mg/kg), (8) OVX+IAT1 (IAT: Integrated Asparagus and Trigonella; TFG+AR integrated extract, 30 mg/kg), and (9) OVX+IAT2 (TFG+AR integrated extract, 60 mg/kg). On the 8th day of treatment, tail and skin temperatures were recorded every 30 min for 24 h. Ovariectomized rats exhibited menopausal symptoms, such as hormonal imbalances and elevated skin temperature. Administration of AR, TFG, and IAT significantly decreased serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and cortisol while increasing estradiol, progesterone, and dopamine (p < 0.0001), effectively alleviating hot flash-like symptoms. Additionally, they mitigated ovariectomy-induced oxidative stress by lowering malondialdehyde (MDA) levels and restoring antioxidant enzyme activity. Ovariectomized rats exhibited increased expression of a proto-oncogene (c-FOS), gonadotropin-releasing hormone (GnRH), Kisspeptin, Neurokinin B (NKB), and Transient receptor potential vanilloid 1 (TRPV1), along with reduced expressing brain-derived neurotrophic factor (BDNF) levels, which were reversed by treatment, especially with the IAT2 combination. The AR and TFG combination, particularly in IAT formulations, showed strong potential in alleviating menopausal symptoms in ovariectomized rats. These findings suggest that the combination of AR and TFG extracts could be a natural alternative for managing postmenopausal symptoms by restoring reproductive hormone levels, regulating lipid profiles, and enhancing antioxidant defense systems.