Rat Oestrous Cycle Research Articles

Effects of troxerutin on pentylenetetrazol-induced convulsions during different stages of the estrus cycle in female rats

Effects of troxerutin on pentylenetetrazol-induced convulsions during different stages of the estrus cycle in female rats

Fertility and teratogenic study of the aqueous extract of Hibiscus sabdariffa L. in female Sprague Dawley rats

Hibiscus sabdariffa (roselle) has long been gaining attention in phytotherapy research due to its medicinal properties. Despite its benefits, there is very scarce information available on the reproductive toxicity of this plant. The aqueous extract of H. sabdariffa (AEHS) was tested in the present study to investigate its potential effects on fertility and teratogenicity in 40 female Sprague Dawley rats. AESH treatment was administered orally by gavage at four different dosages: 250, 500 and 1000 mg/kg/day or distilled water (control). Treatment began from pre-mating and continued through mating up to the 19th day of pregnancy periods. Throughout this study, the reproductive parameters were evaluated until the day of sacrifice (day 20th of pregnancy). Results obtained revealed no significant differences in general physical health, behaviours and maternal body weights throughout the treatment period. Furthermore, the mean length of the oestrous cycle was not statistically affected, even though a few rats displayed irregular cycles. In addition, there was no statistical significance in the mating and pregnancy indices, number of corpora lutea and implantation sites, percentages of pre-implantation loss and postimplantation death and reproductive organ weights. Foetal parameters such as the number of live foetuses, sex ratio and body weight were also not statistically affected by AESH. Ultimately, there were no signs of teratogenicity observed since none of the foetuses exhibited congenital malformations. In conclusion, these findings imply that the oral administration of AEHS up to 1000 mg/kg/day did not pose any significant toxicity on the fertility and teratogenicity but slightly affected the oestrous cycle in rats.

Sleep and local field potential effect of the D2 receptor agonist bromocriptine during the estrus cycle and postpartum period in female rats

BackgroundPituitary lactotrophs are under tonic dopaminergic inhibitory control and bromocriptine treatment blocks prolactin secretion. MethodsSleep and local field potential were addressed for 72 h after bromocriptine treatments applied during the different stages of the estrus cycle and for 24 h in the early- and middle postpartum period characterized by spontaneously different dynamics of prolactin release in female rats. ResultsSleep changes showed strong dependency on the estrus cycle phase of the drug application. Strongest increase of wakefulness and reduction of slow wave sleep- and rapid eye movements sleep appeared during diestrus-proestrus and middle postpartum treatments.Stronger sleep-wake effects appeared in the dark phase in case of the estrus cycle treatments, but in the light phase in postpartum treatments. Slow wave sleep and REM sleep loss in case of estrus cycle treatments was not compensated at all and sleep loss seen in the first day post-injection was gained further later. In opposition, slow wave sleep loss in the light phase after bromocriptine injections showed compensation in the postpartum period treatments.Bromocriptine treatments resulted in a depression of local field potential delta power during slow wave sleep while an enhancement in beta and gamma power during wakefulness regardless of the treatment timing. ConclusionsThese results can be explained by the interplay of dopamine D2 receptor agonism, lack of prolactin release and the spontaneous homeostatic sleep drive being altered in the different stages of the estrus cycle and the postpartum period.

Sleep- and sleep deprivation-related changes of vertex auditory evoked potentials during the estrus cycle in female rats

The estrus cycle in female rodents has been shown to affect a variety of physiological functions. However, little is known about its presumably thorough effect on auditory processing during the sleep–wake cycle and sleep deprivation. Vertex auditory evoked potentials (vAEPs) were evoked by single click tone stimulation and recorded during different stages of the estrus cycle and sleep deprivation performed in metestrus and proestrus in female rats. vAEPs showed a strong sleep-dependency, with the largest amplitudes present during slow wave sleep while the smallest ones during wakefulness. Higher amplitudes and longer latencies were seen in the light phase during all vigilance stages. The largest amplitudes were found during proestrus (light phase) while the shortest latencies were seen during estrus (dark phase) compared to the 2nd day diestrus baseline. High-amplitude responses without latency changes were also seen during metestrus with increased homeostatic sleep drive. More intense and faster processing of auditory information during proestrus and estrus suggesting a more effective perception of relevant environmental cues presumably in preparation for sexual receptivity. A 4-h sleep deprivation resulted in more pronounced sleep recovery in metestrus compared to proestrus without difference in delta power replacement suggesting a better tolerance of sleep deprivation in proestrus. Sleep deprivation decreased neuronal excitability and responsiveness in a similar manner both during metestrus and proestrus, suggesting that the negative consequences of sleep deprivation on auditory processing may have a limited correlation with the estrus cycle stage.

Smooth muscle electromyography for detecting major alterations in the estrus cycle in rats.

Determining the female animal cycle is crucial in preclinical studies and animal husbandry. Changes in hormone levels during the cycle affect physiological responses, including altered contractility of the visceral smooth muscle. The study aimed to identify estrus and anestrus using smooth muscle electromyographic (SMEMG) measurements, in vivo fluorescent imaging (IVIS) and in vitro organ contractility of the uterus and cecum. The study involved sexually mature female Sprague-Dawley rats, aged 10-12 weeks. The rats received a daily injection of cetrorelix acetate solution for 7 days, while another group served as the control. The animals were subjected to gastrointestinal and myometrial SMEMG. The change in αvβ3 integrin activity was measured with IVIS in the abdominal cavity. Contractility studies were performed in isolated organ baths using dissected uterus and cecum samples. Plasma samples were collected for hormone level measurements. A 3-fold increase in spontaneous contraction activity was detected in SMEMG measurements, while a significant decrease in αvβ3 integrin was measured in the IVIS imaging procedure. Cetrorelix reduced the level of LH and the progesterone / estradiol ratio, increased the spontaneous activity of the cecum rings, and enhanced KCl-evoked contractions in the uterus. We found a significant change in the rate of SMEMG signals, indicating simultaneous increases in the contraction of the cecum and the non-pregnant uterus, as evidenced by isolated organ bath results. Fluorescence imaging showed high levels of uterine αvβ3 integrin during the proestrus-estrus phase, but inhibiting the sexual cycle reduced fluorescence activity. Based on the results, the SMEMG and IVIS imaging methods are suitable for detecting estrus phase alterations in rats.

Folic acid supplementation and its effects on the oestrus cycle of rats.

Objective: To study the effects of long-term supplemental dose of Folic acid on the oestrous cycle of female Sprague Dawley rats. Study Design: Laboratory-based Experimental study. Setting: Department of Anatomy, CMH Multan Institute of Medical Sciences in Pakistan conducted this research. Period: September 2020 to September 2021. Material & Methods: In this study, 60 female Sprague Dawley rats were used and divided into two groups. The animals of control group A were given distilled water (1ml/100g) by oral gavage daily for four weeks. Folic acid was administered orally to the experimental group B once per day at a dosage of 0.2mg/kg of body weight, diluted in 100 grams of pure distilled water. A vaginal smear was taken every day between 11 am and 12 pm daily for four weeks and the slides were stained with Papanicolaou's stain. SPSS version 26 was used for data entry and analysis. Results: In experimental group B, the animals had an abnormal oestrus cycle. A statistically significant p-value of 0.000 was obtained after comparison between the groups. Conclusion: The current study showed that long-term supplemental dose of Folic Acid leads to prolongation of oestrous cycle of Sprague Dawley rats.

Effects of betaine on pentylenetetrazol-induced convulsions during estrus cycle in rat

Effects of betaine on pentylenetetrazol-induced convulsions during estrus cycle in rat

GHB toxicokinetics and renal monocarboxylate transporter expression are influenced by the estrus cycle in rats

BackgroundThe illicit use and abuse of gamma-hydroxybutyric acid (GHB) occurs due to its sedative/hypnotic and euphoric effects. Currently, there are no clinically available therapies to treat GHB overdose, and care focuses on symptom treatment until the drug is eliminated from the body. Proton- and sodium-dependent monocarboxylate transporters (MCTs (SLC16A) and SMCTs (SLC5A)) transport and mediate the renal clearance and distribution of GHB. Previously, it has been shown that MCT expression is regulated by sex hormones in the liver, skeletal muscle and Sertoli cells. The focus of the current study is to evaluate GHB toxicokinetics and renal monocarboxylate transporter expression over the estrus cycle in females, and in the absence of male and female sex hormones.MethodsGHB toxicokinetics and renal transporter expression of MCT1, SMCT1 and CD147 were evaluated in females over the estrus cycle, and in ovariectomized (OVX) female, male and castrated (CST) male rats. GHB was administered iv bolus (600 and 1000 mg/kg) and plasma and urine samples were collected for six hours post-dose. GHB concentrations were quantified using a validated LC/MS/MS assay. Transporter mRNA and protein expression was quantified by qPCR and Western Blot.ResultsGHB renal clearance and AUC varied between sexes and over the estrus cycle in females with higher renal clearance and a lower AUC in proestrus females as compared to males (intact and CST), and OVX females. We demonstrated that renal MCT1 membrane expression varies over the estrus cycle, with the lowest expression observed in proestrus females, which is consistent with the observed changes in GHB renal clearance.ConclusionsOur results suggest that females may be less susceptible to GHB-induced toxicity due to decreased exposure resulting from increased renal clearance, as a result of decreased renal MCT1 expression.

Endocrine disruptors in Adansonia digitata (Linn) extract induce alteration of female Wistar rats’ oestrous cycle, hormone and lipid profiles

ObjectiveHexane-acetyl acetate (HAAF) and acetyl acetate–methanol fractions (AAMF) but not aqueous methanol (AQMF) and aqueous fractions (AQF) of Adansonia digitata Linn root bark induce reproductive effects in female Wistar rats. The current study investigated the exclusive components of HAAF, AAMF, AQMF, and AQF of Adansonia digitata Linn root bark and the effect of AAMF on the female Wistar rat's oestrous cycle progression, and hormone and lipid profiles. MethodologyGas chromatography and mass spectrometry explored the components of HAAF, AAMF, AQMF, and AQF. Mature female Wistar rats with a proven 4–5-days oestrous cycle were synchronised and randomly assigned into three treatment groups of 30 rats each on the day of proestrus. For seven days, rats in the different groups received 0, 150, and 300 mg kg-1 body weights of AAMF, respectively. Six rats were euthanised from each group based on a standard oestrous stage-timed sequence. The oestrous stage, hormone profile (oestrogen, progesterone, progesterone/oestrogen ratio, and FSH) and lipid profile (Total cholesterol-TC, Triglycerols, High-HD and low density-LD lipid cholesterol) of the euthanised rats were determined. Resultstricosene, cyclopentadecanone 2-hydroxy-, oleic acid, and 9,17-octadecadienal, were exclusively found in HAAF and AAMF. The oestrous stage, serum hormone and lipids varied significantly (p < 0.05) between treatment groups. AAMF fraction induced sustained progesterone levels and depleted oestrogen levels, and TC and LDL were inversely related to serum oestrogen levels. DiscussionThe results suggest a depression of oestrogen and sustenance of progesterone-mediated effects, respectively, on GnRH surge. Oleic acid in AAMF may be responsible for its reproductive effects. ConclusionAAMF fraction of A. digitata (L) root bark disrupts the endocrine activity in female Wistar rats. The oleic acid component of the AAMF fraction may be responsible for modulating the activities of reproductive hormones. The authors recommend further studies to ascertain the significance of Adansonia digitata extract's oleic acid in regulating the female reproductive cycle.

Effects of berberine on pentylenetetrazole-induced seizures during estrus cycle in rats

Effects of berberine on pentylenetetrazole-induced seizures during estrus cycle in rats

Effects of a glyphosate-based herbicide on the oestrous cycle of rats

Objective: To determine the effects of a glyphosate-based herbicide on the oestrous cycle of rats. Methods: Fifteen adult Wistar rats were randomly divided into three groups. Group A served as the control group, while groups B and C received 250 and 500 mg/kg of glyphosate-based herbicide orally for five oestrous cycles, respectively. Stages of oestrous cycle, oestrous cycle index, length of cycle, oestrous cycle ratio, serum estradiol and progesterone levels were determined. Results: The proestrus and oestrus stages of the glyphosate-based herbicide groups increased significantly (P&lt;0.05), although proestrus in group C was not significantly different from the control group. There was a significant decrease in the metestrus and diestrus of the glyphosate-based herbicide groups (P&lt;0.05). The oestrous cycle index of the glyphosate-based herbicide treated groups was altered; this was characterized by an increase in the oestrous index and a decrease in the metestrus and diestrus indexes. The proestrus index of group B increased, while that of group C decreased. The length of the cycle of the glyphosate-based herbicide groups significantly decreased from the 1st and 3rd week till the end of the study in groups B and C, respectively (P&lt;0.05). There was a significant increase in the oestrous cycle ratio of the glyphosate-based herbicide groups compared to the control group (P&lt;0.05). Though the estradiol and progesterone levels of the glyphosate-based herbicide groups increased and decreased, respectively, they were not significantly different from the control group. Conclusions: Glyphosate-based herbicide at the doses of 250 and 500 mg/kg can alter the pattern of the oestrous cycle in rats.

Double perinatal stress reduces the sexual response of adult female Wistar rats.

Early-life stress affects physiological development and produces changes in various aspects of emotional behavior. We sought to examine the effects of double perinatal stress (DPS)-a combination of prenatal systemic hypoxic-ischemic (HI) insults and repeated early maternal separation-on the estrus cycle and sexual behavior of adult rats. HI was induced by clamping the uterine arteries of pregnant rats for 45minutes on the 18th day of gestation (HI group). Sham control animals received laparotomy and anesthesia only. Pups were born at term. Maternal separation was performed from postnatal day 1 (P1) (P0 = day of birth) to P15. At P90, the sexual response of females in estrus was evaluated. Statistical analysis was performed using 2-way analysis of variance followed by Tukey's test. We considered the estrous cycle and sexual behavior of female rats submitted to DPS, as well as the influence of female behavior on the sexual response of male rats. Rats submitted to DPS showed a reduction in the lordosis quotient and in the lordosis rate, suggesting a reduction in female sexual receptivity. DPS female rats showed a reduction in the number of hops and darts and in the genital exploration time rate, suggesting a reduction in sexual proceptivity. In addition, males that interacted with DPS females showed a reduction in the number of ejaculations and in copulatory efficiency. Developing a deeper understanding of perinatal factors that affect adult female sexual response will allow for more effective interventions to prevent and treat such changes. On the other hand, the analysis of the sexual response allows assessing the quality of life and the general state of health. The development of animal models to investigate the environmental factors that interfere in the female sexual response may allow researchers to propose and test new therapeutic strategies. On the other hand, care must be exercised when interpreting animal data and extrapolating these results to estimate the possible effects of perinatal stressors on the human sexual response. Our results revealed that females subjected to DPS showed long-term effects on sexual behavior. In conclusion, managing stressors in prenatal life and early postnatal life can prevent problems in adult sexual life and improve overall health.

Effects of Ginsenosides on Pentylenetetrazol-Induced Convulsions during Estrus Cycle in Rat.

Ginseng is known as the king of all herbs in terms of antioxidant and anti-inflammatory activities and recently has become more involved in the treatment of neurological diseases. In this regard, this study aimed to determine the effects of Ginsenosides on pentylenetetrazol-induced epilepsy during the estrus cycle. For this purpose, 30 rats were randomly divided into five groups, namely control (saline), valproic acid (VPA, 75 mg/kg), Ginsenosides (50 mg/kg), Ginsenosides (100 mg/kg), and Ginsenosides (150 mg/kg) with four subgroups (proestrus, estrus, metestrus, and diestrus). Subsequently, the initiation time of myoclonic seizures (ITMS), initiation time of tonic-clonic seizures (ITTS), and seizure duration (SD) were determined. According to the results, ITMS and ITTS significantly increased in the VPA-treated group (P<0.05). Ginsenosides (100 and 150 mg/kg) administration significantly increased ITMS and ITTS (P<0.05). Moreover, the ITMS and ITTS in Ginsenosides-treated rats were significantly higher in luteal phases, compared to the follicular phase (P<0.05). In addition, pretreatment with VPA significantly decreased SD, compared to the control group (P<0.05). A significant decrease in SD was observed in the rats pretreated with ginsenosides (100 and 150 mg/kg) (P<0.05). Seizure duration significantly decreased in animals that received Ginsenosides in luteal phases, compared to the follicular phase (P<0.05). These results suggested that Ginsenosides have anticonvulsant effects that are more prominent during the luteal phase than the follicular phase.

Characterization, Phytochemical Screening of Phyllanthus emblica L. Fruit Nanoherbal and Determination of the Estrus Cycle of Female Rats

One of a plant that is thought to have quite high antioxidant activity is kemloko (Phyllanthus emblica L.). This plant is a material that is often used by the community as a traditional medicine. This plant in India has been used to treat cancer, diabetes, liver (liver), heart problems and anemia. This biological activity is thought to be caused by the presence of bioactive compounds from secondary metabolites contained therein, especially compounds from the phenolic and flavonoid groups. The short length of the estrus cycle of rats makes them ideal for investigation of changes occurring during the reproductive cycle. The estrus cycle lasts four days and is characterized as: proestrus, estrus, metestrus and diestrus, which may be determined according to the cell types observed in the vaginal smear. Since the collection of vaginal secretion and the use of stained material generally takes some time, the aim of the present work was to provide researchers with some helpful considerations about the determination of the rat estrus cycle phases in a fast and practical way. This study began with macroscopic examination, examination of water content, examination of water-soluble extract levels, examination of ethanol-soluble extracts, examination of total ash content, and also an examination of acid-insoluble ash levels, phytochemical screening of Phyllanthus emblica L. fruit nanoherbal and determination of the estrus cycle of female rats. The results of phytochemical screening showed that the compound of Phyllanthus emblica L. Fruit nanoherbal contained a class of secondary metabolites of alkaloids, flavonoids, tannins, saponins, steroids/triterpenoids, and glycosides. And the estrus cycle of female rats can be determined by observing changes in vaginal epithelial cells.

Modulation of Melatonin Receptors Regulates Reproductive Physiology: The Impact of Agomelatine on the Estrus Cycle, Gestation, Offspring, and Uterine Contractions in Rats

Agomelatine is a pharmaceutical compound that functions as an agonist for melatonin receptors, with a particular affinity for the MT1 and MT2 receptor subtypes. Its mode of action is integral to the regulation of diverse physiological processes, encompassing the orchestration of circadian rhythms, sleep-wake cycles, and mood modulation. In the present study, we delve into the intricate interplay between agomelatine and the modulation of estrus cycles, gestation periods, offspring numbers, and uterine contractions, shedding light on their collective impact on reproductive physiology. Both in vivo and in vitro experiments were performed. Wistar Albino rats, divided into four groups: two non-pregnant groups (D1 and D2) and two pregnant groups (G1 and G2). The D1 and G1 groups served as control groups, while the D2 and G2 groups received chronic agomelatine administration (10 mg/kg). Uterine contractions were assessed in vitro using myometrial strips. Luzindole, a melatonin receptor antagonist, was employed to investigate the pathway mediating agomelatine's effects on uterine contractions. In in vivo studies, chronic agomelatine administration extended the diestrus phase (p&lt;0.05) in non-pregnant rats, prolonged the gestational period (p&lt;0.01), and increased the fetal count (p&lt;0.01) in pregnant rats. Additionally, agomelatine reduced plasma oxytocin and prostoglandin-E levels (p&lt;0.01) during pregnancy. In vitro experiments showed that agomelatine dose-dependently inhibited spontaneous and oxytocin-induced myometrial contractions. Luzindole (2 µM) reverse the agomelatine-induced inhibition of myometrial contractions. These findings suggest that agomelatine holds the potential to modulate diverse reproductive parameters during the gestational period, influencing estrus cycling, gestational progression, offspring development, and the orchestration of uterine contractions.

An Experimental Study- to Evaluate the Effect of Shatapushpa Taila on Estrous Phase of Female Wistar Albino Rats

From early adolescence to menopause, the menstrual cycle affects a woman’s physiological and psychological health for about 35 to 40 years in a normal population. Properly functioning hypothalamo pituitary ovarian axis, receptive endometrium with healthy ovum and sperm are considered to be the essential factors for conception. Acharyas have quoted Rutu, Kshetra, Ambhu and Beeja as Garbha sambhava samagri which is essential for conception where in Beeja can be taken as ovum. Shatapusha is mentioned in Kashyapa samhitha as Artavajanaka, hence an effort to evaluate its effect on estrous phase of female Wistar albino rats is the aim of this study. The selected animal was grouped into four groups with 6 animals each. The animal experiment showed significant increase in estrus phase of the oestrous cycle in rats which is the active phase of mating where the female receives the male.

Ameliorative effect of Withania somnifera against Imidacloprid Induced Alterations in Oestrous Cycle of Female Albino Wistar Rats

Ameliorative effect of Withania somnifera against Imidacloprid Induced Alterations in Oestrous Cycle of Female Albino Wistar Rats

Exploration of the Danggui Buxue Decoction Mechanism Regulating the Balance of ESR and AR in the TP53-AKT Signaling Pathway in the Prevention and Treatment of POF

Objective The purpose of this study was to explore the molecular mechanism of Danggui Buxue Decoction (DBD) intervening premature ovarian failure (POF). Methods The active compounds-targets network, active compounds-POF-targets network, and protein-protein interaction (PPI) network were constructed by a network pharmacology approach: Gene Ontology (GO) function and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis by DAVID 6.8 database. The molecular docking method was used to verify the interaction between core components of DBD and targets. Then, High-Performance Liquid Chromatography (HPLC) analysis was used to determine whether the DBD contained two key components including quercetin and kaempferol. Finally, the estrous cycle, organ index, ELISA, and western blot were used to verify that mechanism of DBD improved POF induced by cyclophosphamide (CTX) in rats. Results Based on the network database including TCMSP, Swiss Target Prediction, DisGeNET, DrugBank, OMIM, and Malacard, we built the active compounds-targets network and active compounds-POF-targets network. We found that 2 core compounds (quercetin and kaempferol) and 5 critical targets (TP53, IL6, ESR1, AKT1, and AR) play an important role in the treatment of POF with DBD. The GO and KEGG enrichment analysis showed that the common targets involved a variety of signaling pathways, including the reactive oxygen species metabolic process, release of Cytochrome C from mitochondria and apoptotic signaling pathway, p53 signaling pathway, the PI3K-Akt signaling pathway, and the estrogen signaling pathway. The molecular docking showed that quercetin, kaempferol, and 5 critical targets had good results regarding the binding energy. Chromatography showed that DBD contained quercetin and kaempferol compounds, which was consistent with the database prediction results. Based on the above results, we found that the process of DBD interfering POF is closely related to the balance of ESR and AR in TP53-AKT signaling pathway and verified animal experiments. In animal experiments, we have shown that DBD and its active compounds can effectively improve estrus cycle of POF rats, inhibit serum levels of FSH and LH, protein expression levels of Cytochrome C, BAX, p53, and IL6, and promote ovary index, uterine index, serum levels of E2 and AMH, and protein expression levels of AKT1, ESR1, AR, and BCL2. Conclusions DBD and its active components could treat POF by regulating the balance of ESR and AR in TP53-AKT signaling pathway.

The Effects of Calina Papaya Leaf Ethanol Extract On Estrus Cycle And Uterus Morphology of Wistar Rats

Calina papaya leaf is an Indonesian papaya plant type that has the potential to be used as a medicinal plant. Phytochemical compounds found in papaya leaves act as antifertility agents. The research aimed to study the antifertility effect of Calina papaya leaf ethanol extract on estrus cycle and uterine morphology of wistar rats. The experiment lasted 30 days and involved 25 female wistar rats. The treatment consisted of 5 groups, namely K (distilled water), K+ (contraceptive pill), P1 (Calina papaya leaf ethanol extract 200mg/KgBW), P2 (Calina papaya leaf ethanol extract 300mg/KgBW), and P3 (Calina papaya leaf ethanol extract 400mg/KgBW). The parameters of estrus cycle consisted of estrus cycle phase, total cycle and estrus cycle ratio. Uterus morphological parameters consist of wall thickness of the endometrium, myometrium, and perimetrium. The estrus cycle examination was carried out every day using the vaginal smear method (Giemsa 5%). On the 31st day, surgery was performed and the uterus was taken for histological observation using the paraffin method (HE staining). Data were analyzed using One Way ANOVA with further Duncan’s test. The results showed that a dose of 400 mg/KgBW could affect the estrus cycle with accelerate the estrus phase and increase the estrus cycle ratio compared to the control (P0.05). There was a decrease in endometrium and myometrium wall thickness at a dose of 400 mg/KgBW compared to the control (P0.05). The conclusion of the study is that the ethanol extract of Calina papaya leaves at a dose of 400 mg/KgBW has the potential to be a natural antifertility agent on female wistar rats.

Activated Human Umbilical Cord Blood Platelet-Rich Plasma Enhances the Beneficial Effects of Human Umbilical Cord Mesenchymal Stem Cells in Chemotherapy-Induced POF Rats.

Saving the ovarian function of premature ovarian failure (POF) patients undergoing chemotherapy is an important problem in the field of reproductive medicine. At present, human umbilical cord mesenchymal stem cells (HucMSCs) have been used in the treatment of POF, but the effect is still not optimal. The purpose of this study was to determine whether human umbilical cord blood platelet-rich plasma (ucPRP) enhances the beneficial effects of HucMSCs in the treatment of POF. First, we observed the effects of changes in the biological activity of ucPRP on HucMSCs in vitro. Subsequently, we tracked the distribution and function of the HucMSCs in POF rats, and the rats' estrus cycle and serum sex hormones, follicular development, ovarian angiogenesis, ovarian granulosa cell proliferation, and apoptosis were assessed. The results of the study showed that the addition of ucPRP in vitro accelerates proliferation and reduces apoptosis of the HucMSCs while upregulating the stemness gene of the HucMSCs. The combined transplantation of HucMSCs and ucPRP resulted in more stem cells being retained in the ovaries of POF rats, the estrus cycle of the POF rats being restored, the levels of serum E2, AMH, and FSH improving, and damaged follicles beginning to grow. Finally, we confirmed that the potential mechanism of the combination of HucMSCs and ucPRP to rescue the ovarian function of POF rats is to promote ovarian angiogenesis and to promote the proliferation and reduce the apoptosis of ovarian granulosa cells. The upregulation of AMH and FHSR expression and the downregulation of caspase-3 expression in granulosa cells are potential mechanisms for the recovery of ovarian function. Our research results suggest that the combined application of HucMSCs and ucPRP is a safe and efficient transplantation program for the treatment of POF, thus providing a reliable experimental basis for the clinical application of stem cell therapy in POF.