Fertility protective effect of taxifolin in cisplatin-induced ovarian damage.

OBJECTIVE: The aim of our study was to investigate the protective effect of taxifolin on ovarian damage and reproductive dysfunction created by cisplatin administration. MATERIALS AND METHODS: A total of 36 albino Wistar female adult rats were equally divided into 3 groups as cisplatin administered only (CIS), taxifolin+cisplatin (T+C) and healthy control group (HG). Taxifolin 50 mg/kg was administered orally by gavage in the T+C (n=12) group. In the HG (n=12) and CIS (n=12) groups, the same volume of distilled water as a solvent was orally administered. One hour after administration of taxifolin or distilled water, animals in the T+C and CIS groups were injected with cisplatin at a dose of 2.5 mg/kg intraperitoneally. This procedure was repeated once a day for 14 days. Six animals from each group were sacrificed on day 15, and their ovaries were removed for histopathological and biochemical analysis. Ovarian tissue malondialdehyde (MDA), total Glutathione (tGSH), Nuclear Factor-Kappa B (NF-kB), Tumor Necrosis Factor-α (TNF-α), Interleukin 1 beta (IL-1ß), and Interleukin-6 (IL-6) levels were measured. The remaining animals (n=6 in each group) were kept in the laboratory with mature male rats for two months to breed. RESULTS: CIS administration led to an increase in inflammatory molecules and membrane lipid peroxidation products, and decreased the synthesis of antioxidant molecules. Compared to the CIS group, the ovarian tissue MDA, NF-kB, TNF-α, IL-1ß and IL-6 levels were found to be significantly decreased in the T+C group (p<0.001 for all comparisons). On the other hand, the tGSH levels of the T+C group were significantly higher than the CIS group (p<0.001). Milder ovarian necrosis, fibrosis and follicle damage were detected in animals which were given taxifolin. Four out of the six rats (67%) treated with taxifolin gave birth within 27 days. CONCLUSIONS: We demonstrated, for the first time, that taxifolin ameliorates cisplatin-induced ovarian injury by decreasing MDA and proinflammatory cytokines and increasing the antioxidant enzyme. The fact that more than half of the animals receiving taxifolin became pregnant suggests that the cytoprotective effect of taxifolin is strong enough to preserve fertility.

Phytochemical analysis and fertility enhancement effects of aerial parts of Fagonia arabica in male and female rats.

In this study, fertility enhancing effect of ethanol extract of aerial parts of Fagonia arabica was evaluated. 24 female and 12 male virgin Wistar rats (Average wt 150-250g) were selected. Dose was given daily for 23 days in 4 groups of animal. After 23 days, they were cohabitated for mating. Then dosing was continued for further 5 days. On 5th day of mating, sperm counting was done by observing vaginal smear under the microscope which showed fertility enhancement in male. Female were kept separately until delivery. The number of pubs born provided female fertility enhancement as compared to control. Average sperm count in 1 cm2 were counted in group A, B, C and control as 14.000±1.732, 12.000±1.000, 23.333±1.528 and 11.000±1.000 respectively. Number of pubs were counted in Group A, B, C and D as 8.667±2.082, 7.333±1.528, 7.333±1.528 10.000±2.000 and 5.333±0.577 respectively and fertility index was calculated for Group A, B and C as 62.516%, 37.502% and 87.512% respectively. Result showed that the orally administered dose of Fagonia arabica possess highly significant fertility enhancing activity in male and female rats after observing improvement in the sperm count and number of pubs as compared to control.

Assessment of Ferula hermonis Boiss fertility effects in immature female rats supported by quantification of ferutinin via HPLC and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferula hermonis is a small shrub renowned for its aphrodisiac abilities. Middle East herbalists have utilized Ferula hermonis seed and root as an aphrodisiac folk medicine to treat women's frigidity and male erectile and sexual dysfunction. AIM OF THE STUDY: Assessment of follicle-stimulating hormone-like (FSH), luteinizing hormone-like (LH), and estrogenic activities of the methanolic extract (ME) of the roots of Ferula hermonis on female reproductive function. MATERIALS AND METHODS: The methanolic extract was prepared from the root of F. hermonis and studied at dose level 6 mg/kg in immature female rats for FSH-like, LH-like, and estrogenic activities. These activities were determined by analyzing gross anatomical features, relative organ weight, and serum level of FSH, LH, progesterone and estrogen hormones, and histopathological characteristics. Quantification of the main phytoestrogenic component ferutinin carried out by HPLC. In addition, molecular docking for the binding affinity of ferutinin inside active sites of both estrogen receptor alpha (ERα) and FSH receptor (FSHR) was performed to predict the potential role of ferutinin in regulating the female reproductive process. RESULTS: Ferula hermonis (ME) showed potent FSH-like, LH-like activities and moderate estrogenic effect at the dose of 6 mg/kg. The content of ferutinin in F. hermonis was estimated to be 92 ± 1.33 mg/g of the methanolic extract. Molecular docking of ferutinin with ERα and FSHR displayed strong interaction with target proteins. CONCLUSIONS: Based on results, it can be concluded that Ferula hermonis can be considered as a suitable female fertility improving agent.

Phoenix dactylifera L. date tree pollen fertility effects on female rats in relation to its UPLC-MS profile via a biochemometric approach.

Date palm (Phoenix dactylifera L.) is among the most ancient cultivated crops, of special value owing to its fruits high nutritive and economic benefits. Asides, date palm pollen is a high energy material that has been used traditionally used for fertility enhancement. In this study, effects of date palm pollen crude extract and its fractions viz., petroleum ether, methylene chloride, ethyl acetate and n-butanol on the female reproductive system were evaluated for the first time in relation to its metabolite fingerprint. Fertility activity was evaluated in immature female rats by assessing their FSH-, LH- and estrogen- activities. To pinpoint active hormonal agents in crude pollen extract and fractions, UPLC- MS analysis was employed for metabolites profiling, and in correlation to extract/fraction bioassays using multivariate OPLS analysis. Results revealed that both polar n-butanol and non-polar petroleum ether fractions exhibited the strongest activities; with a significant increase in FSH (25.7 mIU/ml in n-butanol group), estradiol (414.7 pg/ml in petroleum ether group) and progesterone levels (122.4 pg/ml in n-butanol group). Correlation between UPLC-MS and fraction bioassays was attempted using multivariate OPLS analysis to reveal for bioactive hits in these fractions. This study provides the first report on the fertility effect of date palm pollen in female rats and in relation to its metabolite fingerprint.

Molecular Mechanism and Anti-Fertility Effect of Plant Complex Sterility Agent on Targeted Gene DPY19L2 in Rats.

BACKGROUND: Damage caused by rats is a serious hazard to the environment and crop irrigation. It not only results in great damage to the ecological environment, but also seriously affects the growth and yield of crops and forests. Controlling damage caused by rats is the primary task for improving the environment and maintaining ecological balance. METHODS: Basing on the related gene DPY19L2 in the maturation and development of seminal vesicles in rats, our study explored the effect of non-toxic and pollution-free plant complex sterility agent on rat fertility. RESULTS: The results showed that the plant complex sterility agent could effectively reduce the genital organ index of male rats, change the sperm morphology, reduce the testosterone content and sperm motility, inhibit the expression of spermatogenesis genes DPY19L2, SPATA16, SUN5, and ZPBP, and achieve the effective sterility control of rat pests. CONCLUSIONS: Plant complex sterility agent with high concentration can effectively target rat sperm gene DPY19L2 and realize effective sterility control of rat pests.

Reproductive Longevity and Aging: Geroscience Approaches to Maintain Long-Term Ovarian Fitness.

Increases in delayed childbearing worldwide have elicited the need for a better understanding of the biological underpinnings and implications of age-related infertility. In women 35 years and older the incidences of infertility, aneuploidy, and birth defects dramatically increase. These outcomes are a result of age-related declines in both ovarian reserve and oocyte quality. In addition to waning reproductive function, the decline in estrogen secretion at menopause contributes to multisystem aging and the initiation of frailty. Both reproductive and hormonal ovarian function are limited by the primordial follicle pool, which is established in utero and declines irreversibly until menopause. Because ovarian function is dependent on the primordial follicle pool, an understanding of the mechanisms that regulate follicular growth and maintenance of the primordial follicle pool is critical for the development of interventions to prolong the reproductive life span. Multiple pathways related to aging and nutrient-sensing converge in the mammalian ovary to regulate quiescence or activation of primordial follicles. The PI3K/PTEN/AKT/FOXO3 and associated TSC/mTOR pathways are central to the regulation of the primordial follicle pool; however, aging-associated systems such as the insulin-like growth factor-1/growth hormone pathway, and transsulfuration/hydrogen sulfide pathways may also play a role. Additionally, sirtuins aid in maintaining developmental metabolic competence and chromosomal integrity of the oocyte. Here we review the pathways that regulate ovarian reserve and oocyte quality, and discuss geroscience interventions that leverage our understanding of these pathways to promote reproductive longevity.

How long does the fertility-enhancing effect of hysterosalpingography with oil-based contrast last?

RESEARCH QUESTION: Does the fertility-enhancing effect of tubal flushing during hysterosalpingography (HSG) with oil-based contrast change over time? DESIGN: This was a secondary analysis of the H2Oil (long-term follow-up) study, a multicentre randomized controlled trial evaluating the effectiveness of oil-based and water-based contrast during HSG. The main outcome was ongoing pregnancy. Cox proportional hazards models for time to ongoing pregnancy were fitted over 3 years of follow-up. RESULTS: Data on 1107 couples were available; 550 couples had oil-based contrast and 557 water-based contrast at HSG. Ongoing pregnancy rates after 3 years were 77% and 71%, respectively. Median follow-up was 9-10 months (5th-95th percentile: <1 to 36). The hazard ratio for ongoing pregnancy for oil versus water over 3 years of follow-up was 1.26 (95% confidence interval [CI] 1.10-1.45). The scaled Schoenfeld residual plots showed a decrease in hazard ratio that was linear with log-transformed time. After including an interaction with log-transformed time, the hazard ratio immediately after HSG was 1.71 (95% CI 1.27-2.31) and reduced to no effect (hazard ratio of 1) at approximately 2 years. There was no evidence for a change in hazard ratio over time in a subgroup of women who experienced pain during HSG. CONCLUSIONS: The hazard ratio for ongoing pregnancy of oil-based versus water-based contrast was 1.71 immediately after HSG, gradually decreasing and plateauing towards a hazard ratio of 1 (indicating no effect) after approximately 2 years. This supports the hypothesis that oil-based contrast might dislodge debris or mucus plugs from the Fallopian tubes, but this has yet to be definitively proved.

Endocrine approach in the treatment of obesity: Is there any space for the adiponectin action?

Adiponectin is a hormone secreted by adipose tissue, exerting many positive effects in the human body. Its action has been widely studied, placing it into the metabolic health beneficial products of the adipose tissue. Nevertheless, adiponectin has been shown to exert some extra beneficial non metabolic actions, as well. Adiponectin levels can be related to reduced incidence of cancer in obese patients. Moreover, adiponectin has been shown to be implicated in the positive fertility outcomes of women. Some new studies have also indicated that adiponectin has a potential effect in the control of appetite, which raises a question, whether adiponectin could be accredited to be useful in the endocrine evaluation of obesity. Could these additional non-metabolic actions prove its helpfulness?

Continuous treatment with cisplatin induces the oocyte death of primordial follicles without activation.

Chemotherapy directly or indirectly affects organs in a short-term or continuous manner. Endocrine organs are especially sensitive to cancer treatment, leading to concerns among patients regarding their quality of life afterward. Side effects to the ovary include damage to the ovarian reserve, resulting in follicle loss, endocrine hormone deficiency, and infertility. It has been previously demonstrated that continuous treatment with 2 mg/kg cisplatin for 15 days can activate primordial follicles, suggesting that the response in the oocytes of primordial follicles was dependent on cisplatin concentration and administration frequency. However, our results demonstrate that continuous treatment with 2 mg/kg cisplatin for 15 days leads to the same consequence as with the continuous treatment of 5 mg/kg cisplatin: the death of oocytes in primordial follicles without indication of activation. Moreover, animals co-injected with melatonin and cisplatin did not display any significant differences from those treated with cisplatin only contrary to the known results. 6-hydroxymelatonin, a metabolite of melatonin, could not prevent follicle destruction, implying that melatonin does not confer the protection of ovarian follicles, either directly or indirectly. Altogether, our data support that fertoprotectants against cisplatin must target molecules that control cell death pathways in the oocytes of primordial follicles.

Progesterone-based timed AI protocols for Bos indicus cattle II: Reproductive outcomes of either EB or GnRH-type protocol, using or not GnRH at AI.

The aim of these experiments was to study ovarian dynamics and fertility of Bos indicus beef cattle submitted to 7-d progesterone (P4)-based fixed-time AI (FTAI) protocols using different hormonal treatments. In Exp. 1, 2 yr old Nelore heifers (n = 973) were randomly assigned to one of four treatments: EB-0 (estradiol benzoate, EB on D0 and no GnRH at AI), EB-G (EB on D0 and GnRH at AI), G-0 (GnRH on D0 and no GnRH at AI), or G-G (GnRH on D0 and at AI). On D0, heifers received an intravaginal P4 implant (0.5 g) for 7 d and EB (1.5 mg) or GnRH (16.8 µg). On D7, the P4 implant was withdrawn and heifers received cloprostenol (PGF; 0.5 mg) and estradiol cypionate (EC, 0.5 mg). Heifers in G groups also received PGF and eCG (200 IU) on D6, whereas EB heifers received eCG on D7. At FTAI on D9, only EB-G and G-G groups received GnRH (8.4 µg). In Exp. 2, Nelore cows (n = 804) received the same treatments (EB-0, EB-G, G-0, or G-G) using a 1.0 g P4 implant, 2.0 mg EB, and 300 IU eCG. Effects were considered significant when P ≤ 0.05. After treatment on D0, G had more ovulations than EB in heifers (60.3 [287/476] vs. 12.7% [63/497]) and cows (73.7 [83/112] vs. 24.4% [28/113]). Luteolysis after D0 was greater in EB than G in heifers (39.2 [159/406] vs. 20.0% [77/385]) and cows (25.5 [14/55] vs. 1.6% [1/64]). Heifers in G had larger follicles (mm) than EB on D7 (10.3 ± 0.2 vs. 9.2 ± 0.2) and at AI (11.9 ± 0.2 vs. 11.3 ± 0.2). Cows had larger follicles in G than EB on D7 (11.0 ± 0.3 vs. 9.9 ± 0.3) but not at AI. More estrus was observed in G than EB for heifers (80.3 [382/476] vs. 69.6% [346/497]) and cows (67.6 [270/400] vs. 56.2% [227/404]). There was no interaction between D0 and D9 treatments on pregnancy per AI (P/AI) in heifers (EB-0: 56.7 [139/245], EB-G: 53.6 [135/252], G-0: 52.6 [127/241], and G-G: 57.5% [135/235]). However, cows from EB-G had greater P/AI than EB-0 (69.5 [142/204] vs. 60.2% [120/200]), whereas P/AI for G-0 (62.7% [127/203]) was similar to G-G (60.9% [120/197]). In heifers, there was no interaction of GnRH at AI with estrus, however, cows that did not display estrus had greater P/AI if they received GnRH at AI (GnRH = 59.1 [91/154] vs. No GnRH = 48.2% [78/162]). Thus, protocols initiated with EB or GnRH for Bos indicus heifers and cows had differing ovarian dynamics but similar overall fertility, enabling their use in reproductive management programs. Treatment with GnRH at time of AI increased fertility in some instances in Bos indicus cows but not in heifers.

New infertility therapy effects of polysaccharides from Althaea officinalis leaf with emphasis on characterization, antioxidant and anti-pathogenic activity.

Characterization, antioxidant, anti-pathogenic and infertility therapy effects of polysaccharides from Althaea officinalis (marshmallow) leaf (AOLPS) were investigated. AOLPS was fractionated using ion-exchange chromatography, affording fractions of AOLPS-1, AOLPS-2, AOLPS-3 and AOLPS-4. The fractions were mainly composed of d-galactopyranose (α-(1 â†’ 4)-glycosidic bond) with the average molecular weight of 1220, 2240, 998 and 2670 Da, respectively which means it was a pectin-like polysaccharide. Differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FT-IR) techniques were employed to characterize the structure of purified polysaccharides. Compared with AOLPS-1, AOLPS-2 and AOLPS-4, AOLPS-3 had higher potential as a natural antioxidant and antimicrobial. At the same time, the infertility therapy effects of four fractions of AOLPS were in the order AOLPS-3 > AOLPS-4 > AOLPS-1 > AOLPS-2. The experimental study provides strong evidence to exploit A. officinalis leaf in food and pharma manufacturing processes and presents new benefit of this plant in infertility therapy.

The Use of a Biostimulant Composition to Increase Turkey Viability during the Key Critical Periods of Development.

The paper reports that the treatment of hatching turkey eggs with a mixture composed of colamine, succinic acid, serine, and pyridoxine hydrochloride increased the viability of embryos and reduced incubation wastes. This effect allowed increasing the hatching of turkey poults by 6.73% and the hatchability of eggs, by 4.43%. At the same time, a statistically significant decrease in the key lipid peroxidation products in one-day-old turkey poults was observed. In particular, the content of isolated double bonds decreased 1.47-fold (p < 0.01); diene conjugates, 1.67-fold (p < 0.01); triene conjugates, 1.46-fold (p < 0.05); oxidiene conjugates, 1.48-fold (p < 0.01); and Schiff bases, 1.3-fold compared to the control. All the above-mentioned positively affected survivability in the experimental group, which appeared to be increased by 1% compared to the control.

Effect of equine chorionic gonadotropin on reproductive performance in a dairy herd in Northern Queensland, Australia.

This study evaluated the effect of equine chorionic gonadotropin (eCG) on reproductive performance, when incorporated into the first Ovsynch + P4 synchronization following planned start mating (PSM) in pasture-based lactating dairy cows. Two synchrony programs were compared in a randomized controlled trial in Queensland, Australia. Lactating cows from a single dairy herd (n = 782) were randomly allocated to Control and eCG groups. Control cows had their estrous cycles synchronized by treatment with 100 µg gonadotropin releasing hormone (GnRH; im) and insertion of a progesterone (P4) releasing intravaginal device that contained 1.0 g of P4 on Day 0; removal of P4 device and administration of 500 µg of an analogue of PGF2α on Day 7 (cloprostenol; im); 100 µg im of GnRH on Day 9, and fixed-time artificial insemination (FTAI) on Day 10. The eCG group were treated the same as the Control group except for the addition of 400 IU of eCG, im on Day 7 of the first synchronized estrous cycle. Following the first insemination, non-pregnant cows from both groups had their estrous cycles synchronized with the same treatment protocol without using eCG. The effects of eCG on 42d cumulative incidence of pregnancy and pregnancy per AI (P/AI) were determined using logistic regression models. The effect of eCG on time to pregnancy was determined using Kaplan-Meier survival analysis and Cox proportional hazards models. Adjusted 42 d cumulative incidence of pregnancy for eCG and control groups were 47.2 and 39.3% respectively (Odds ratio [OR] = 1.38, 95% CI: 1.01-1.88). Hazard of pregnancy tended to be higher in eCG cows overall (Hazard ratio [HR] = 1.18, 95% CI: 0.99-1.41) and was significantly higher when restricting to the first 42 days after PSM (HR = 1.31, 95% CI: 1.04-1.64). Hazards of pregnancy were not different between groups when restricting to > Day 42 post PSM (HR = 1.00, 95% CI: 0.77-1.31). P/AI tended to be higher in eCG treated cows at the first AI (44.0 vs 37.7%, OR = 1.30, 95% CI: 0.94-1.78). P/AI for second and third AIs were not significantly different between groups. In this herd, a single treatment of eCG at the first synchronized estrus after PSM improved reproductive performance in the short term, but not at subsequent inseminations.

Fertility enhancing efficacy of Cicer arietinum in male albino mice.

The present study was conducted to investigate the effect of incorporating Cicer arietinum in the diet on the testicular functions of the male mice. Seventy-two mice were divided equally into four groups that were daily fed a diet containing 0, 20, 30 and 50% of C. arietinum seeds, respectively. After 7, 14 and 21 days of starting the experiments, the mice were anesthetized and euthanized to collect the blood, testes, epididymis and seminal vesicles. The present results showed that the increased percentage of C. arietinum in the diet caused significant elevations in the serum levels of testosterone and luteinizing hormone (LH), sperm concentration, sperm motility as well as the testicular levels of antioxidants including glutathione (GSH), glutathione peroxidase (GPx) and catalase (CAT), in comparison to the controls. On the other hand, marked reductions in the sperm abnormality, testicular levels of malondialdehyde (MDA), the percentage of DNA damage in tail and tail moment (TM) were observed in the mice that received a diet containing C. arietinum as compared to the controls. Both the sperms and testes of the mice fed a diet containing C. arietinum in the diet showed a normal intact appearance of the electrophoresed genomic DNA on agarose, as those of the controls. In conclusion, C. arietinum is not only a safe ingredient in the fast-food but also an enhancer of the testicular functions.

Walnut leaf extract acts as a fertility agent in male Wistar albino rats - A search for herbal male fertility enhancer.

Background Walnut leaf is one of the many medicinal plants used in folklore as male fertility enhancers. The present work was therefore undertaken with an aim to scientifically validate this claim. As such, we evaluated the effect of the aqueous extract from walnut leaves on biomolecules related to fertility in adult male rats and its mode of action as fertility-enhancing agent. Methods Twenty-five rats were randomly divided into five groups of five animals each; Group 1 served as control and received normal (0.9%) saline only; Groups II, III, IV received 50, 500, 1,000 mg/kg body weight (BW) of T. conophorum leaf extract orally, while Group V served as standard and was given suspension of clomiphene citrate orally at the dose of 1.04 mg/kg/ml BW. The extract and drug were given daily and the experiment lasted for 21 consecutive days. Results The testicular biochemical parameters in treated groups showed significant (p<0.05) increase in lactate dehydrogenase activity activity, Glucose-6-phosphate dehydrogenase (G-6PDH) activity, glycogen content, 3ß and 17ß hydroxysteroid dehydrogenase activities and testicular and epididymal Zn and Se contents with a significant decrease in cholesterol content. A significant increase in testis weight and epididymis weight were also observed. Also, a significant (p<0.05) increase in the level of serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone, sperm count, motility, viability and a decrease in sperm abnormality were observed in the various treated groups when compared with the control group. This increment was concentration dependent, while the extract at the highest concentration showed a more pronounced effect than the standard drug. Also, no sperm DNA fragmentation index was found in all the treatment groups. Photomicrographs from light and scanning electron microscopy showed large fenestrae of interstitial tissue, large fluid space and intact seminiferous epithelium layers fully packed with spermatogenic cells in treated groups than the control group. Conclusions The present study has demonstrated that Tetracarpidium conophorum leaf possesses fertility-enhancing property and have useful effects on spermatogenesis and sperm parameters in rats.

Effects of melatonin implantation on the fertility potentials of Kivircik and Charollais ewes and rams during the non-breeding season.

This study examined the effect of melatonin implantation during the non-breeding season on the reproductive performance of ewes and the testicular dimensions of rams. In seasonally anestrus Kivircik and Charollais ewes and rams were subjected to melatonin. Estrus response was significantly higher in treated than control ewes of both breeds (p<0.001). The pregnancy rate was significantly lower (p<0.001) in the control than in the treated animals. The twinning rate was significantly lower in melatonin implanted Kivircik than Charollais ewes (p<0.05). The testicular dimensions after 42 days of melatonin treatment increased in both breeds. Scrotal length (SL) increased in Kivircik and Charollais rams (p<0.01). The increase in scrotal circumference (SC) was more marked in the Charollais (P<0.01) than in the Kivircik rams. There was a large increase in testicular volume (TV) in both Kivircik (p<0.01) and Charollais (p<0.001) rams. This study shows that melatonin implants can be applied to induce estrus in ewes approximately four months earlier than breeding season. Melatonin implantation in the non-breeding season significantly increased testicular dimensions in Kivircik and Charollais rams thus increasing their reproductive potential.

Two-cell embryos are more sensitive than blastocysts to AMPK-dependent suppression of anabolism and stemness by commonly used fertility drugs, a diet supplement, and stress.

PURPOSE: This study tests whether metformin or diet supplement BR-DIM-induced AMP-activated protein kinase (AMPK) mediated effects on development are more pronounced in blastocysts or 2-cell mouse embryos. METHODS: Culture mouse zygotes to two-cell embryos and test effects after 0.5-1 h AMPK agonists' (e.g., Met, BR-DIM) exposure on AMPK-dependent ACCser79P phosphorylation and/or Oct4 by immunofluorescence. Culture morulae to blastocysts and test for increased ACCser79P, decreased Oct4 and for AMPK dependence by coculture with AMPK inhibitor compound C (CC). Test whether Met or BR-DIM decrease growth rates of morulae cultured to blastocyst by counting cells. RESULT(S): Aspirin, metformin, and hyperosmotic sorbitol increased pACC ser79P ~ 20-fold, and BR-DIM caused a ~ 30-fold increase over two-cell embryos cultured for 1 h in KSOMaa but only 3- to 6-fold increase in blastocysts. We previously showed that these stimuli decreased Oct4 40-85% in two-cell embryos that was ~ 60-90% reversible by coculture with AMPK inhibitor CC. However, Oct4 decreased only 30-50% in blastocysts, although reversibility of loss by CC was similar at both embryo stages. Met and BR-DIM previously caused a near-complete cell proliferation arrest in two-cell embryos and here Met caused lower CC-reversible growth decrease and AMPK-independent BR-DIM-induced blastocyst growth decrease. CONCLUSION: Inducing drug or diet supplements decreased anabolism, growth, and stemness have a greater impact on AMPK-dependent processes in two-cell embryos compared to blastocysts.

Phytochemical and biological assessments on Lipidium meyenii (maca) and Epimidium sagittatum (horny goat weed).

The effects of Lipidium meyenii (maca, LM) and Epimidium sagittatum (horny goat weed, ES) have been investigated due to their involvement in fertilization. Both of the drugs showed good results before, during and after fertilization in male and female mice. The results revealed that the crude extract of Lipidium meyenii caused a significant decrease in the no. of writhes at 300 and 500mg/kg (p<0.05) as compare to control, Epimidium sagittatum and standard drug. The gross behavioral, open field, exploratory behaviour, forced swimming test for stress, diuretic activity, chronic toxicity with the effect on reproduction of both male and female and change in body weight were also studied. The phytochemical study showed the presence of tannin, alkaloid, carbohydrate, rich protein and absence of sterol in LM, whereas ES shows presence of sterol and less protein. LS improve in muscle activity and exploratory behaviours without any toxic effects on mice and their pups. It does not have diuretic effect for first two hour but act normally after initial phase of drug therapy. Epimidium sagittatum has dual action that is at low dose it has slight stimulation action and at high dose little depressive effect. ES also has some diuretic effect. Overall these results suggest that LM is highly effective remedy for treatment of impotency and reduces stress and depression, because of dual effect ES not only suggested as an anxiolytic medicine but also effective in female hormonal disorder.

Antiinflamatorios no esteroideos e infertilidad / Non-steroidal anti-inflammatory drugs and infertility

No disponible

Spermaurin, an La1-like peptide from the venom of the scorpion Scorpio maurus palmatus, improves sperm motility and fertilization in different mammalian species.

STUDY QUESTION: Is it possible to identify original compounds that are able to enhance sperm motility from the venom of the scorpion Scorpio maurus palmatus? SUMMARY ANSWER: We identified a potent disulfide-rich peptide (DRP) of 73 amino acids that significantly improved the motility of fresh and frozen-thawed sperm in different mammalian species, including human, and improved fertilization outcome in mouse IVF experiments. WHAT IS KNOWN ALREADY: Any disturbance of sperm motility has a strong impact on fertilization and can lead to subfertility or infertility. Significant efforts have, therefore,  been made to identify pharmacological drugs that might improve sperm motility. Such compounds are particularly useful in azoospermia to improve testicular sperm extraction and in the domain of cryopreservation because the motility of frozen-thawed sperm is reduced. STUDY DESIGN, SIZE, DURATION: This was a basic science/medical research study aimed at identifying original compounds from a library of venoms able to enhance mammalian sperm motility, including human. We first identified in the venom of a scorpion S. m. palmatus a fraction able to potently activate sperm motility. We next purified and characterized the compound by liquid chromatography, mass spectrometry and peptide synthesis. Finally, the potency and toxicity of both purified and synthetic versions of the identified compound on sperm motility were assessed using different in vitro tests in different mammalian species. PARTICIPANTS/MATERIALS, SETTING, METHODS: For human sperm, biological samples were collected from normozoospermic donors and subfertile patients attending a reproduction department for diagnostic semen analysis. Testicular sperm was collected from cynomolgus monkeys (Macaca fascicularis) euthanized for the needs of specific authorized research projects. The peptide was also tested on bovine and mouse epidydimal sperm. We measured different sperm motility parameters with a computer-assisted sperm analysis system in the presence or absence of the peptide. MAIN RESULTS AND THE ROLE OF CHANCE: Size exclusion chromatography enabled us to isolate a fraction of the venom of S. m. palmatus able to increase sperm motility. By liquid chromatography and mass spectrometry, a peptide comprising 73 amino acids with 4 disulfide bridges was identified as responsible for the biological activity and called 'spermaurin'. The identity of spermaurin was confirmed by chemical synthesis. We showed that the peptide increased the motility of fresh and frozen-thawed human sperm. We observed that the potency of the peptide was higher on fresh ejaculated spermatozoa with a low motility, achieving a 100% increase of curvilinear velocity in poorly performing sperm. We also demonstrated that peptide is effective on bovine and mouse fresh epididymal, bovine frozen-thawed ejaculated and fresh non-human primate testicular sperm. Finally, in mouse IVF, the production of 2-cell embryos was increased by 24% when sperm were treated with the peptide. LIMITATIONS, REASONS FOR CAUTION: This work is an in vitro evaluation of the ability of spermaurin to improve sperm motility parameters. Another limitation of this study is the small number of human sperm samples tested with the natural (n = 36) and synthetic (n = 12) peptides. Moreover, the effect of the peptide on IVF outcome was only tested in mouse and further tests with human and bovine gametes are required to confirm and extend this result in other mammalian species. WIDER IMPLICATIONS OF THE FINDINGS: This work confirms our initial study showing that venoms represent an interesting source of molecules that are able to modify sperm physiology. Moreover, this work presents the first demonstrated biological action of a venom peptide from the scorpion S. m. palmatus with sequence similarities to La1 peptide from Liocheles australasiae (Wood scorpion), a widespread family of DRPs. LARGE SCALE DATA: Not applicable. STUDY FUNDING/COMPETING INTEREST(S): This work is part of the project 'LAB COM-14 LAB7 0004 01-LIPAV', funded by the program LabCom 2014 from the French Research Agency (ANR). Dr Arnoult reports grants from IMV Technologies during the conduct of the study. In addition, Drs Arnoult, Martinez, Ray and Schmitt have a patent EP16305642.7 pending containing some of the information presented in this manuscript.