Reproductive Organ Weights Research Articles

The Effect of Ketoconazole and Quinestrol Combination on Reproductive Physiology in Male Mice

This study investigates whether ketoconazole, a CYP3A4 inhibitor, can enhance the suppressive effects of quinestrol on reproductive capacity, potentially allowing for a reduced quinestrol dosage while maintaining its efficacy. A total of 104 healthy adult male mice were divided into two groups, assessed at 10 and 30 days. Within each group, six treatment categories were tested: the control (CK), quinestrol alone (Q1, Q5), and quinestrol combined with varying doses of ketoconazole (Q1 + K0.4, Q1 + K2, Q5 + K0.4). The key parameters measured included internal and reproductive organ weights, sperm density, sperm motility, sperm abnormalities, and CYP3A4 enzyme content in intestinal and liver tissues. After 10 days, the combination of a low dose of quinestrol with ketoconazole (Q1 + K0.4) showed the most significant pronounced effects in reducing reproductive potential, with notable reductions in epididymal weight, sperm density, sperm abnormality rate and vitality, serum hormone levels, and CYP3A4 content in the small intestine and liver. Although some reproductive parameters returned to near-baseline levels after 30 days, the Q1 + K0.4 regimen continued to exhibit reduced seminal vesicle weight and testosterone levels. Importantly, the combination did not significantly increase CYP3A4 enzyme content, indicating effective metabolic inhibition. The combination of quinestrol and ketoconazole, especially the Q1 + K0.4 regimen, demonstrated the most noticeable impact on reducing reproductive capacity. This regimen significantly reduced key reproductive parameters and showed strong metabolic inhibition, suggesting that ketoconazole substantially enhances the efficacy of quinestrol in fertility control.

Responses in organs, sperm, steroid hormones and CYP450 enzyme in male mice treated by quinestrol only or in conjunction with clarithromycin

Pest rodents persistently undermine crop yields and food security. Fertility control could be a viable alternative for managing rodent populations. This study investigates the antifertility effects of various concentrations of clarithromycin combined with 1.0 mg/kg quinestrol on male rodents to determine an effective contraceptive dose that minimizes quinestrol usage, addressing key concerns such as potential environmental residue, which may impact ecological balance, and poor palatability, which could reduce ingestion and limit the sterilant’s effectiveness. Male mice were divided into five groups and administered different doses of clarithromycin or clarithromycin and quinestrol for three consecutive days, while the control group received sunflower seed oil only. After seven days, organ weights, reproductive organ weights, sperm density, serum hormone levels, and CYP3A4 content in small intestinal and liver tissues were measured to assess persistent effects. Compared with the control group, all treatment groups had significant reductions in epididymal weight, seminal vesicle weight, and serum T and LH levels. Higher concentrations of clarithromycin (2 mg/kg and 10 mg/kg) significantly impacted reproductive metrics, including sperm density, organ weights, and serum LH and testosterone levels, though complete sterilization was not achieved, with more than 60 million cauda epididymal spermatozoa remaining. However, the combination demonstrated potential as an effective strategy for male fertility control. The combination of 2.0 mg/kg clarithromycin and quinestrol can mitigate organ enlargement seen with quinestrol alone. This combination also decreased total enzyme content, thereby diminishing quinestrol’s induction of CYP3A4, which may increase the sterilization effectiveness of the treatment.

Neonatal undernutrition induced by litter size expansion alters testicular parameters in adult Wistar rats.

Several models of maternal undernutrition reveal impairment of testicular development and compromise spermatogenesis in male offspring. The expansion of the litter size model, valuable for studying the impact of undernutrition on early development, has not yet been used to evaluate the consequences of early undernutrition in the adult male reproductive system. For this purpose, pups were raised in either normal litter (ten pups/dam) or large litter (LL; sixteen pups/dam). On postnatal day 90, sexual behaviour was evaluated or blood, adipose and reproductive tissues were collected for biochemical, histological and morphological analysis. Adult LL animals were lighter and thinner than controls. They showed increased food intake, but decrease of retroperitoneal white adipose tissue weight, glycaemia after oral glucose overload and plasma concentration of cholesterol. Reproductive organ weights were not altered by undernutrition, but histopathological analysis revealed an increased number of abnormal seminiferous tubules and number of immature spermatids in the tubular lumen of LL animals. These animals also showed reduction in total spermatic reserve and daily sperm production in the testes. Undernutrition decreased the number of Sertoli cells, and testosterone production was increased in the LL group. Mitochondrial activity of spermatozoa remained unchanged between experimental groups, suggesting no significant impact on the energy-related processes associated with sperm function. All animals from both experimental groups were considered sexually competent, with no significant difference in the parameters of sexual behaviour. We conclude that neonatal undernutrition induces histological and physiological testicular changes, without altering sperm quality and sexual behaviour of animals.

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.

7788 Importance of Neuronal STAT3, but Not ERK2 or mTOR, for Pubertal Timing and Reproductive Activity in Mice

Abstract Disclosure: R.A. Lord: None. M.A. Inglis: None. G.M. Anderson: None. The adipose-derived hormone leptin is important for regulating reproduction. The canonical JAK2/STAT3 pathway is the best-characterised leptin receptor signalling pathway. Neural STAT3 deletion is known to cause obesity; however, its reproductive influence is less understood. This experiment investigated whether STAT3 knockout from brain neurons or AgRP neurons, a neuronal population necessary for normal pubertal timing and reproduction, would unveil the necessity of STAT3 in reproductive function. We also tested the role of ERK2 and mTOR, two alternative leptin signalling molecules.Transgenic mice with a neuronal knockout were created via the Cre-loxP system. CamKinaseIIα-Cre mice were crossed with STAT3, mTOR or ERK2 floxed mice. AgRP-Cre mice were crossed with STAT3 floxed mice for STAT3 knockout in AgRP neurons. All groups were compared to Cre-negative littermate controls (n=6-12/group). Puberty onset was assessed post-weaning by examining genitalia development. Reproductive cyclicity and organ weights were measured in adults. Metabolic effects were evaluated through body weight, abdominal fat and fasting glucose measurements. Brain tissue analysis evaluated cellular responses to leptin for STAT3, ERK2, and mTOR. Data presented as mean ± SEM.Mice with ERK2 KO or mTOR KO showed no reproductive or metabolic deficits compared to controls. In marked contrast, neuronal STAT3 KO mice showed significantly increased body weight by 5 weeks of age and a 6-fold increase in abdominal adiposity as adults (both p<0.001 using two-way ANOVA and Student’s t-test respectively) compared to controls. Males had a significant 5-day delay in age at preputial separation (KO: 32.1±2.09 d; Control: 26.8±0.45 d, p<0.01, Student’s t-test) while females had a significant 7-day delay in vaginal opening (KO: 33.0±1.85 d, Control: 26.6±0.37 d, p<0.05, Student’s t-test), a 9-day delay in first estrus (KO: 37.8±1.89 d; Control: 29.4±0.65 d, p<0.01, Student’s t-test) and pronounced acyclicity. Neuronal STAT3 KO mice also had a >2-fold elevation in fasting glucose levels (p<0.001, Student’s t-test) and regressed reproductive organs. Female mice with STAT3 knockout in AgRP neurons showed significantly increased body weight (by 3 weeks [p<0.001], two-way ANOVA) and a significant 3-day delay in first estrus (KO: 31.1±0.71 d, Control: 28.6±0.45 d, p<0.01, Student’s t-test). These data show that neuronal STAT3 is critical for correctly timed puberty and subsequent fertility in male and female mice, whereas mTOR and ERK2 are not essential. These results have prompted a re-evaluation of previous conclusions about the role of STAT3 from experiments using LepR-Cre mice. Additionally, AgRP neuronal requirements for STAT3 exactly recapitulate AgRP requirements for leptin receptors. A better grasp of leptin signalling pathways will improve our understanding of how infertility arises due to metabolic disease. Presentation: 6/3/2024

Assessment of the efficacy of a gonadotropin releasing factor (GnRF) analog to suppress ovarian function in gilts under pre-clinical and clinical conditions.

The administration of a gonadotropin releasing factor (GnRF) analog to pigs has proven to induce antibodies against endogenous GnRF. In gilts (young female pigs), the subsequent blocking of GnRF activity by specific antibodies results in a temporary suppression of ovarian activity and sexual maturation. One pre-clinical and two clinical studies were conducted to assess the ability of the GnRF analog to produce immunologically suppression of the ovarian function, preventing gilts from reaching puberty before harvest, at 27 weeks of age. In the three studies, a significant reduction of size and weight of reproductive organs and gilts in oestrus was demonstrated in vaccinated gilts compared with intact gilts. A significant increase in anti-GnRF antibody levels in sera was observed after the 2nd dose, which lasted until the end of the study in each of the protocols used. Progesterone levels were significantly reduced from 6 to 8 weeks after 2nd vaccination in clinical studies 2 and 1 respectively, and from 6 weeks after 2nd vaccination in the pre-clinical study. Estradiol levels were below the limit of detection for clinical study 2 and significantly reduced in vaccinated gilts at the end of the pre-clinical study and the clinical study 1. Vaccination of gilts with a GnRF analog with two different protocols (1st dose from 10 to 14 weeks of age, and a 2nd dose 8 or 4 weeks later) was effective in reducing the development of puberty for at least 9 weeks post 2nd dose. These results confirm the flexibility of vaccination programs for veterinarians and producers which can be adapted to pig management practices in commercial farms.

Effects of the aqueous extract of Hibiscus sabdariffa on male fertility and reproductive performance in the rat model

Hibiscus sabdariffa is a popular herb and has long been widely utilised for ethnomedicinal purposes. Despite its benefits, there is very scarce information available on the reproductive toxicity of this plant. The present study aimed to investigate the potential effects of the aqueous extract of H. sabdariffa (AEHS) on the male reproductive system of Sprague Dawley rats. A total of forty males were administered with AEHS at the different dosages of 250, 500, 1000 mg/kg/day or distilled water (control), by oral gavage daily throughout the 60-day treatment periods, which comprised three phases: pre-mating, mating, and post-mating. Results obtained demonstrated that the effects of AEHS on the reproductive system of male rats were slightly significant for certain doses. No mortality and any signs of physical and behavioural toxicity were observed. The mating performance was also not affected. Similarly, the mean body weight of rats was statistically not affected. However, the reproductive organ weights were found to be considerably different. Furthermore, AEHS increased the testosterone levels and sperm counts of the 250 and 1000 mg/kg dose groups, while the 500 mg/kg dose group showed considerably low levels for both parameters. The 500 mg/kg dose group was detected to exhibit inconsistent data for several parameters when compared to other groups, which might be caused by confounding factors instead of AEHS. Therefore, the current data suggest that AEHS should be consumed with caution particularly when the daily dose exceeds 250 mg/kg of body weight.

Anti-implantation and uterotonic properties of Mentha pulegium L. in female Sprague-Dawley rats

Background: Some traditional herbs disrupt endocrine-endometrial synchrony, affecting embryo-endometrium communication during fertility. Hormonal imbalances cause non-receptive conditions, leading to anti-implantation or abortion. Historically, Mentha pulegium has served for contraceptive and abortive purposes. Its effects on the post-coital contraceptive and hormonal activities were evaluated. Methods: Thirty-six Sprague-Dawley female rats were selected based on the presence of copulation plugs and received 200, 500, and 1000 mg/kg of Hydroethanolic leaf extract of Mentha pulegium L. (MPE) for seven days. Reproductive organ weights and serum estrogen and progesterone levels were measured. The resorption index, anti-implantation activity, and pre-implantation loss were also calculated using the number of implantation sites and resorptions in all treatments. Data were presented as mean±standard error mean (SEM), and significance was defined as p<0.05 using one-way ANOVA. Results: Post-coital administration of MPE resulted in resorptive, pre-implantation loss, and anti-implantation activity. A dose of 200 mg/kg reduced the number of implantations and exhibited a high resorption index, percentage pre-implantation loss, and anti-implantation activity. A marked decline in serum progesterone levels and a significant reduction in serum estrogen and progesterone ratio was observed at 200 mg/kg MPE. A significant increase in uterine weight was observed in the 500 mg/kg treatment. Doses of 500 and 1000 mg/kg resulted in a significant reduction in anti-implantation activity. Conclusions: The observed anti-implantation activity and pre-implantation loss suggest the abortifacient properties of MPE. However, its effects were seen to be dose-dependent.

Asprosin-induced alterations in female rat puberty and reproductive hormonal profiles

Objective To investigate the comprehensive effects of daily chronic asprosin administration on various pubertal and reproductive parameters in female rats. This study aims to elucidate the role of asprosin in regulating the onset of puberty and its influence on hormonal profiles and ovarian histology. Methods Asprosin was administered intraperitoneally (i.p.) at a dose of 500 ng/kg daily for eight weeks. Hormonal assays and histological analyses were performed to evaluate the effects of asprosin on the onset of puberty and reproductive function. Results Daily chronic administration of asprosin accelerated the onset of the first oestrus. Hormonal assays revealed significant elevations in serum levels of Follicle-Stimulating Hormone (FSH) and Oestradiol (E2), while Inhibin B levels decreased. Histological evaluations demonstrated an increased number of primary and secondary follicles in ovarian tissue, without affecting primordial follicle counts or reproductive organ weights. Conclusions Role of adipokines in regulating puberty and reproductive function has increasingly gained recognition. This study aimed to provide the first comprehensive examination of the effects of daily chronic asprosin administration on pubertal and reproductive parameters in female rats. Utilising hormonal assays and histological analyses, asprosin was administered intraperitoneally (i.p.) at a dose of 500 ng/kg, daily, for eight weeks. Our findings revealed that daily chronic administration of asprosin accelerated the onset of the first oestrus. Hormonal assays showed significant elevations in serum levels of Follicle-Stimulating Hormone (FSH) and Oestradiol (E2), while Inhibin B levels decreased. Histological evaluations demonstrated an increased number of primary and secondary follicles in ovarian tissue, without affecting primordial follicle counts or reproductive organ weights. These results provide new insights into asprosin’s role in advancing the age of first oestrus and modulating hormonal profiles, thereby offering potential benefits to the female reproductive system.

Preclinical Appraisal of the Aphrodisiac Effects of Emblica officinalis Seed Extract on Stress-induced Sexual Behavior in Albino Rats

Background: The king of herbs, Emblica officinalis, is one of the most important herbs in Ayurveda. It contains significant amounts of Vitamin C and has been reported to have antioxidant, anticancer, antiretroviral, antidepressant, antiulcerogenic, wound healing, and many other medicinal properties. Objective: The current study is designed to investigate the aphrodisiac effects of E. officinalis seed extract on albino Wistar rats as well as its effects on stress-related sexual behaviour. Materials and Methods: The aphrodisiac effect of E. officinalis was evaluated by mating the pretreated male rats with female rats. For 30 days, test group rats (n=6) were given methanolic extracts (95%) from E. officinalis seeds (500 and 1000 mg/kg). Control rats received saline. Standard group rats received testosterone (0.5 mg/ kg, i.m). The sexual behavior study tracked Mount Latency (ML), Intromission Latency (IL), Mounting Frequency (MF), Intromission Frequency (IF), sniffing, and licking on days 0 through 30. After 30 days, rats were sacrificed, and the anabolic effect was assessed using body weight, reproductive organ weight, sperm concentration, and histopathology of the testes. The stress was induced by immobilization stress in the stress-affected alteration in the sexual behavior model, and the above procedure was repeated for evaluation. Results: The 95% methanolic extract (1000 mg/kg) of E. officinalis significantly reduced ML and IL while significantly increasing MF, IF, sniffing, licking, body weight, reproductive organ weight, and sperm concentration. Methanolic extract of E. officinalis increased sexual activities in the stress-free group and restored the stress-affected group's altered sexual behaviour. Conclusion: The current study's findings indicate that 95% methanolic extract of E. officinalis has dose-dependent aphrodisiac activity and restores sexual behavior in a stress-induced group.

Effect of tannic acid on adiponectin and gonads in male Brandt’s voles (Lasiopodomys brandtii)

Adiponectin regulates steroid production and influences gonadal development. This study examined the effects of tannic acid (TA) on the adiponectin levels and gonads of male Brandt’s voles. Male Brandt’s voles aged 90 d were randomly separated into three groups: a control group (provided distilled water), a group given 600 mg∙kg-1 TA, and a group that received 1200 mg∙kg-1 TA (continuous gavage for 18 d). In this study, we examined the effects of TA on the adiponectin, antioxidant, and inflammatory levels in the testes. Furthermore, we examined the expression of important regulatory elements that influence adiponectin expression and glucose utilisation. In addition, the body weight, reproductive organ weight, and testicular shape were assessed. Our study observed that TA treatment increased serum adiponectin levels, DsbA-L and Ero1-Lα transcription levels, and AdipoR1, AMPK, GLUT1, and MCT4 expression levels in testicular tissue. TA enhanced pyruvate and lactic acid levels in the testicular tissue, boosted catalase activity, and reduced MDA concentrations. TA reduced the release of inflammatory factors in the testicular tissues of male Brandt’s voles. TA increased the inner diameter of the seminiferous tubules. In conclusion, TA appears to stimulate adiponectin secretion and gonadal growth in male Brandt’s voles while acting as an antioxidant and anti-inflammatory agent.

Episodic ozone exposure in Long-Evans rats has limited effects on cauda sperm motility and non-coding RNA populations

Epidemiological evidence suggests the potential for air pollutants to induce male reproductive toxicity. In experimental studies, exposure to ozone during sensitive windows in the sperm lifecycle has been associated with impaired sperm motility. Subsequently, we sought to investigate the effects of episodic exposure to ozone during sperm maturation in the rat. Long-Evans rats were exposed to either filtered air or ozone (0.4 or 0.8 ppm) for five non-consecutive days over two weeks. Ozone exposure did not impact male reproductive organ weights or sperm motility ∼24 hours following the final exposure. Furthermore, circulating sex hormones remained unchanged despite increased T3 and T4 in the 0.8 ppm group. While there was indication of altered adrenergic signaling attributable to ozone exposure in the testis, there were minimal impacts on small non-coding RNAs detected in cauda sperm. Only two piwi-interacting RNAs (piRNAs) were altered in the mature sperm of ozone-exposed rats (piR-rno-346434 and piR-rno-227431). Data across all rats were next analyzed to identify any non-coding RNAs that may be correlated with reduced sperm motility. A total of 7 microRNAs (miRNAs), 8 RNA fragments, and 1682 piRNAs correlated well with sperm motility. Utilizing our exposure paradigm herein, we were unable to substantiate the relationship between ozone exposure during maturation with sperm motility. However, these approaches served to identify a suite of non-coding RNAs that were associated with sperm motility in rats. With additional investigation, these RNAs may prove to have functional roles in the acquisition of motility or be unique biomarkers for male reproductive toxicity.

Microplastic presence in dog and human testis and its potential association with sperm count and weights of testis and epididymis.

The ubiquitous existence of microplastics and nanoplastics raises concerns about their potential impact on the human reproductive system. Limited data exists on microplastics within the human reproductive system and their potential consequences on sperm quality. Our objectives were to quantify and characterize the prevalence and composition of microplastics within both canine and human testes and investigate potential associations with the sperm count, and weights of testis and epididymis. Using advanced sensitive pyrolysis-gas chromatography/mass spectrometry, we quantified 12 types of microplastics within 47 canine and 23 human testes. Data on reproductive organ weights, and sperm count in dogs were collected. Statistical analyses, including descriptive analysis, correlational analysis, and multivariate linear regression analyses were applied to investigate the association of microplastics with reproductive functions. Our study revealed the presence of microplastics in all canine and human testes, with significant inter-individual variability. Mean total microplastic levels were 122.63 µg/g in dogs and 328.44 µg/g in humans. Both humans and canines exhibit relatively similar proportions of the major polymer types, with PE being dominant. Furthermore, a negative correlation between specific polymers such as PVC and PET and the normalized weight of the testis was observed. These findings highlight the pervasive presence of microplastics in the male reproductive system in both canine and human testes, with potential consequences on male fertility.

Genetic parameters for cloacal gland, sexual maturity, reproductive organs weight, and body weight in meat-type quail

Selection to increase body weight in poultry can hamper reproduction traits and compromise production efficiency. Thus, attention to reproduction traits is essential to improving the sustainability of breeding programs. Data from a domestic quail breeding program for meat production were used to estimate genetic parameters. We analyzed five traits: 4-week body weight, age at sexual maturity for males and females, cloacal gland area, female, and male reproductive organs weights. A multi-trait mixed model analysis with fixed effects of generation/hatch was performed, assuming environmental covariance equals zero for sex-limited traits. Heritability estimates range from low to moderate for male sexual maturity and cloacal gland area, and high for other traits. Intersexual genetic correlation for age at sexual maturity is positive, which can lead to correlated responses in the other sex. Reproductive organs weights are genetically correlated with body weight, but not significantly between sexes and nor with sexual maturity. Genetic correlations for the cloacal gland area were positive with body weight and negative with age at sexual maturity of males and females, demonstrating a potential use of this trait for selection with favorable outcomes in reproduction. The use of the cloacal gland area can be used in the same way as the scrotal circumference in mammals, improving female reproduction traits by selecting a trait recorded in males.

Effect of Curcuma longa extract on reproduction function in mice and testosterone production in Leydig cells.

Curcuma longa, best known for its culinary application as the main constituent of curry powder, has shown potential impact on the reproductive system. This study aimed to investigate the efficacy of Curcuma longa extract (CLE) on Kidney-Yang deficiency mice induced by hydrocortisone and the possible roles in testosterone secretion in Leydig cells. We evaluated male sexual behaviour, reproductive organ weight, testosterone levels, and histological tissue changes in hydrocortisone-induced mice. CLE effectively reversed hydrocortisone-induced Kidney-Yang deficiency syndrome by improving sexual behaviour, testis and epididymis weight, testosterone levels and reducing pathological damage. Our invitro study further indicated that CLE stimulated testosterone production via upregulating the mRNA and protein expression of steroidogenic enzymes in Leydig cells. It significantly improved H89-inhibited protein expression of StAR and cAMP-response element-binding (CREB), as well as melatonin-suppressed StAR protein expression. The data obtained from this study suggest that CLE could alleviate Kidney-Yang deficiency symptoms and stimulate testosterone production by upregulating the steroidogenic pathway. This research identifies CLE as a potential nutraceutical option for addressing testosterone deficiency diseases.

Sperm DNA methylation defects in a new mouse model of the 5,10-methylenetetrahydrofolate reductase 677C>T variant and correction with moderate dose folic acid supplementation.

5,10-Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that plays a key role in providing methyl groups for DNA methylation, including during spermatogenesis. A common genetic variant in humans (MTHFR 677C>T) results in reduced enzyme activity and has been linked to various disorders, including male infertility. A new animal model has been created by reproducing the human equivalent of the polymorphism in mice using CRISPR/Cas9. Biochemical parameters in the Mthfr 677TT mice recapitulate alterations found in MTHFR 677TT men. Our aims were to characterize the sperm DNA methylome of the Mthfr 677CC and TT mice on a control diet (2 mg folic acid/kg diet) and assess the effects of folic acid supplementation (10 mg/kg diet) on the sperm DNA methylome. Body and reproductive organ weights, testicular sperm counts, and histology were examined. DNA methylation in sperm was assessed using bisulfite pyrosequencing and whole-genome bisulfite sequencing (WGBS). Reproductive parameters and locus-specific imprinted gene methylation were unaffected by genotype or diet. Using WGBS, sperm from 677TT mice had 360 differentially methylated tiles as compared to 677CC mice, predominantly hypomethylation (60% of tiles). Folic acid supplementation mostly caused hypermethylation in sperm of males of both genotypes and was found to partially correct the DNA methylation alterations in sperm associated with the TT genotype. The new mouse model will be useful in understanding the role of MTHFR deficiency in male fertility and in designing folate supplementation regimens for the clinic.

Infertility Improvement after Medical Weight Loss in Women and Men: A Review of the Literature.

Infertility is a modern health problem. Obesity is another expanding health issue associated with chronic diseases among which infertility is also included. This review will focus on the effects of weight loss by medical therapy on fertility regarding reproductive hormonal profile, ovulation rates, time to pregnancy, implantation rates, pregnancy rates, normal embryo development, and live birth rates. We comprised medicine already used for weight loss, such as orlistat and metformin, and emerging medical treatments, such as Glucagon-Like Peptide-1 receptor agonists (GLP-1 RA). Their use is not recommended during a planned pregnancy, and they should be discontinued in such cases. The main outcomes of this literature review are the following: modest weight loss after medication and the duration of the treatment are important factors for fertility improvement. The fecundity outcomes upon which medical-induced weight loss provides significant results are the female reproductive hormonal profile, menstrual cyclicity, ovulation and conception rates, and pregnancy rates. Regarding the male reproductive system, the fertility outcomes that feature significant alterations after medically induced weight loss are as follows: the male reproductive hormonal profile, sperm motility, movement and morphology, weight of reproductive organs, and sexual function. The newer promising GLP-1 RAs show expectations regarding fertility improvement, as they have evidenced encouraging effects on improving ovulation rates and regulating the menstrual cycle. However, more human studies are needed to confirm this. Future research should aim to provide answers about whether medical weight loss therapies affect fertility indirectly through weight loss or by a possible direct action on the reproductive system.

Efecto del extracto de Boswellia serrata sobre el daño testicular inducido por Metotrexato

This study aimed to determine the effect of Boswellia serrata extract on Methotrexate– induced testicular damage by evaluating antioxidant system, reproductive organ weights, some spermatological parametres and serum Testesterone levels. For this purpose, 40 Sprague Dawley rats were divided into 4 groups. 1. Control Group (n=10): No treatment was given for 10 days. 2. B. serrata Group (n=10): B. serrata was given by gavage at a dose of 500 mg·kg-1 for 10 days. 3. Methotrexate Group (n=10): Methotrexate was given intraperitoneally as a single dose of 20 mg·kg-1. 4. Methotrexate + B. serrata Group (n=10): After methotrexate was given intraperitoneally as a single dose of 20 mg·kg-1, 500 mg·kg-1 B. serrata was given by gavage for 10 days. It was determined that B. serrata significantly increased serum Testosterone levels (P<0.001), testicular GSH levels (P<0.001), motility of sperm (P<0.001), concentration of sperm (P<0.001), absolute ventral prostate (P<0.001) and absolute seminal vesicles (P<0.05) organ weight in Methotrexate + B. serrata group. The decrease in testicular MDA levels (P>0.05) and the increase in GSH–Px enzyme activity of testes (P>0.05) and final body weight (P>0.05) were not significant in Methotrexate + B. serrata group compared to the Methotrexate group. In conclusion, the negative effects of Methotrexate on the male reproductive system can be reduced by administering B. serrata extract.

Reproductive toxicity of JJH201501 in rats: Perinatal study

AbstractIntroductionIn this study, JJH201501 was examined for reproductive toxicity during the perinatal period to support its safety as a novel serotonergic agent (5‐HT) antidepressant. Pregnant Sprague–Dawley rats (F0, n = 24/group) were continuously exposed to 0 (control), 6, 18, and 60 mg/kg body weight/day of JJH201501 by intragastric administration from gestation day 15 to lactation day 21.MethodsDuring this period, maternal toxicity was evaluated based on clinical signs, body weight, feed intake, delivery condition, litter parameters, and necropsy, with body weight, sex ratios, malformation incidence, physical, and neurodevelopmental assessments conducted on all offspring rats. Ten pups (male:female 1:1) from each dam within each dose group on postnatal day 4 (PND4) were randomly selected. One pair was evaluated for behavior evaluations (F1a) after PND35, one for reproduction performance (F1b) after 10 weeks, and three for organ weight and deformities (F1c) on PND35. After successful mating, F1b male rats were weighed and dissected to assess reproductive organ weight and sperm motility. Pregnant F1b rats were weighed and monitored for food intake twice weekly until laparotomy on GD14, which recorded live/dead fetuses, resorptions, implantations, corpora lutea, and uterine weight. Some statistical differences were found between the JJH‐treated and control groups in maternal weight, food consumption, and F1 body weight and water maze performance.ResultsAutopsy results showed that JJH201501 had a low cardiac index effect in F0, with no significant histopathological changes detected. Only one F1 offspring died in the high‐dose group throughout the experiment. Due to the lack of dose‐dependent effects and the consistent growth pattern of these alterations, the study findings do not suggest any toxicological significance for the observed results.ConclusionIn conclusion, the no‐observed‐adverse‐effect level of JJH201501 for perinatal rats is about 60 mg/kg b.w./day.

Evaluating the effects of quinestrol on the reproductive organs of the Nile rat (Arvicanthis niloticus) for use in the rat control

ABSTRACTThe purpose of this research was to determine whether the synthetic estrogen quinestrol has antifertility effects on male and female Nile rats (Arvicanthis niloticus). Both male and female rats were orally administered quinestrol dissolved in castor oil at a dosage of 1 mg/kg for seven days. In contrast, male and female control rats were given castor oil alone. The use of this dosage of quinestrol resulted in a decrease in the weight of reproductive organs in both sexes, as well as a decrease in sperm count and motility and an increase in the percentage of abnormal sperm. Various histopathological alterations were observed in the testicular, epididymal, and ovarian tissues. Significant reductions in immunohistochemical markers such as androgen receptor protein (AR) and Wilm’s tumor nuclear protein 1 (Wt-1) were observed in treated male rats. These results indicate that quinestrol induces infertility in both males and females of the Nile rats. Therefore, it is recommended for use in integrated pest management campaigns targeting these serious vertebrate pests.