Research Fellow at Sathyabama University, INDIA /From the University of Dschang, CAMEROON


The methanol extract of Guibourtia tessmannii improves reproductive performances in obese male rat

Male infertility is a well-known complication resulting from obesity. Even though infertility is not a deadly disease it causes unpleasant feelings such as anger, frustration and depression particularly in developing countries patients. However, because of the multiple side effects experienced with the use of modern techniques for the treatment of male infertility, some people have opted for phytotherapy which has almost no side effects and a broader therapeutic spectrum.

Guibourtia tessmannii, is a plant used in Cameroon traditional medicine as an aphrodisiac. The main objective of this study was to evaluate the effects of the methanol extract of G. tessmannii on some fertility parameters in obese sexually sluggish male rats. Adult male Wistar rats were fed either with a 15 % palm oil diet (POD) or a standard diet (SD) for 16 weeks. At the end of the feeding period, obese-sexually sluggish rats were selected and treated for 7, 21 or 56 days. Further, the effects of the plant extract were evaluated on copulatory activity, sperm and biochemical parameters.

Palm oil diet-induced obesity impaired male rat reproductive performance. The methanol extract of G. tessmannii improved sexual parameters by increasing the mount, intromission and ejaculatory frequencies as well as sperm motility, viability, normality and count after 7, 21 or 56 days of treatment. Low density lipoprotein cholesterol and triglyceride levels were significantly lower in rats treated with plant extract while high density lipoprotein HDL cholesterol and testosterone levels in plasma and testis were significantly increased in the same group.

In conclusion, the results of the present study show that G. tessmannii possesses a pro-sexual effect in obese sexually sluggish rats. These findings may justify the ethno-medicinal use of G. tessmannii as a reproductive performance enhancer.


The impact of bariatric surgery on obesity-related infertility and in vitro fertilization outcomes.

Abstract: Obesity-related infertility is one of the most common problems of reproductive-age obese women who desire childbearing. The various types of bariatric surgeries have proved effective in controlling excessive weight gain, improving fertility, and preventing certain maternal and fetal complications in these women. This article summarizes the current evidence regarding the impact of bariatric surgery on obesity-related infertility and in vitro fertilization (IVF) outcomes. We have also attempted to draw conclusions about maternal and fetal risks and the benefits of bariatric surgery. Laparoscopic adjustable gastric banding and Roux-en-Y procedures are the two most commonly performed bariatric surgeries. Bariatric surgery was believed to improve menstrual irregularity and increase ovulation rate in anovulatory obese women, which lead to increased pregnancy rates. Although there are data in the literature suggesting the improvement of both the ovulatory function and the spontaneous pregnancy rates in obese women who lost weight after bariatric surgery, most of these are case-control studies with a small number of patients. The data are insufficient to determine an ideal time interval for pregnancy after bariatric surgery; however, the general consensus is that pregnancy should be delayed 12 to 18 months after bariatric surgery to avoid nutritional deficiencies. Few data exist regarding IVF success rates in women who have undergone bariatric surgery. One pairwise study discussed five patients who underwent bariatric surgery followed by IVF that resulted in three term pregnancies in three patients after the first IVF cycle. Many studies reported reductions in obesity-related pregnancy complications such as gestational diabetes and hypertensive disorders after bariatric surgery. Although data are inconsistent, some studies reported increased rate of preterm delivery and small for gestational age infants after bariatric surgery. Pregnancies after bariatric surgery may be considered high risk due to the concerns for vitamin deficiencies and gastrointestinal symptoms related to the surgery. Therefore the follow-up of these pregnancies might require a team approach including a maternal fetal medicine specialist, bariatric surgeon, and nutritionist.

Pub.: 18 Oct '12, Pinned: 24 Oct '17

Obesity-induced infertility and hyperandrogenism are corrected by deletion of the insulin receptor in the ovarian theca cell.

Abstract: Women with polycystic ovary syndrome (PCOS) exhibit elevated androgen levels, oligoanovulation, infertility, and insulin resistance in metabolic tissues. The aims of these studies were to determine the role of insulin signaling in the development and function of ovarian theca cells and the pathophysiologic effects of hyperinsulinism on ovarian function in obesity. We disrupted the insulin receptor (IR) gene specifically in the theca-interstitial (TI) cells of the ovaries (Cyp17IRKO). No changes in reproductive development or function were observed in lean Cyp17IRKO female mice, suggesting that insulin signaling in TI cell is not essential for reproduction. However, when females were fed a high-fat diet, diet-induced obesity (DIO) wild-type (DIO-WT) mice were infertile and experienced increased circulating testosterone levels, whereas DIO-Cyp17IRKO mice exhibited improved fertility and testosterone levels comparable to those found in lean mice. The levels of phosphorylated IRS1 and CYP17 protein were higher in the ovary of DIO-WT compared with DIO-Cyp17IRKO or lean mice. Ex vivo studies using a whole ovary culture model demonstrated that insulin acts independently or additively with human chorionic gonadotropin to enhance androstenedione secretion. These studies reveal the causal pathway linking hyperinsulinism with ovarian hyperandrogenism and the infertility of obesity.

Pub.: 01 Jan '14, Pinned: 24 Oct '17

Association of obesity with hormonal imbalance in infertility: a cross-sectional study in north Indian women.

Abstract: Hormones play an important role in the development and regulation of reproductive function and the menstrual cycle of women. Extremes of body weight tend to affect the homeostasis of the hypothalamo-pituitary-gonadal axis. This cross-sectional study was carried out in 113 women (57 with primary infertility and 56 with secondary infertility) in the age group 20-35 years, presenting for hormonal evaluation of infertility in a tertiary care hospital. After preliminary clinical evaluation, anthropometric indices (height, weight, BMI, waist circumference and waist hip ratio) were measured in all subjects. Fasting blood sample drawn on second/third day of menstrual cycle was analysed for serum luteinizing hormone, follicle stimulating hormone (FSH), prolactin and thyroid stimulating hormone (TSH). Serum FSH levels showed a significant positive correlation with indicators of central obesity (waist circumference and waist hip ratio in both the study groups). In primary infertility, significant positive correlation was also observed between serum FSH levels and other markers of obesity like body weight, hip circumference and BMI. In secondary infertility, serum prolactin and serum TSH levels demonstrated a significant positive correlation with body weight and BMI. Obesity is associated with hormonal derangements which are responsible for infertility. In overweight women with infertility, weight loss should be considered as a first line treatment.

Pub.: 16 Jan '14, Pinned: 24 Oct '17

Clinically relevant known and candidate genes for obesity and their overlap with human infertility and reproduction.

Abstract: Obesity is a growing public health concern now reaching epidemic status worldwide for children and adults due to multiple problems impacting on energy intake and expenditure with influences on human reproduction and infertility. A positive family history and genetic factors are known to play a role in obesity by influencing eating behavior, weight and level of physical activity and also contributing to human reproduction and infertility. Recent advances in genetic technology have led to discoveries of new susceptibility genes for obesity and causation of infertility. The goal of our study was to provide an update of clinically relevant candidate and known genes for obesity and infertility using high resolution chromosome ideograms with gene symbols and tabular form.We used computer-based internet websites including PubMed to search for combinations of key words such as obesity, body mass index, infertility, reproduction, azoospermia, endometriosis, diminished ovarian reserve, estrogen along with genetics, gene mutations or variants to identify evidence for development of a master list of recognized obesity genes in humans and those involved with infertility and reproduction. Gene symbols for known and candidate genes for obesity were plotted on high resolution chromosome ideograms at the 850 band level. Both infertility and obesity genes were listed separately in alphabetical order in tabular form and those highlighted when involved with both conditions.By searching the medical literature and computer generated websites for key words, we found documented evidence for 370 genes playing a role in obesity and 153 genes for human reproduction or infertility. The obesity genes primarily affected common pathways in lipid metabolism, deposition or transport, eating behavior and food selection, physical activity or energy expenditure. Twenty-one of the obesity genes were also associated with human infertility and reproduction. Gene symbols were plotted on high resolution ideograms and their name, precise chromosome band location and description were summarized in tabular form.Meaningful correlations in the obesity phenotype and associated human infertility and reproduction are represented with the location of genes on chromosome ideograms along with description of the gene and position in tabular form. These high resolution chromosome ideograms and tables will be useful in genetic awareness and counseling, diagnosis and treatment to improve clinical outcomes.

Pub.: 30 Jan '15, Pinned: 24 Oct '17

Male obesity is associated with changed spermatozoa Cox4i1 mRNA level and altered seminal vesicle fluid composition in a mouse model.

Abstract: The rate of obesity among men of reproductive age has tripled in the last three decades. Previously, we demonstrated that paternal obesity resulted in impaired preimplantation developmental kinetics, compromised post-compaction metabolism and decreased blastocyst cell number when embryos were generated in vivo. Subsequently, using in vitro fertilization we found embryos of obese males to have altered metabolism before compaction, reduced inner cell mass cell number and retarded fetal development--the difference between these two studies being the method of embryo generation and the presence or absence of seminal plasma, respectively. Here, we hypothesize that both sperm and seminal plasma are affected by obesity, compromising embryogenesis and pregnancy health in a cumulative manner. Epididymal sperm and seminal vesicle fluid were collected from normal and obese C57BL/6 mice. RNA and DNA were extracted from spermatozoa for qPCR and global methylation analysis, respectively. Proteomic (Luminex) and metabolomic (GC-MS) techniques were employed to analyse the composition of seminal vesicle fluid. Nuclear encoded cytochrome c oxidase subunit IV isoform 1 (Cox4i1) of the terminal enzyme in the mitochondrial respiratory chain demonstrated significantly increased RNA levels in the sperm of obese males (P< 0.05). Quantitative seminal plasma analysis identified significant changes in levels of the hormones insulin, leptin and estradiol between normal and obese males (P < 0.05). Further, the metabolite composition of seminal vesicle fluid was significantly affected by obesity. Consequently, this study has determined that obesity affects both sperm and seminal plasma composition. The interaction between sperm and seminal plasma warrants further analysis.

Pub.: 04 Mar '15, Pinned: 24 Oct '17

Mechanisms linking obesity to male infertility.

Abstract: Obesity in men is associated with infertility in numerous studies. The current trend for decline in semen parameters parallels the increasing prevalence of obesity worldwide. In addition to impaired semen quality, fertility among obese men may be affected by sexual dysfunction, endocrinopathy, aromatization activity, psychological and thermal effects, sleep apnea, leptin and minor toxins, and possibly the inflammatory and obstructive elements of epididymitis pathology. The variable degrees of certainty associated with these causes parallel the levels of supporting evidence. This search aims to shed lights on different conditions that obese men suffer from; as that makes the treatment of infertility more categorized.A PubMed search was conducted to identify clinical and pathological mechanisms linking obesity to male infertility.Among the myriad of publications reviewed in this paper, impaired spermatogenesis and sexual dysfunction have been shown to drive other variables towards poor fertility potentials. The paper presented a new, detailed flow chart showing more factors and further interactions among conditions leading to infertility.The prime hormonal defect in obese men is hypotestosteronaemia, which results in impaired spermatogenesis leading to poor fecundability. Studies have shown that most mechanisms accounting for reduced fertility potentials in overweight men are reversible.

Pub.: 29 Apr '15, Pinned: 24 Oct '17

Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility?

Abstract: Human feeding behavior and lifestyle are gradually being altered, favoring the development of metabolic diseases, particularly type 2 diabetes and obesity. Leptin is produced by the adipose tissue acting as a satiety signal. Its levels have been positively correlated with fat mass and hyperleptinemia has been proposed to negatively affect male reproductive function. Nevertheless, the molecular mechanisms by which this hormone affects male fertility remain unknown. Herein, we hypothesize that leptin acts on human Sertoli cells (hSCs), the "nurse cells" of spermatogenesis, altering their metabolism. To test our hypothesis, hSCs were cultured without or with leptin (5, 25 and 50ng/mL). Leptin receptor was identified by qPCR and Western blot. Protein levels of glucose transporters (GLUT1, GLUT2 and GLUT3), phosphofructokinase, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 (MCT4) were determined by Western Blot. LDH activity was assessed and metabolite production/consumption determined by proton nuclear magnetic resonance. Oxidative damage was evaluated by assessing lipid peroxidation, protein carbonilation and nitration. Our data shows that leptin receptor is expressed in hSCs. The concentration of leptin found in lean, healthy patients, upregulated GLUT2 protein levels and concentrations of leptin found in lean and obese patients increased LDH activity. Of note, all leptin concentrations decreased hSCs acetate production illustrating a novel mechanism for this hormone action. Moreover, our data shows that leptin does not induce or protect hSCs from oxidative damage. We report that this hormone modulates the nutritional support of spermatogenesis, illustrating a novel mechanism that may be linked to obesity-induced male infertility.

Pub.: 15 Jun '15, Pinned: 24 Oct '17

Leptin-Induced CART (Cocaine- and Amphetamine-Regulated Transcript) Is a Novel Intraovarian Mediator of Obesity-Related Infertility in Females.

Abstract: Obesity is considered detrimental to women's reproductive health. Although most of the attention has been focused on the effects of obesity on hypothalamic function, studies suggest a multifactorial impact. In fact, obesity is associated with reduced fecundity even in women with regular cycles, indicating that there may be local ovarian effects modulating fertility. Here we describe a novel mechanism for leptin actions directly in the ovary that may account for some of the negative effects of obesity on ovarian function. We find that normal cycling, obese, hyperleptinemic mice fed with a high-fat diet are subfertile and ovulate fewer oocytes compared with animals fed with a normal diet. Importantly, we show that leptin induces expression of the neuropeptide cocaine- and amphetamine-regulated transcript (CART) in the granulosa cells (GCs) of ovarian follicles both in vitro and in vivo. CART then negatively affects intracellular cAMP levels, MAPK signaling, and aromatase mRNA expression, which leads to lower estradiol synthesis in GCs and altered ovarian folliculogenesis. Finally, in human samples from patients undergoing in vitro fertilization, we show a significant positive correlation between patient body mass index, CART mRNA expression in GCs, and CART peptide levels in follicular fluid. These observations suggest that, under obese conditions, CART acts as a local mediator of leptin in the ovary to cause ovarian dysfunction and reduced fertility.

Pub.: 06 Jan '16, Pinned: 24 Oct '17

Protective effect of resveratrol on spermatozoa function in male infertility induced by excess weight and obesity.

Abstract: Male infertility is a complex, multifactorial and polygenic disease that contributes to ~50% cases of infertility. Previous studies have demonstrated that excess weight and obesity factors serve an important role in the development of male infertility. An increasing number of studies have reported that resveratrol may regulate the response of cells to specific stimuli that induce cell injury, as well as decrease germ cell apoptosis in mice or rats. In the present study, the semen quality and serum sex hormone levels were evaluated in 324 men, which included 73 underweight, 82 normal weight, 95 overweight and 74 obese men. All patients were referred to The Reproductive Medicine Center of Shanxi Women and Infants Hospital (Taiyuan, China) between January 2013 and January 2015. The aim of the present study was to investigate the effects of resveratrol treatment on the motility, plasma zinc concentration and acrosin activity of sperm from obese males. The sperm concentration, normal sperm morphology, semen volumes, DNA fragmentation rates and testosterone levels in men from the overweight and obese groups were markedly decreased when compared with men in the normal weight group. In addition, the progressive motility, seminal plasma zinc concentration and spermatozoa acrosin activity were notably decreased in the obese group compared with the normal weight group. However, estradiol levels were significantly increased in the overweight, obese and underweight groups compared with the normal weight group. Notably, semen samples from obese males with astenospermia treated with 0‑100 µmol/l resveratrol for 30 min demonstrated varying degrees of improvement in sperm motility. When these semen samples were treated with 30 µmol/l resveratrol, sperm motility improved when compared to other doses of resveratrol. Therefore, 30 µmol/l resveratrol was selected for further experiments. Upon treatment of semen samples with resveratrol (30 µmol/l) for 30 min, the seminal plasma zinc concentration and spermatozoa acrosin activity increased significantly in the experimental group compared with the control group. These data suggest that male obesity negatively impacts on male reproductive potential, not only through altering hormone levels, but also by directly altering sperm function. In addition, resveratrol may have a therapeutic and protective effect against obesity-induced abnormalities in semen.

Pub.: 18 Oct '16, Pinned: 24 Oct '17

Obesity and female infertility: potential mediators of obesity's impact.

Abstract: The worldwide upward trend in obesity has been dramatic, now affecting more than 20% of American women of reproductive age. Obesity is associated with many adverse maternal and fetal effects prenatally, but it also exerts a negative influence on female fertility. Obese women are more likely to have ovulatory dysfunction due to dysregulation of the hypothalamic-pituitary-ovarian axis. Women with polycystic ovarian syndrome who are also obese demonstrate a more severe metabolic and reproductive phenotype. Obese women have reduced fecundity even when eumenorrheic and demonstrate poorer outcomes with the use of in vitro fertilization. Obesity appears to affect the oocyte and the preimplantation embryo, with disrupted meiotic spindle formation and mitochondrial dynamics. Excess free fatty acids may have a toxic effect in reproductive tissues, leading to cellular damage and a chronic low-grade inflammatory state. Altered levels of adipokines, such as leptin, in the obese state can affect steroidogenesis and directly affect the developing embryo. The endometrium is also susceptible, with evidence of impaired stromal decidualization in obese women. This may explain subfecundity due to impaired receptivity, and may lead to placental abnormalities as manifested by higher rates of miscarriage, stillbirth, and preeclampsia in the obese population. Many interventions have been explored to mitigate the effect of obesity on infertility, including weight loss, physical activity, dietary factors, and bariatric surgery. These data are largely mixed, with few high quality studies to guide us. As we improve our understanding of the pathophysiology of obesity in human reproduction we hope to identify novel treatment strategies.

Pub.: 16 Mar '17, Pinned: 24 Oct '17

Obesity and male infertility.

Abstract: The prevalence of obesity has risen steadily for the past 35 years and presently affects more than a third of the US population. A concurrent decline in semen parameters has been described, and a growing body of literature suggests that obesity contributes to the male infertility. The purpose of this review is to examine the effects of obesity on male fertility, the mechanisms by which impaired reproductive health arise, and the outcomes of treatment.Obesity alters the hypothalamic-pituitary-gonadal axis both centrally and peripherally, resulting in hypogonadotropic, hyperestrogenic hypogonadism. Adipose tissue-derived factors, like leptin and adipokines, regulate testosterone production and inflammation, respectively. Increased systemic inflammation results in increased reactive oxygen species and sperm DNA fragmentation. Increased testicular temperature because of body habitus and inactivity impairs spermatogenesis. The degree to which obesity affects hormone levels, semen parameters, sperm DNA integrity, and pregnancy rates is variable, which may be the result of other comorbid conditions. Treatment in the form of weight loss has also had inconsistent results.Multiple interdependent mechanisms contribute to the detrimental effect of obesity on male fertility. Large, randomized control trials are needed to better characterize the therapeutic benefits of weight loss to restore male reproductive potential.

Pub.: 01 Jul '17, Pinned: 24 Oct '17

Assessment of the Effects of Graded Doses of Polyphenolic-Rich Fraction of Garcinia kola Seeds on Pituitary-Testicular Axis of Male Wistar Rats.

Abstract: This study evaluated the ameliorative and prophylactic effects of 2 different doses of polyphenolic-rich fraction of Garcinia kola (PPRFGk) seeds on the histology and hormones of pituitary-testicular axis of male Wistar rats. Thirty-five male Wistar rats (150-200 g) were divided into 7 groups of 5 rats each. Groups I and II were given distilled water (0.5 mL/day) for 8 days followed by propylene glycol (0.2 mL/d) and 600 mg/kg of PPRFGk, respectively, for 21 days. Group III received sodium arsenate (8 days), left untreated for 21 days. Groups IV and V received sodium arsenate (20 mg/kg) for 8 days followed by PPRFGk (300 and 600 mg/kg, respectively) for 21 days. Groups VI and VII received PPRFGk (300 and 600 mg/kg, respectively) for 21 days followed by sodium arsenate (20 mg/kg) for 8 days. Rats were killed by cervical dislocation 24 hours after the last dose and their blood collected through cardiac puncture. Blood sera were assayed for the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone using immunoassay techniques. Histology of the pituitary gland and testes was carried out. A significant reduction was observed in the concentration of FSH in groups IV, V, VI, and VII in comparison with groups I and II. The concentrations of both LH and testosterone showed significant decreases in groups IV, V, VI, and VII in comparison with group I. Group III presented with the lowest serum hormonal concentrations. Photomicrographs of the pituitary gland revealed greatly reduced basophils in group III and mildly reduced basophils in groups IV, VI, and VII in comparison with groups I and II. Group V revealed hypercellularized and distorted basophils. Photomicrographs of the testes showed detachment of the seminiferous tubules from the basement membrane and disruption of the interstitial space which was worse in group III, moderate in groups V and VI, and mild in group VII. In conclusion, PPRFGk effected a dose-dependent reversal and prevention of the perturbations caused by arsenate in rats.

Pub.: 21 Oct '17, Pinned: 24 Oct '17

The effects of ovariectomy and lifelong high-fat diet consumption on body weight, appetite, and lifespan in female rats.

Abstract: In females, ovarian hormones play pivotal roles in metabolic, appetite, and body weight regulation. In addition, it has been reported that ovarian hormones also affect longevity in some species. Recently, it was found that the consumption of a high-fat diet aggravates ovariectomy-associated metabolic dysregulation in female rodents. The aim of this study was to investigate the hypothesis that long-term high-fat diet consumption and ovariectomy interact to worsen body weight regulation and longevity in female rats. At 21days of age, female rats were weaned and randomly divided into two groups, one of which was given the high-fat diet, and the other was supplied with standard chow. At 23weeks of age, each group was further divided into ovariectomized and sham-operated groups, and then their body weight changes, food intake, and longevity were measured until 34months of age. The sham - high-fat diet rats exhibited greater body weight changes and higher feed efficiency than the sham - standard chow rats. On the other hand, the ovariectomized - high-fat diet and ovariectomized - standard chow rats displayed similar body weight changes and feed efficiency. The sham - high-fat diet and ovariectomized - standard chow rats demonstrated similar body weight changes and feed efficiency, indicating that the impact of ovariectomy on the regulation of body weight and energy metabolism might be similar to that of high-fat diet. Contrary to our expectations, ovariectomy and high-fat diet consumption both had small favorable effects on longevity. As the high-fat diet used in the present study not only had a high fat content, but also had a high caloric content and a low carbohydrate content compared with the standard chow, it is possible that the effects of the high-fat diet on body weight and longevity were partially induced by its caloric/carbohydrate contents. These findings indicate that the alterations in body weight and energy metabolism induced by ovariectomy and high-fat diet might not directly affect the lifespan of female rats.

Pub.: 22 Oct '17, Pinned: 24 Oct '17

Podophyllotoxin Extracted from Juniperus sabina Fruit Inhibits Rat Sperm Maturation and Fertility by Promoting Epididymal Epithelial Cell Apoptosis.

Abstract: This study aimed to investigate the antifertility effect of Juniperus sabina fruit on male rats and its possible mechanism, and hence it might be developed as a potential nonhormonal male contraceptive. Male rats were intragastrically fed for consecutive 8-week and 4-week recovery with the fruit of J. Sabina, and sperm maturation, serum testosterone level, and histopathology were analyzed. Epididymal epithelial cell culture was prepared for detection of podophyllotoxin activities. Furthermore, cell proliferation, transmission electron microscopy, Annexin V/Propidium iodide, TUNEL, RT-PCR, ELISA, and western blotting were examined. The results showed that rat sperm motility and fertility were remarkably declined after feeding the fruit. Moreover, the fruit targeted the epididymis rather than the testis. After 4-week recovery, more than half of the male rats resumed normal fertility. It was found that podophyllotoxin significantly inhibited epididymal epithelial cell proliferation, promoted cell apoptosis, and increased the mRNA and protein levels of TNF-α and the expression levels of cytochrome c, caspase-8, caspase-9, and caspase-3. Our findings suggest that the fruit of J. sabina could inhibit male rat sperm maturation and fertility. The potential mechanism might be related to podophyllotoxin, inducing epididymal epithelial cell apoptosis through TNF-α and caspase signaling pathway.

Pub.: 27 Jul '17, Pinned: 24 Oct '17