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Polar Quassinoids in Standardized Eurycoma longifolia Extract Formulated into a Lipid-Based Solid Dispersion to Improve Rat Sperm Count

Ma HQ, Ebrahimi F, Low BS, Khan NAK, Chan KL

Phytother Res, 2017 Dec;31(12):1875-1882.
PMID: 28948658 DOI: 10.1002/ptr.5930

Eurycoma longifolia Jack is popularly sought in Southeast Asian countries for traditional remedies to improve sexual performance and fertility. 13α(21)-Epoxyeurycomanone and eurycomanone, two major quassinoids in a root extract (TAF2) were reported to improve rat spermatogenesis and fertility. Unfortunately, these quassinoids possess low bioavailability because of high aqueous solubility and low lipid membrane permeability. Often, other possible barriers may be P-glycoprotein (P-gp) efflux in the gut and presystemic hepatic metabolism. The present study attempted to solve these problems by formulating a lipid-based solid dispersion (TAF2-SD) of optimized mixture of TAF2 and emulsifiers, which was then orally administered to rats prior to sperm count analysis. The TAF2-SD-treated rats showed significantly twofold (p

Matched MeSH terms: Spermatozoa/pathology
Exogenous leptin administration decreases sperm count and increases the fraction of abnormal sperm in adult rats

Haron MN, D'Souza UJ, Jaafar H, Zakaria R, Singh HJ

Fertil Steril, 2010 Jan;93(1):322-4.
PMID: 19709655 DOI: 10.1016/j.fertnstert.2009.07.995

Daily intraperitoneal injection of 5-30 microg/kg body weight of leptin for 42 days to adult rats decreases sperm count and increases the fraction of abnormal sperm.

Matched MeSH terms: Spermatozoa/pathology
Dermal exposure to the herbicide-paraquat results in genotoxic and cytotoxic damage to germ cells in the male rat

D'Souza UJ, Narayana K, Zain A, Raju S, Nizam HM, Noriah O

Folia Morphol (Warsz), 2006 Feb;65(1):6-10.
PMID: 16783728

The effects of exposure to low doses of paraquat, a herbicide, via the dermal route were studied on the spermatozoa of Sprague-Dawley rats. Paraquat (1, 1'-dimethyl-4, 4'-bipyridinium dichloride) was administered once a day for five days, at intervals of 24 h at 0, 6, 15 and 30 mg/kg, and the rats were sacrificed on days 7, 14, 28, and 42 after the last exposure. The sperm suspensions were obtained by mincing the caudae epididymes and ductus deferens for the purpose of performing a sperm morphology test, sperm count and analysis of sperm mortality and sperm motility, as per the standard procedures. The sperm count was decreased (p < 0.05) only on days 7 and 14 but sperm abnormalities increased on all days (p < 0.05). Sperm mortality increased at higher dose-levels (p < 0.05) except on day 42, and motility was affected by 30 mg/kg only on day 42. In conclusion, paraquat is a genotoxic and cytotoxic agent to germ cells in the male rat.

Matched MeSH terms: Spermatozoa/pathology
Geographical differences in semen characteristics: Comparing semen parameters of infertile men of the United States and Iraq

Palani A, Sengupta P, Agarwal A, Henkel R

Andrologia, 2020 Apr;52(3):e13519.
PMID: 32003032 DOI: 10.1111/and.13519

The declining trend of male fecundity is a major global health and social concern. Among numerous other confounding factors, variations in male fertility parameters in different regions have repeatedly been suggested to be influenced by geographic locations. The impact of overall lifestyle, behavioural patterns, ethnicity, work stress and associated factors upon health differ greatly between developed and developing countries. These factors, individually or in combination, affect male reproductive functions ensuing the discrepancies in semen qualities in connection with geographic variations. However, reports comparing semen characteristics between developed and developing countries are sparse. The present study finds its novelty in presenting a comparison in semen parameters of infertile men in the United States (n = 76) that fairly represents the population of a highly developed region and Iraq (n = 102), the representative of male populations of a developing region. Samples were collected and analysed according to WHO (WHO laboratory manual for the examination and processing of human semen, WHO; 2010) criteria by means of the Mann-Whitney test. The US population demonstrated lower sperm concentration, total count, and total and progressive sperm motility with a higher seminal total antioxidant capacity (TAC) as compared to the Iraqi population. This report encourages further investigations concerning the confounding factors leading to such alterations in semen qualities between these two geographic areas.

Matched MeSH terms: Spermatozoa/pathology*
Reactive oxygen species-induced alterations in H19-Igf2 methylation patterns, seminal plasma metabolites, and semen quality

Darbandi M, Darbandi S, Agarwal A, Baskaran S, Dutta S, Sengupta P, et al.

J Assist Reprod Genet, 2019 Feb;36(2):241-253.
PMID: 30382470 DOI: 10.1007/s10815-018-1350-y

PURPOSE: This study was conducted in order to investigate the effects of reactive oxygen species (ROS) levels on the seminal plasma (SP) metabolite milieu and sperm dysfunction.
METHODS: Semen specimens of 151 normozoospermic men were analyzed for ROS by chemiluminescence and classified according to seminal ROS levels [in relative light units (RLU)/s/106 sperm]: group 1 (n = 39): low (ROS

Matched MeSH terms: Spermatozoa/pathology
Pre- and postnatal toxicity of diazinon induces disruption of spermatogenetic cell line evidenced by increased testicular marker enzymes activities in rat offspring

Jayachandra S, D'Souza UJ

J Environ Pathol Toxicol Oncol, 2013;32(1):73-90.
PMID: 23758154

The objective of this study was to study the possible reproductive adverse effects of the diazinon on rat offspring exposed in utero and during lactation. Dams were gavaged daily (10, 15, and 30 mg/kg) before mating, during mating, and during pregnancy and lactation in separate groups. Reproductive outcome data of dams were examined. Body weight, testis weight, testicular marker enzyme activities (alkaline phosphatase, acid phosphatase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase), qualitative and quantitative testicular and epididymal histology, and immunohistochemisty for 3-β-hydroxysteroid dehydrogenase (HSD) were examined in male offspring at puberty and adulthood. The 30-mg/kg dose induced significant adverse effects at both puberty and adulthood in offspring. At puberty the male offspring showed a decrease in testicular weight, degenerative changes, and 3-β-HSD. Moreover, an increase in activity of alkaline and acid phosphatase also was observed. At adulthood, there was a decrease in testicular weight and 3-β-HSD with an increase in the levels of testicular marker enzyme. There was evidence of some adverse reproductive effects in male offspring at the 15-mg/kg dose. Most of the adverse effects were irreversible and were evident at both puberty and adulthood in offspring, although a few parameters reverted back to the normal growth pattern. Hence, diazinon is a reproductive toxicant in male offspring, which caused significant damage to the testes when exposed during prenatal and postnatal life.

Matched MeSH terms: Spermatozoa/pathology
Proteomic Signatures of Sperm Mitochondria in Varicocele: Clinical Use as Biomarkers of Varicocele Associated Infertility

Samanta L, Agarwal A, Swain N, Sharma R, Gopalan B, Esteves SC, et al.

J Urol, 2018 08;200(2):414-422.
PMID: 29530785 DOI: 10.1016/j.juro.2018.03.009

PURPOSE: Varicocele may disrupt testicular microcirculation and induce hypoxia-ischemia related degenerative changes in testicular cells and spermatozoa. Superoxide production at low oxygen concentration exacerbates oxidative stress in men with varicocele. Therefore, the current study was designed to study the role of mitochondrial redox regulation and its possible involvement in sperm dysfunction in varicocele associated infertility.
MATERIALS AND METHODS: We identified differentially expressed mitochondrial proteins in 50 infertile men with varicocele and in 10 fertile controls by secondary liquid chromatography-tandem mass spectroscopy data driven in silico analysis. Identified proteins were validated by Western blot and immunofluorescence. Seminal oxidation-reduction potential was measured.
RESULTS: We identified 22 differentially expressed proteins related to mitochondrial structure (LETM1, EFHC, MIC60, PGAM5, ISOC2 and import TOM22) and function (NDFSU1, UQCRC2 and COX5B, and the core enzymes of carbohydrate and lipid metabolism). Cluster analysis and 3-dimensional principal component analysis revealed a significant difference between the groups. All proteins studied were under expressed in infertile men with varicocele. Liquid chromatography-tandem mass spectroscopy data were corroborated by Western blot and immunofluorescence. Impaired mitochondrial function was associated with decreased expression of the proteins (ATPase1A4, HSPA2, SPA17 and APOA1) responsible for proper sperm function, concomitant with elevated seminal oxidation-reduction potential in the semen of infertile patients with varicocele.
CONCLUSIONS: Impaired mitochondrial structure and function in varicocele may lead to oxidative stress, reduced ATP synthesis and sperm dysfunction. Mitochondrial differentially expressed proteins should be explored for the development of biomarkers as a predictor of infertility in patients with varicocele. Antioxidant therapy targeting sperm mitochondria may help improve the fertility status of these patients.

Matched MeSH terms: Spermatozoa/pathology