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Neither male age nor semen parameters influence clinical pregnancy or live birth outcomes from IVF

Mariappen U, Keane KN, Hinchliffe PM, Dhaliwal SS, Yovich JL

Reprod Biol, 2018 Dec;18(4):324-329.
PMID: 30503182 DOI: 10.1016/j.repbio.2018.11.003

Advanced age is an increasing trend for both males and females seeking in vitro fertilization (IVF). This retrospective cohort study investigated the outcomes of 1280 IVF-related treatment cycles, selecting the first treatment for couples utilizing autologous gametes and who underwent single fresh embryo transfer. Males aged 40-49 years had a 52% reduction in normal sperm motility, while it was markedly reduced by 79% at 50 years or older. However, neither semen parameters nor male age were predictive of clinical pregnancy or live birth chance. In a combination of age groups, cases with Younger Females had the greatest chance of successful outcomes and this was independent of having a younger or older male partner. Specifically, Young Female-Young Male combinations (≤ 35 years) were the most likely to succeed in achieving a clinical pregnancy or live birth (OR 2.84, p 35 years, respectively) had a similar increased chance (OR 2.07, p

Matched MeSH terms: Spermatozoa
Fulltext Evolutionary and functional analysis of RBMY1 gene copy number variation on the human Y chromosome

Shi W, Louzada S, Grigorova M, Massaia A, Arciero E, Kibena L, et al.

Hum Mol Genet, 2019 Aug 15;28(16):2785-2798.
PMID: 31108506 DOI: 10.1093/hmg/ddz101

Human RBMY1 genes are located in four variable-sized clusters on the Y chromosome, expressed in male germ cells and possibly associated with sperm motility. We have re-investigated the mutational background and evolutionary history of the RBMY1 copy number distribution in worldwide samples and its relevance to sperm parameters in an Estonian cohort of idiopathic male factor infertility subjects. We estimated approximate RBMY1 copy numbers in 1218 1000 Genomes Project phase 3 males from sequencing read-depth, then chose 14 for valid ation by multicolour fibre-FISH. These fibre-FISH samples provided accurate calibration standards for the entire panel and led to detailed insights into population variation and mutational mechanisms. RBMY1 copy number worldwide ranged from 3 to 13 with a mode of 8. The two larger proximal clusters were the most variable, and additional duplications, deletions and inversions were detected. Placing the copy number estimates onto the published Y-SNP-based phylogeny of the same samples suggested a minimum of 562 mutational changes, translating to a mutation rate of 2.20 × 10-3 (95% CI 1.94 × 10-3 to 2.48 × 10-3) per father-to-son Y-transmission, higher than many short tandem repeat (Y-STRs), and showed no evidence for selection for increased or decreased copy number, but possible copy number stabilizing selection. An analysis of RBMY1 copy numbers among 376 infertility subjects failed to replicate a previously reported association with sperm motility and showed no significant effect on sperm count and concentration, serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels or testicular and semen volume. These results provide the first in-depth insights into the structural rearrangements underlying RBMY1 copy number variation across diverse human lineages.

Matched MeSH terms: Spermatozoa/metabolism
Fulltext Comparison on the Effects and Safety of Tualang Honey and Tribestan in Sperm Parameters, Erectile Function, and Hormonal Profiles among Oligospermic Males

Ismail SB, Bakar MB, Nik Hussain NH, Norhayati MN, Sulaiman SA, Jaafar H, et al.

Evid Based Complement Alternat Med, 2014;2014:126138.
PMID: 25505918 DOI: 10.1155/2014/126138

Introduction. This study aims to evaluate the effectiveness of Tualang honey on sperm parameters, erectile function, and hormonal and safety profiles. Methodology. A randomized control trial was done using Tualang honey (20 grams) and Tribestan (750 mg) over a period of 12 weeks. Sperm parameters including sperm concentration, motility, and morphology were analyzed and erectile function was assessed using IIEF-5 questionnaire. Hormonal profiles of testosterone, FSH, and LH were studied. The volunteers were randomized into two groups and the outcomes were analyzed using SPSS version 18. Results. A total of 66 participants were involved. A significant increment of mean sperm concentration (P < 0.001), motility (P = 0.015) and morphology (P = 0.008) was seen in Tualang honey group. In Tribestan group, a significant increment of mean sperm concentration (P = 0.007), and morphology (P = 0.009) was seen. No significant differences of sperm concentration, motility, and morphology were seen between Tualang honey and Tribestan group and similar results were also seen in erectile function and hormonal profile. All safety profiles were normal and no adverse event was reported. Conclusion. Tualang honey effect among oligospermic males was comparable with Tribestan in improving sperm concentration, motility, and morphology. The usage of Tualang honey was also safe with no reported adverse event.

Matched MeSH terms: Spermatozoa
Afterword: An update on clinical utility and diagnostic value of various andrological techniques

Durairajanayagam D, Agarwal A, Baskaran S, Vij S

Andrologia, 2021 Mar;53(2):e13819.
PMID: 33620116 DOI: 10.1111/and.13819
Matched MeSH terms: Spermatozoa/metabolism
A proof of principal study on the use of direct PCR of semen and spermatozoa and development of a differential isolation protocol for use in cases of alleged sexual assault

Tobe SS, Swaran YC, Dennany L, Sibbing U, Schulze Johann K, Welch L, et al.

Int J Legal Med, 2017 Jan;131(1):87-94.
PMID: 27832353 DOI: 10.1007/s00414-016-1461-x

Sexual assault samples are some of the most common samples encountered in forensic analysis. These samples can require a significant time investment due to differential extraction processes. We report on the first record of successful direct amplification of semen for STR analysis. Neat seminal fluid, dilutions ranging from 1:5 to 1:160 and GEDNAP samples were successfully amplified using a direct method. A mild differential isolation technique to enrich spermatozoa was developed and successfully implemented to separate and directly amplify a mixture of semen and female epithelial cells. Aliquots of samples subjected to the differential isolation protocol were stained with Haemotoxylin and Eosin for sperm scoring. Samples stained after PCR showed a complete lack of intact spermatozoa demonstrating that the cells are lysed during the PCR process. This paper demonstrates the potential to incorporate direct PCR in cases of sexual assault to more rapidly obtain results and achieve a higher sensitivity.

Matched MeSH terms: Spermatozoa
Proteomics, oxidative stress and male infertility

Agarwal A, Durairajanayagam D, Halabi J, Peng J, Vazquez-Levin M

Reprod Biomed Online, 2014 Jul;29(1):32-58.
PMID: 24813754 DOI: 10.1016/j.rbmo.2014.02.013

Oxidative stress has been established as one of the main causes of male infertility and has been implicated in many diseases associated with infertile men. It results from high concentrations of free radicals and suppressed antioxidant potential, which may alter protein expression in seminal plasma and/or spermatozoa. In recent years, proteomic analyses have been performed to characterize the protein profiles of seminal ejaculate from men with different clinical conditions, such as high oxidative stress. The aim of the present review is to summarize current findings on proteomic studies performed in men with high oxidative stress compared with those with physiological concentrations of free radicals, to better understand the aetiology of oxidative stress-induced male infertility. Each of these studies has suggested candidate biomarkers of oxidative stress, among them are DJ-1, PIP, lactotransferrin and peroxiredoxin. Changes in protein concentrations in seminal plasma samples with oxidative stress conditions were related to stress responses and to regulatory pathways, while alterations in sperm proteins were mostly associated to metabolic responses (carbohydrate metabolism) and stress responses. Future studies should include assessment of post-translational modifications in the spermatozoa as well as in seminal plasma proteomes of men diagnosed with idiopathic infertility. Oxidative stress, which occurs due to a state of imbalance between free radicals and antioxidants, has been implicated in most cases of male infertility. Cells that are in a state of oxidative stress are more likely to have altered protein expression. The aim of this review is to better understand the causes of oxidative stress-induced male infertility. To achieve this, we assessed proteomic studies performed on the seminal plasma and spermatozoa of men with high levels of oxidative stress due to various clinical conditions and compared them with men who had physiological concentrations of free radicals. A variety of sperm and seminal plasma proteins were found to be expressed either in abundance (over-expressed) or in a lesser amount (underexpressed), while other proteins were found to be unique either to men with oxidative stress or to men with a balanced ratio of antioxidants/free radicals. Each study included in this review suggested several proteins that could possibly act as biomarkers of oxidative stress-induced male infertility, such as protein DJ-1, PIP, lactotransferrin and peroxiredoxin. Pathway analysis performed in these studies revealed that the changes in seminal plasma proteins in men with oxidative stress could be attributed to stress responses and regulatory pathways, while changes in sperm proteins were linked to stress responses and metabolic responses. Subsequent studies could look into post-translational modifications in the protein profile of men with idiopathic infertility. We hope that the information in this review will contribute to a better understanding of the main causes of idiopathic male infertility.

Matched MeSH terms: Spermatozoa/metabolism
Radio frequency electromagnetic radiation (RF-EMR) from GSM (0.9/1.8GHz) mobile phones induces oxidative stress and reduces sperm motility in rats

Mailankot M, Kunnath AP, Jayalekshmi H, Koduru B, Valsalan R

Clinics (Sao Paulo), 2009;64(6):561-5.
PMID: 19578660

INTRODUCTION: Mobile phones have become indispensable in the daily lives of men and women around the globe. As cell phone use has become more widespread, concerns have mounted regarding the potentially harmful effects of RF-EMR from these devices.
OBJECTIVE: The present study was designed to evaluate the effects of RF-EMR from mobile phones on free radical metabolism and sperm quality.
MATERIALS AND METHODS: Male albino Wistar rats (10-12 weeks old) were exposed to RF-EMR from an active GSM (0.9/1.8 GHz) mobile phone for 1 hour continuously per day for 28 days. Controls were exposed to a mobile phone without a battery for the same period. The phone was kept in a cage with a wooden bottom in order to address concerns that the effects of exposure to the phone could be due to heat emitted by the phone rather than to RF-EMR alone. Animals were sacrificed 24 hours after the last exposure and tissues of interest were harvested.
RESULTS: One hour of exposure to the phone did not significantly change facial temperature in either group of rats. No significant difference was observed in total sperm count between controls and RF-EMR exposed groups. However, rats exposed to RF-EMR exhibited a significantly reduced percentage of motile sperm. Moreover, RF-EMR exposure resulted in a significant increase in lipid peroxidation and low GSH content in the testis and epididymis.
CONCLUSION: Given the results of the present study, we speculate that RF-EMR from mobile phones negatively affects semen quality and may impair male fertility.

Matched MeSH terms: Spermatozoa/radiation effects
Fulltext Quantification of coral sperm collected during a synchronous spawning event

Teo A, Guest JR, Neo ML, Vicentuan K, Todd PA

PeerJ, 2016;4:e2180.
PMID: 27478697 DOI: 10.7717/peerj.2180

Most studies of coral reproductive biology to date have focused on oocyte numbers and sizes. Only one (ex situ) study has enumerated sperm numbers, even though these data have multiple potential applications. We quantified total coral sperm and eggs per gamete bundle collected from six species in situ during a synchronous spawning event in Singapore. Egg-sperm bundles were captured midwater as they floated towards the surface after being released by the colony. For each sample, a semi-transparent soft plastic bottle was squeezed and released to create a small suction force that was used to 'catch' the bundles. This technique provided several advantages over traditional methods, including low cost, ease of use, no diving prior to the night of collection needed, and the ability to target specific areas of the colony. The six species sampled were Echinophyllia aspera, Favites abdita, F. chinensis, Merulina ampliata, M. scabricula and Platygyra pini. The mean number of sperm packaged within one egg-sperm bundle ranged from 2.04 × 10(6) to 1.93 × 10(7). The mean number of eggs per egg-sperm bundle ranged from 26.67 (SE ± 3.27) to 85.33 (SE ± 17.79). These data are critical for fertilisation success models, but the collection technique described could also be applied to studies requiring in situ spawning data at the polyp level.

Matched MeSH terms: Spermatozoa
Light and the gonadal cycle of the black-headed Munia, Munia malacca malacca

Pandha SK, Thapliyal JP

Endocrinol. Jpn., 1969 Feb;16(1):157-61.
PMID: 5394323
Matched MeSH terms: Spermatozoa
Fulltext Effects of Melicope Ptelifolia aqueous extract on sperm parameters and testosterone level in Sprague-Dawley rats

Nazizarini Binti Mohd Najib, Perimal, Enoch Kumar, Mohd. Roslan Bin Sulaiman, Ahmad Akira Omar Farouk, Tengku Azam Shah Bin Tengku Mohamad

Life Sciences, Medicine and Biomedicine, 2018;2(4):1-6.
MyJurnal

The increasing number of prevalence infertility cases is becoming a major public health problem in developing countries due to changes in diet and lifestyle. Melicope ptelefolia (M.ptelifolia) is known for its health benefit as a sex enhancing effect among the Malays folk however there is no clinical data to prove it until these days. The main aim of the present study is to identify the effects of Melicope ptelifolia Aqueous extract (MPAE) on Sperm Parameters and Testosterone Level . A total of 30 male Sprague Dawley rats were divided equally into five different groups. MPAE was given by orally gavage for 28 days at a dose of 100mg/kg, 200 mg/kg and 500 mg/kg body weight to the animals of group II (n=6), III (n=6) and IV (n=6), respectively. The animals of group I (control, n=6) had distilled water and group V had sildenafil citrate. Sperm Parameters were carried include sperm count, motility, mobility and morphology together with serum testosterone level for Testosterone level result. Results were analyzed using one way ANOVA test followed by Tukey test and the data were considered significant at p

Matched MeSH terms: Spermatozoa
Treatment of the Hypogonadal Infertile Male-A Review

Ho CC, Tan HM

Sex Med Rev, 2013 May;1(1):42-49.
PMID: 27784559 DOI: 10.1002/smrj.4

INTRODUCTION: Testosterone treatment for hypogonadism is detrimental for men in reproductive age as it impairs spermatogenesis, and therefore affects fertility. It is, therefore, not indicated in men with hypogonadism and infertility.
AIM: The aim of this review is to analyze current data regarding options of treatment for men with hypogonadism and infertility.
MAIN OUTCOMES MEASURES: A comprehensive review of the current literature on management of infertility among hypogonadal men.
METHODS: A literature search using PubMed from 1980 to 2012 was done on articles published in the English language. The following medical subject heading terms were used: "infertility," "infertile," "hypogonadism;" "testosterone deficiency" and "men" or "male;" and "treatment" or "management."
RESULTS: The options for hypogonadal testicular failure are limited. Hormonal treatment is by and large ineffective. For secondary hypogonadism (hypogonadotropic/normogonadotropic hypogonadism), the options include gonadotropin-releasing hormone, human chorionic gonadotropin (hCG), human menopausal gonadotropin (hMG), follicle-stimulating hormone (FSH), and anti-estrogens and aromatase inhibitors. Dopamine antagonist is indicated for prolactinoma. Artificial reproductive technique is indicated for primary testicular failure and also when medical therapy fails.
CONCLUSION: The most suitable option with the current data available is hCG with or without hMG/FSH. Testosterone supplementation should be avoided, but if they are already on it, it is still possible for a return of normal sperm production within 1 year after discontinuing testosterone. Ho CCK and Tan HM. Treatment of the hypogonadal infertile male-A review. Sex Med Rev 2013;1:42-49.

Matched MeSH terms: Spermatozoa
Fulltext Role of Zinc (Zn) in Human Reproduction: A Journey from Initial Spermatogenesis to Childbirth

Vickram S, Rohini K, Srinivasan S, Nancy Veenakumari D, Archana K, Anbarasu K, et al.

Int J Mol Sci, 2021 Feb 22;22(4).
PMID: 33671837 DOI: 10.3390/ijms22042188

Zinc (Zn), the second-most necessary trace element, is abundant in the human body. The human body lacks the capacity to store Zn; hence, the dietary intake of Zn is essential for various functions and metabolism. The uptake of Zn during its transport through the body is important for proper development of the three major accessory sex glands: the testis, epididymis, and prostate. It plays key roles in the initial stages of germ cell development and spermatogenesis, sperm cell development and maturation, ejaculation, liquefaction, the binding of spermatozoa and prostasomes, capacitation, and fertilization. The prostate releases more Zn into the seminal plasma during ejaculation, and it plays a significant role in sperm release and motility. During the maternal, labor, perinatal, and neonatal periods, the part of Zn is vital. The average dietary intake of Zn is in the range of 8-12 mg/day in developing countries during the maternal period. Globally, the dietary intake of Zn varies for pregnant and lactating mothers, but the average Zn intake is in the range of 9.6-11.2 mg/day. The absence of Zn and the consequences of this have been discussed using critical evidence. The events and functions of Zn related to successful fertilization have been summarized in detail. Briefly, our current review emphasizes the role of Zn at each stage of human reproduction, from the spermatogenesis process to childbirth. The role of Zn and its supplementation in in vitro fertilization (IVF) opens opportunities for future studies on reproductive biology.

Matched MeSH terms: Spermatozoa/physiology
Improvement of sperm quality of the depik fish, rasbora tawarensis, after cryopreservation using antioxidant

Muchlisin ZA, Afriani D, Eriani K, Hasri I, Nur FM, Maulida S, et al.

Cryo Letters, 2022;44(1):13-19.
PMID: 36625871

BACKGROUND: The cryopreservation of the sperm of the depik fish, Rasbora tawarensis, has previously been developed. However, the quality of the sperm post cryopreservation was not satisfactory and might be improved through the application of antioxidants.
OBJECTIVE: To determine the most suitable antioxidant for the cryopreservation of the depik fish spermatozoa.
MATERIALS AND METHODS: A completely randomized design with a non-factorial experiment was used and the tested antioxidants were glutathione, beta-carotene, ascorbic acid, and butylated hydroxytoluene (BHT) at 6 % concentrations. All treatments had three replications. The sperms were collected from 10 male fishes and diluted with Ringer solution in a ratio of 1: 20 (v/v, sperm: Ringer solution). Then 5% DMSO and 5 % egg yolk were added to the diluted sperms. Furthermore, 6 % of the tested antioxidants were added to the diluents, and then, cryopreservation was carried out in liquid nitrogen for 14 days.
RESULTS: The ANOVA test showed that the application of antioxidants significantly affected the sperm motility, fertility, and hatching rates of the eggs (P < 0.05). Furthermore, the antioxidants also protected the sperm cells during cryopreservation, with glutathione being the best antioxidant.
CONCLUSION: The application of antioxidants during the cryopreservation of depik fish sperm had a significant effect on motility, fertility and hatchability of eggs post-cryo. Furthermore, glutathione was the most suitable antioxidant. doi.org/10.54680/fr23110110312.

Matched MeSH terms: Spermatozoa
Improvement of sperm quality of the depik fish, rasbora tawarensis, after cryopreservation using antioxidant

Muchlisin ZA, Afriani D, Eriani K, Hasri I, Nur FM, Maulida S, et al.

Cryo Letters, 2023;44(1):13-19.
PMID: 36629837

BACKGROUND: The cryopreservation of the sperm of the depik fish, Rasbora tawarensis, has previously been developed. However, the quality of the sperm post cryopreservation was not satisfactory and might be improved through the application of antioxidants.
OBJECTIVE: To determine the most suitable antioxidant for the cryopreservation of the depik fish spermatozoa.
MATERIALS AND METHODS: A completely randomized design with a non-factorial experiment was used and the tested antioxidants were glutathione, beta-carotene, ascorbic acid, and butylated hydroxytoluene (BHT) at 6 % concentrations. All treatments had three replications. The sperms were collected from 10 male fishes and diluted with Ringer solution in a ratio of 1: 20 (v/v, sperm: Ringer solution). Then 5% DMSO and 5 % egg yolk were added to the diluted sperms. Furthermore, 6 % of the tested antioxidants were added to the diluents, and then, cryopreservation was carried out in liquid nitrogen for 14 days.
RESULTS: The ANOVA test showed that the application of antioxidants significantly affected the sperm motility, fertility, and hatching rates of the eggs (P < 0.05). Furthermore, the antioxidants also protected the sperm cells during cryopreservation, with glutathione being the best antioxidant.
CONCLUSION: The application of antioxidants during the cryopreservation of depik fish sperm had a significant effect on motility, fertility and hatchability of eggs post-cryo. Furthermore, glutathione was the most suitable antioxidant. doi.org/10.54680/fr23110110312.

Matched MeSH terms: Spermatozoa
Fulltext First Evaluations and Cryopreservation of Semen Samples from Sunda Clouded Leopards (Neofelis diardi)

Zainuddin ZZ, Mohamed Tarmizi MR, Yap KC, Comizzoli P, Sipangkui S

Animals (Basel), 2020 06 22;10(6).
PMID: 32580372 DOI: 10.3390/ani10061072

A better understanding of semen characteristics and resilience to freezing temperatures is necessary before developing assisted reproductive techniques and systematic biobanking for the Sunda clouded leopard. The objective of this study was to evaluate for the first time the semen and sperm quality (in fresh and frozen samples) of two captive Sunda clouded leopards in Malaysia. A total of 17 examinations of the reproductive tract (using ultrasonography) and electro-ejaculations were performed on the two leopards over a 2-year period. Samples obtained from Leopard 1 (8 years old) varied in terms of volume (402 ± 92 µL), pH (7.9 ± 0.9), sperm motility (54.5 ± 24.2%), sperm concentration (122.4 ± 84.7 × 106 sperm/mL), normal morphology (23.9 ± 12.3%), and viability (55.2 ± 18.2%). Midpiece defects represented the most common structural abnormality followed by abnormal tail and head defects. Samples from Leopard 2 (11 year old with abnormal testicular tissue) were of lesser quality. Two frozen semen samples from Leopard 1 were thawed and examined for acrosome integrity. Post-thawed samples contained <10% of motile spermatozoa but almost 50% of abnormal acrosomes. The present results emphasized the high incidence of structurally-abnormal spermatozoa, similar to the mainland clouded leopard. Post-thaw evaluations showed that the few surviving spermatozoa could potentially be used for in vitro fertilization or sperm injection. However, more individuals must be studied to validate those first findings that are exciting but still preliminary.

Matched MeSH terms: Spermatozoa
Effects of leptin on sperm count and morphology in Sprague-Dawley rats and their reversibility following a 6-week recovery period

Almabhouh FA, Osman K, Siti Fatimah I, Sergey G, Gnanou J, Singh HJ

Andrologia, 2015 Sep;47(7):751-8.
PMID: 25269426 DOI: 10.1111/and.12325

Altered epididymal sperm count and morphology following leptin treatment has been reported recently. This study examined the effects of 42 days of leptin treatment on sperm count and morphology and their reversibility during a subsequent 56-day recovery period. Twelve-week-old male Sprague-Dawley rats were randomised into four leptin and four saline-treated control groups (n = 6). Intraperitoneal injections of leptin were given daily (60 μg Kg(-1) body weight) for 42 days. Controls received 0.1 ml of 0.9% saline. Leptin-treated animals and their respective age-matched controls were euthanised on either day 1, 21, 42 or 56 of recovery for collection of epididymal spermatozoa. Sperm concentration was determined using a Makler counting chamber. Spermatozoa were analysed for 8-hydroxy-2-deoxyguanosine and DNA fragmentation (Comet assay). Data were analysed using anova. Sperm concentration was significantly lower but fraction of abnormal spermatozoa, and levels of 8-hydroxy-2-deoxyguanosine were significantly higher in leptin-treated rats on day 1 of recovery. Comet assays revealed significant DNA fragmentation in leptin-treated rats. These differences were reduced by day 56 of recovery. It appears that 42 days of leptin treatment to Sprague-Dawley rats has significant adverse effects on sperm count and morphology that reverse following discontinuation of leptin treatment.

Matched MeSH terms: Spermatozoa/drug effects*
Fulltext Melatonin ameliorates the adverse effects of leptin on sperm

Almabhouh FA, Osman K, Ibrahim SF, Gupalo S, Gnanou J, Ibrahim E, et al.

Asian J Androl, 2016 10 18;19(6):647-654.
PMID: 27748315 DOI: 10.4103/1008-682X.183379

This study examined the effects of melatonin on leptin-induced changes in sperm parameters in adult rats. Five groups of Sprague-Dawley rats were treated with either leptin or leptin and melatonin or melatonin for 6 weeks. Leptin was given daily via the intraperitoneal route (60 μg kg-1 body weight) and melatonin was given in drinking water (10 mg kg-1 or 20 mg kg-1 body weight per day). Upon completion, sperm count, sperm morphology, 8-hydroxy-2-deoxyguanosine, Comet assay, TUNEL assay, gene expression profiles of antioxidant enzymes, respiratory chain reaction enzymes, DNA damage, and apoptosis genes were estimated. Data were analyzed using ANOVA. Sperm count was significantly lower whereas the fraction of sperm with abnormal morphology, the level of 8-hydroxy-2-deoxyguanosine, and sperm DNA fragmentation were significantly higher in rats treated with leptin only. Microarray analysis revealed significant upregulation of apoptosis-inducing factor, histone acetyl transferase, respiratory chain reaction enzyme, cell necrosis and DNA repair genes, and downregulation of antioxidant enzyme genes in leptin-treated rats. Real-time polymerase chain reaction showed significant decreases in glutathione peroxidase 1 expression with increases in the expression of apoptosis-inducing factor and histone acetyl transferase in leptin-treated rats. There was no change in the gene expression of caspase-3 (CASP-3). In conclusion, the adverse effects of leptin on sperm can be prevented by concurrent melatonin administration.

Matched MeSH terms: Spermatozoa/cytology; Spermatozoa/drug effects*; Spermatozoa/metabolism
LY294002, a PI3K pathway inhibitor, prevents leptin-induced adverse effects on spermatozoa in Sprague-Dawley rats

Md Mokhtar AH, Malik IA, Abd Aziz NAA, Almabhouh FA, Durairajanayagam D, Singh HJ

Andrologia, 2019 Apr;51(3):e13196.
PMID: 30456785 DOI: 10.1111/and.13196

This study examined the effects of PI3K and AMPK signalling pathway inhibitors on leptin-induced adverse effects on rat spermatozoa. Sprague-Dawley rats, aged 14-16 weeks, were randomised into control, leptin-, leptin + dorsomorphin (AMPK inhibitor)-, and leptin+LY294002 (PI3K inhibitor)-treated groups with six rats per group. Leptin was given once daily for 14 days via the intraperitoneal (i.p.) route at a dose of 60 ug kg-1 body weight. Rats in the leptin and inhibitor-treated groups received concurrently either dorsomorphin (5 mg kg-1 day-1 ) or LY294002 (1.2 mg kg-1 day-1 ) i.p. for 14 days. Controls received 0.1 ml of normal saline. Upon completion, sperm count, sperm morphology, seminiferous tubular epithelial height (STEH), seminiferous tubular diameter (STD), 8-hydroxy-2-deoxyguanosine (8-OHdG) and phospho-Akt/total Akt ratio were estimated. Data were analysed using ANOVA. Sperm count, STEH and STD were significantly lower, while the percentage of spermatozoa with abnormal morphology and the level of 8-OHdG were significantly higher in rats treated with leptin and leptin + dorsomorphin when compared to those in controls and LY294002-treated rats. Testicular phospho-Akt/total Akt ratio was significantly higher in leptin and leptin + LY294002-treated rats. In conclusion, LY294002 prevents leptin-induced changes in rat sperm parameters, suggesting the potential role of the PI3K signalling pathway in the adverse effects of leptin on sperm parameters.

Matched MeSH terms: Spermatozoa/drug effects*
Adverse effects of leptin on histone-to-protamine transition during spermatogenesis are prevented by melatonin in Sprague-Dawley rats

Almabhouh FA, Singh HJ

Andrologia, 2018 Feb;50(1).
PMID: 28497500 DOI: 10.1111/and.12814

This study examines the effect of melatonin on leptin-induced changes in transition of histone to protamine in adult rats during spermatogenesis. Twelve-week-old Sprague-Dawley rats were randomised into control, leptin-, leptin-melatonin-10-, leptin-melatonin-20- and melatonin-10-treated groups with six rats per group. Leptin was given via intraperitoneal injections (i.p.) daily for 42 days (60 μg/kg body weight). Rats in the leptin- and melatonin-treated groups were given either 10 or 20 mg day-1 kg-1 body weight of leptin in drinking water. Melatonin-10-treated group received only 10 mg of melatonin day-1 kg-1 body weight in drinking water for 42 days. Control rats received 0.1 ml of 0.9% saline. Upon completion of the treatment, sperm count, morphology and histone-to-protamine ratio were estimated. Gene expression of HAT, HDAC1, HDAC2, H2B, H2A, H1, PRM1, PRM2, TNP1 and TNP2 was determined. Data were analysed using ANOVA. Sperm count was significantly lower, whereas the fraction of spermatozoa with abnormal morphology, the ratio of histone-to-protamine transition and the expressions of HAT, HDAC1, HDAC2, H2B, H2A, H1, PRM1 were significantly higher in leptin-treated rats than those in controls or melatonin-treated rats. It appears that exogenous leptin administration adversely affects histone-to-protamine transition, which is prevented by concurrent administration of melatonin.

Matched MeSH terms: Spermatozoa/drug effects*; Spermatozoa/metabolism
The impact of leptin on sperm

Almabhouh FA, Singh HJ

Reprod Fertil Dev, 2023 May;35(8):459-468.
PMID: 37196661 DOI: 10.1071/RD22222

Despite its important role in numerous physiological functions, including regulation of appetite and body weight, immune function and normal sexual maturation, raised leptin levels could result in significant damaging effects on sperm. The adverse effects of leptin on the male reproductive system result from its direct actions on the reproductive organs and cells instead of the hypothalamus-pituitary-gonadal axis. Binding of leptin to the receptors in the seminiferous tubular cells of the testes increases free radical production and decreases the gene expression and activity of endogenous enzymatic antioxidants. These effects are mediated via the PI3K pathway. The resultant oxidative stress causes significant damage to the seminiferous tubular cells, germ cells and sperm DNA leading to apoptosis, increased sperm DNA fragmentation, decreased sperm count, increased fraction of sperm with abnormal morphology, and decreased seminiferous tubular height and diameter. This review summarises the evidence in the literature on the adverse effects of leptin on sperm, which could underlie the often-reported sperm abnormalities in obese hyperleptinaemic infertile males. Although leptin is necessary for normal reproductive function, its raised levels could be pathologic. There is, therefore, a need to identify the cut-off level in the serum and seminal fluid above which leptin becomes pathological for better management of leptin associated adverse effects on male reproductive function.

Matched MeSH terms: Spermatozoa/metabolism

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