DNA damage is frequently encountered in spermatozoa of subfertile males and is correlated with a range of adverse clinical outcomes including impaired fertilization, disrupted preimplantation embryonic development, increased rates of miscarriage and an enhanced risk of disease in the progeny. The etiology of DNA fragmentation in human spermatozoa is closely correlated with the appearance of oxidative base adducts and evidence of impaired spermiogenesis. We hypothesize that oxidative stress impedes spermiogenesis, resulting in the generation of spermatozoa with poorly remodelled chromatin. These defective cells have a tendency to default to an apoptotic pathway associated with motility loss, caspase activation, phosphatidylserine exteriorization and the activation of free radical generation by the mitochondria. The latter induces lipid peroxidation and oxidative DNA damage, which then leads to DNA fragmentation and cell death. The physical architecture of spermatozoa prevents any nucleases activated as a result of this apoptotic process from gaining access to the nuclear DNA and inducing its fragmentation. It is for this reason that a majority of the DNA damage encountered in human spermatozoa seems to be oxidative. Given the important role that oxidative stress seems to have in the etiology of DNA damage, there should be an important role for antioxidants in the treatment of this condition. If oxidative DNA damage in spermatozoa is providing a sensitive readout of systemic oxidative stress, the implications of these findings could stretch beyond our immediate goal of trying to minimize DNA damage in spermatozoa as a prelude to assisted conception therapy.

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Apoptosis and DNA damage in human spermatozoa.

Background Male infertility affects >20 million men worldwide and represents a major health concern. Although multifactorial, male infertility has a strong genetic basis which has so far not been extensively studied. Recent studies of consanguineous families and of small cohorts of phenotypically homogeneous patients have however allowed the identification of a number of autosomal recessive causes of teratozoospermia. Homozygous mutations of aurora kinase C (AURKC) were first described to be responsible for most cases of macrozoospermia. Other genes defects have later been identified in spermatogenesis associated 16 (SPATA16) and dpy-19-like 2 (DPY19L2) in patients with globozoospermia and more recently in dynein, axonemal, heavy chain 1 (DNAH1) in a heterogeneous group of patients presenting with flagellar abnormalities previously described as dysplasia of the fibrous sheath or short/stump tail syndromes, which we propose to call multiple morphological abnormalities of the flagella (MMAF). Methods A comprehensive review of the scientific literature available in PubMed/Medline was conducted for studies on human genetics, experimental models and physiopathology related to teratozoospermia in particular globozoospermia, large headed spermatozoa and flagellar abnormalities. The search included all articles with an English abstract available online before September 2014. Results Molecular studies of numerous unrelated patients with globozoospermia and large-headed spermatozoa confirmed that mutations in DPY19L2 and AURKC are mainly responsible for their respective pathological phenotype. In globozoospermia, the deletion of the totality of the DPY19L2 gene represents ∼ 81% of the pathological alleles but point mutations affecting the protein function have also been described. In macrozoospermia only two recurrent mutations were identified in AURKC, accounting for almost all the pathological alleles, raising the possibility of a putative positive selection of heterozygous individuals. The recent identification of DNAH1 mutations in a proportion of patients with MMAF is promising but emphasizes that this phenotype is genetically heterogeneous. Moreover, the identification of mutations in a dynein strengthens the emerging point of view that MMAF may be a phenotypic variation of the classical forms of primary ciliary dyskinesia. Based on data from human and animal models, the MMAF phenotype seems to be favored by defects directly or indirectly affecting the central pair of axonemal microtubules of the sperm flagella. Conclusions The studies described here provide valuable information regarding the genetic and molecular defects causing infertility, to improve our understanding of the physiopathology of teratozoospermia while giving a detailed characterization of specific features of spermatogenesis. Furthermore, these findings have a significant influence on the diagnostic strategy for teratozoospermic patients allowing the clinician to provide the patient with informed genetic counseling, to adopt the best course of treatment and to develop personalized medicine directly targeting the defective gene products.

Teratozoospermia: spotlight on the main genetic actors in the human

BACKGROUND: Mammalian oocytes are activated by intracellular calcium (Ca(2+)) oscillations following gamete fusion. Recent evidence implicates a sperm-specific phospholipase C zeta, PLCζ, which is introduced into the oocyte following membrane fusion, as the responsible factor. This review summarizes the current understanding of human oocyte activation failure and describes recent discoveries linking certain cases of male infertility with defects in PLCζ expression and activity. How these latest findings may influence future diagnosis and treatment options are also discussed. METHODS: Systematic literature searches were performed using PubMed, ISI-Web of Knowledge and The Cochrane Library. We also scrutinized material from the United Nations and World Health Organization databases (UNWHO) and the Human Fertilization and Embryology Authority (HFEA). RESULTS AND CONCLUSIONS: Although ICSI results in average fertilization rates of 70%, complete or virtually complete fertilization failure still occurs in 1-5% of ICSI cycles. While oocyte activation failure can, in some cases, be overcome by artificial oocyte activators such as calcium ionophores, a more physiological oocyte activation agent might release Ca(2+) within the oocyte in a more efficient and controlled manner. As PLCζ is now widely considered to be the physiological agent responsible for activating mammalian oocytes, it represents both a novel diagnostic biomarker of oocyte activation capability and a possible mode of treatment for certain types of male infertility.

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Oocyte activation, phospholipase C zeta and human infertility

Fertility in the male is dependent on the proper production of sperm cells. This pro- cess, called spermatogenesis is very complex and involves the synchronization of numerous factors. The presence of pro-inflammatory cytokines, tumor necrosis fac- tor-alpha (TNF-α), interleukin-1 alpha (IL-1 α) and interleukin 1 beta (IL-1 β) cy- tokines in the male reproductive tract (testis, epididymis and sperm) may have cer- tain physiological functions. However, when the levels of these cytokines are higher than normal, as seen in conditions of inflammation, they become very harmful to sperm production. Moreover, inflammation is also associated with oxidative stress and the latter is well known to impair sperm function. Epidemiological studies re- garding male infertility have revealed that more and more infertile men suffer from acute or chronic inflammation of the genitourinary tract, which often occurs without any symptoms. The inflammatory reactions within the male genital tract are inevita- bly connected with oxidative stress. Oxidative stress, especially in sperm, is harmful because it damages sperm DNA and causes apoptosis in sperm. This article reviewed the suggested mechanisms and contribution of inflammation to male infertility. In addition, the review was further strengthened by discussing how inflammation af- fects both fertility and assisted reproductive technologies (ART).

/pdf/impact-of-inflammation-on-male-reproductive-tract-366v1ogtol.pdf

Impact of Inflammation on Male Reproductive Tract.

https://www.fertstert.org/article/S0015-0282(13)03059-8/pdf

MicroRNA expression profiles in human testicular tissues of infertile men with different histopathologic patterns

Infertility is defined as a failure to conceive in a couple trying to reproduce for a period of two years without conception. Approximately 15 percent of couples are infertile, and among these couples, male factor infertility accounts for approximately 50 percent of causes. Male infertility is a multifactorial syndrome encompassing a wide variety of disorders. In more than half of infertile men, the cause of their infertility is unknown (idiopathic) and could be congenital or acquired. Infertility in men can be diagnosed initially by semen analysis. Seminograms of infertile men may reveal many abnormal conditions, which include azoospermia, oligozoospermia, t e r at ozoos p e r mi a , a s t he nozoos p e r mi a , necrospermia and pyospermia. The current estimate is that about 30 percent of men seeking help at the infertility clinic are found to have oligozoospermia or azoospermia of unknown aetiology. Therefore, there is a need to find the cause of infertility. The causes are known in less than half of these cases, out of which genetic or inherited disease and specific abnormalities in the Y chromosome are major factors. About 10–20 percent of males presenting without sperm in the ejaculate carry a deletion of the Y chromosome. This deleted region includes the Azoospermia Factor (AZF) locus, located in the Yq11, which is divided into four recurrently deleted non-overlapping subregions designated as AZFa, AZFb, AZFc and AZFd. Each of these regions may be associated with a particular testicular histology, and several candidate genes have been found within these regions. The Deleted in Azoospermia (DAZ) gene family is reported to be the most frequently deleted AZF candidate gene and is located in the AZFc region. Recently, a partial, novel Y chromosome 1.6-Mb deletion, designated “gr/gr” deletion, has been described specifically in infertile men with varying degrees of spermatogenic failure. The DAZ gene has an autosomal homologue, DAZL (DAZ-Like), on the short arm of the chromosome 3 (3p24) and it is possible that a defective autosomal DAZL may be responsible for the spermatogenic defect. The genetic complexity of the AZF locus on the long arm of the Y chromosome could be revealed only with the development of sequence tagged sites. Random attacks on the naked mitochondrial DNA (mtDNA) of sperm by reactive oxygen species or free radicals will inevitably cause oxidative damage or mutation to the mitochondrial genome with pathological consequences and lead to infertility in males. The key nuclear enzyme involved in the elongation and repair of mtDNA strands is DNA polymerase gamma, mapped to the long arm of chromosome 15 (15q25), and includes a CAG repeat region. Its mutation affects the adenosine triphosphate production. The introduction of molecular techniques has provided great insight into the genetics of infertility. Yet, our understanding of the genetic causes of male infertility remains limited.

/pdf/genetics-of-human-male-infertility-1158u7fbi5.pdf

Genetics of human male infertility

Solanum tuberosum commonly known as potato belongs to solanaceae family. The whole part of potato plant including leaves; tuber, peel and juice are used in traditional medicine. A number of pharmacological activities of potato have been reported viz. Antioxidant, anticancer, antiallergy, antibacterial, anti-inflammatory, antiobesity, anti-ulcer activity. Potato contains Phenolic acids, anthocyanin, flavonoids, vitamin B6, vitamin B3, pantothenic acid, potassium, manganese, phosphorous; copper and fibres. The medicinal properties, traditional uses, nutritional value, phytochemical constituents, taxonomy, geographic origin and distribution have been mentioned in this present review to provide collective data for multipurpose benefits.

https://www.arjournals.org/index.php/ijpm/article/download/2256/1140

Solanum tuberosum L: Botanical, Phytochemical, Pharmacological and Nutritional Significance

Biofertilizer for crop production and soil fertility.

Colocasia esculenta is a tropical plant grown primarily for its edible corms, the root and vegetables. It is most commonly known as taro and is widely cultivated in the high rainfall areas under flooded condition usually by small farmers. This study details about morphological characters of taro and their use as food and; region and season of cultivation.

https://www.plantsjournal.com/archives/2018/vol6issue4/PartC/6-4-19-887.pdf

Taro (Colocasia esculenta): An overview

Papaya seeds are reported to have higher therapeutic potential in comparison to the fruits in which they reside. Thus, the present in-vitro study aimed to evaluate and compare the anti-oxidant, anti-inflammatory and anti-microbial effect of seed extracts on Carica papaya L. (Caricaceae). The bioactive form the seeds were sequentially fractionated with hexane, chloroform, diethyl ether, and methanol in the increasing order of polarity. Total phenolic and flavonoid contents were estimated. These extracts were assessed for an antioxidant property by 1, 1-diphenyl-2-picryl-hydroxyl (DPPH) method and reducing power assay was carried out using the FeCl3 method. Inhibition of 15-lipoxygenase (LOX) by these extracts at 5 25μg to asses anti-inflammatory capacity was studied. Antibacterial activity against some human pathogenic bacteria was tested by agar disk diffusion method. Among all the organic solvent extracts, methanolic extracts exhibited good antioxidant and antibacterial activity. Methanolic extract with an IC50 value of 48mg for LOX inhibition is reported. The extracts showed inhibition of human pathogenic bacteria in the order: Escherichia coli >Pseudomonas vulgaris>Klebsiella pneumonia. Significant and positive linear correlations were found between total antioxidant capacities and phenolic contents indicating that phenolics were the dominant antioxidant constituents in tested seeds. Methanol extracts of C.papaya were subjected to LC-MS metabolite profiling. The LC-MS analysis identified 6 metabolites p-hydroxybenzoic acid, salicylic acid, hyperoxide, genteel alcohol, triallyl glucose, kaemferolhexoside as the main constituents for the first time from this seed extract. Our study demonstrated that the selected papaya seeds have good antioxidant, antiinflammatory, and antibacterial properties.

/pdf/in-vitro-antioxidant-anti-inflammatory-and-anti-microbial-1ryy8zlh64.pdf

Gopenath Ts

Papers

Genetics of human male infertility

Solanum tuberosum L: Botanical, Phytochemical, Pharmacological and Nutritional Significance

Biofertilizer for crop production and soil fertility.

Taro (Colocasia esculenta): An overview

In Vitro Antioxidant, Anti-Inflammatory And Anti-Microbial Activity of Carica Papaya Seeds