• <tr id="yyy80"></tr>
  • <sup id="yyy80"></sup>
  • <tfoot id="yyy80"><noscript id="yyy80"></noscript></tfoot>
  • 99热精品在线国产_美女午夜性视频免费_国产精品国产高清国产av_av欧美777_自拍偷自拍亚洲精品老妇_亚洲熟女精品中文字幕_www日本黄色视频网_国产精品野战在线观看 ?

    Excess iodine exposure: An emerging area of concern for male reproductive physiology in the post-salt iodization era

    2021-06-05 02:03:00ArijitChakraborty
    Asian Pacific Journal of Reproduction 2021年3期

    Arijit Chakraborty

    Department of Sports and Exercise Science, Somaiya Sports Academy, Somaiya Vidyavihar University, Vidyanagar, Vidya Vihar East, Vidyavihar, Mumbai,Maharashtra 400077, India

    ABSTRACT

    KEYWORDS: Iodine deficiency; Iodine excess; Reactive oxygen species; Thyroid; Testis; Lipid peroxidation level; Male infertility

    1. Introduction

    Iodine is an indispensable micro-nutrient required for animals as structural and functional element for biosynthesis of thyroid hormones. By virtue of thyroid hormones, iodine exerts a significant role in basal metabolic rate and on the overall expression of genes that impart many physiological functions, including embryogenesis and growth, reproduction along with advancement of neurological and cognitive functions. Iodine apart from its pivotal role for the synthesis of thyroid hormone, contributes in a number of clinically important collaborations with the functioning of thyroid gland[1].The principal role of the thyroid gland is secretion and release of the hormones thyroxine (T), triiodothyronine (T) and calcitonin.Nearly 80% of the Tis converted to Tby peripheral organs such as the liver, kidney and spleen by deiodinases, which are selenium containing enzymes[2]. Tis about ten times biologically more active than T[3]. The total deficiency of thyroid hormones can reduce basal metabolic rate up to 50%, while in excessive production, the same can be increased by as large as 100%[4]. Tacts largely as a precursor to T, which is (with minor exceptions) the natural active hormone. Biologically active thyroid hormones have also been well known for its critical regulation of pre- and post-implantation embryo development[5].

    Humans need optimum iodine for their appropriate physical,reproductive and mental development among others[6]. In an adult with sufficient iodine intake, approximately 15-20 mg iodine is concentrated in the tissues of the thyroid gland[3]. However, it has been postulated that only 30 percent of the body’s iodine is concentrated in the thyroid tissue and thyroid hormones while the remaining non-hormonal iodine is found in a variety of tissues,including mammary gland, eye, gastric mucosa, cervix, prostate,reproductive organs (testis and ovary) and salivary glands[4]. With the exception of mammary tissue, the function of iodine in these extra-thyroidal tissues is largely unknown[7]. However, it has been hypothesized that the relationship between iodine intake and the risk of thyroid disease is ‘U’-shaped, with both low and high iodine intakes associated with altered thyroid function[8]. Indiscriminate intake of iodine resulting in hypo- and hyper-thyroidism is detrimental to thyroid function; the latter is emerging as a global concern in the present environmental scenario[9]. Altered thyroid status is known to adversely affect many organs and tissues including male and female reproduction[10]. Clinical data correlating the effects of excessive iodine supplementation on reproduction mainly male reproductive physiology is partial, probably because thyroid diseases are more common in females than in males[11]. It has also been indicated that pregnant women in excess iodine environment experience some kind of child birth related dysfunction[12]. The thyroid gland has auto- regulatory mechanism by which it can limit the entry of excess iodine through Wolff-Chaikoff effect but up-to a certain level[13]; however, no such phenomenon has not been studied on testicular tissues[14].

    The existence of thyroid hormone receptors on germ cells suggests a probable role of thyroid hormones in sustaining differential population of cells in testicular milleu[15]. Thyroid hormone receptors are identified on different stages of developing rat germ cells viz. gonocyte, spermatogonia, preleptotene, leptotene,pachytene, zygotene, round and elongating spermatids[16]. Thyroid hormone receptor (TR)α and TRβ1 are mutually expressed during different stages of germ cell development as TRβ1 first appears in intermediate type spermatogonia while TRα first appears in type B spermatogonia[17]. There have been recent reports of male reproductive deterioration in type A and B spermatogonia’s following excess iodine exposure having euthyroid condition[14];also significant presence of iodine transport channels in germinal and Leydig cells[18] favour testis for a potent iodine concentrating organ.These results strongly indicate towards optimum level of iodine as an independent regulator of male reproductive functions; however, the correlation is yet to be reconnoitred in detail. Effect of excess iodide on male reproduction especially on testicular and spermatozoal morphology with functional status even in experimental models needs to be explored further to delineate its possible role in the persistence of human infertility. This review concerns those aspects of research involving excess iodine with special reference to male reproductive endocrinology. Elemental iodine is a halogen with an atomic mass of 126.9 Da which exists in the oxidation states 1 (Ianion or iodide) to +7 (IO? anion or periodate) in the environment.Iodides and iodates (IOanion, oxidation state +5) occur ubiquitously in igneous rocks and soils, liberated by weathering and erosion, leached by rainwater into surface water and the seas.In many areas of the world, the surface soil becomes progressively poorer in iodine through these leaching processes[19]. Liberated elemental iodine evaporates into the atmosphere and is precipitated by rainfall into the land surface completing the environmental iodine cycle. The iodides in the sea accumulate in marine organisms,whereas, on land, small amounts of iodine are taken up by plants that are subsequently ingested by herbivores[20].

    The availability of iodine is found in a wide variety of foodstuffs the richest sources being dairy products and fish. Seaweed is an intense source of iodine, but it can provide excessive amounts (particularly so in the case of brown seaweed such as kelp), and therefore consumption of seaweed more than once a week is generally not recommended, especially during pregnancy and lactation[21,22]. Milk and dairy products are the main sources of iodine for most people,irrespective of demographic and geographical variations in addition to consumption of iodized salt. Research has shown that organic milk has a 40% lower iodine content than conventional milk[4].For implementation of universal salt iodization policy in most of the countries, iodine is added to table salt to give “iodised salt” for possible prevention from iodine deficiency disorders. Packaged iodised salt is exclusively distributed in the different countries and very popular in general supermarket chains and consumed by all strata of populations irrespective of their socio-economic status. It is further reasonable to consider that the actual amount of iodine in food varies according to the iodine content of the soil, farming practice, fish species and seasonal variations[23]. Iodine is present in nature in various forms such as inorganic sodium and potassium salts(iodides and iodates), inorganic diatomic iodine (molecular iodine or I) and organic monoatomic iodine. Iodides (I) are absorbed via transport protein in the gastric mucosa called the sodium-iodide symporter, found in a variety of tissues in the body that utilize and concentrate iodine such as the thyroid, mammary tissue, salivary gland, cervix including the reproductive organs[24]. However, certain generic medicines, elemental agents for water purification, topical antiseptics and iodinated radiologic contrast agents are appreciable sources of exposure to iodine in excess[25] and might be impulsive in developing hypo-/ hyper-thyroidism in selected individuals.

    2. Sources of iodine excess

    2.1. Iodine supplementation

    Considering its importance, iodine is put into table salt to make sure that everyone has enough iodine in their bodies to form essential thyroid hormones as a part of Universal Salt Iodization Programme. Iodine has also been administrated as iodized oil orally and intramuscularly, introduced into the water supply, used in crop irrigation, incorporated into animal fodder and introduced into food,bread iodophores and other dietary products. Fortified micronutrient biscuits have also been successfully used to raise the median urinary iodine concentrations of schoolgirls (aged 10-15 years) in India[26].

    2.2. Iodinated supplements

    Several cases of congenital hypothyroidism caused by ingestion of excess maternal iodine tablets during pregnancy and lactation have been reported[27]. Similarly, hypothyroidism in new-borns to mothers who ingested excessive amounts of seaweed or seaweed soup during both pregnancy[28] and lactation have been reported[29] indicating risks of potential iodine-induced thyroid dysfunction .

    2.3. Medications

    Amiodarone, an iodine-rich medication used in the management of ventricular and supraventricular tachyarrhythmia, is probably the most important and common source of medication-induced thyroid dysfunction. Amiodarone is 37% iodine by weight and has some structural resemblance to the thyroid hormones Tand T[30].Thus, one 200 mg tablet of amiodarone contains 75 mg iodine,which is several hundred-fold higher than the recommended daily intake of 150 μg in adults that may result in excess iodine intake when consumed regularly[31]. Our group has demonstrated the risk of amiodarone induced toxic changes in all the thyroid hormone responsive organs mainly because of its high iodine content[30].Providine-iodine solutions commonly used to treat local infections is also another source for excess iodine intake especially in populations residing in environmentally iodine sufficient regions[20].

    2.4. Diet

    Diet is considered as one of the most effective forms of iodine nutrition. The iodine content of foods is highly variable between food categories as well as within each category. The richest sources are marine products (such as fish, shellfish, molluscs and seaweed),eggs and milk, as well as their derivatives. Iodine content of milk and eggs is also influenced by feeding and hygienic practices[19,32].

    2.5. Radiologic contrast media

    Use of iodinated contrast agents in diagnostic radiologic studies is a common source of excess iodine exposure in many patients.Following exposure to an iodinated contrast agent, iodine stores in the body remain elevated and provide a continuous pool that can potentially induce thyroid dysfunction which is ultimately deleterious to human body[33].

    2.6. Other sources of iodine supplementation

    Iodine exposure may be due to topical iodine supplementation which is frequently done in child care hospitals especially to neonates[34]. Other sources of potential excess iodine exposure include various expectorants, food preservatives and additives,prescribed medications, parenteral nutrition preparations,mouthwashes[35] and vaginal douches[36]. Some other natural sources of excess iodine exposure includes volatilization of iodine from the oceans, weathering of rock, and eruptions of volcanoes[37]also human activities like nuclear weapon testing, combustion of fossil fuel, poor waste management from municipal plants, undue combustion of iodinated waste and fossil fuels also highly aggravate the situation.

    2.7. Female reproduction and developmental effects

    Excess iodine has been shown to regulate serum progesterone profiles by altering the expression of androgen synthesizing enzymes as well as by down regulating progesterone responsive genes thereby leading to disrupted female reproductive system[38].Severe structural and functional alterations in ovarian morphology and uterine wall as evidenced by decreased luminal fluid secretion and glandular morphology was observed, that resulted from critical cellular and molecular modification in steroidogenic signalling pathway[39]. Our group has experimentally demonstrated that iodine when administered 100 times excess causes hypo-estrogenic effect in female reproductive system leading to anovulatory conditions and compromised fertility maintaining euthyroid condition however iodine at 500 times excess develops hyper-estrogenic situation giving rise to altered fertility status[39]. Thus, it exhibits biphasic mode of action depending on dose and durations raising serious concerns of female reproductive health in populations consuming iodine for considerably long periods. Thyroid hormone abnormality from any cause at initial phases of development may result in severe mental retardation, neurologic abnormalities, stunted growth, and/or abnormal pubertal development[40]. Embryotoxicity and teratogenicity have been reported because of reduced body weight in fetuses along with decreased number of live births and increased incidence of resorptions especially skeletal variations in pregnancy of those women who lived in iodine excess areas or were supplemented with high amounts of iodine during gestational period.These findings strongly indicate that exposure to maternally toxic doses of iodine may have a potential developmental toxic effect in the new-borns/neonates[41].

    It has been already established that oral exposure to excess stable iodine may produce hypo- or hyper-thyroidism and may cause disruption of reproductive system secondary to thyroid gland dysfunction[42]. Hypothyroidism can produce changes in the menstrual cycle in humans, including menorrhagia (excessive uterine bleeding) and anovulation (no ovulation) with incidences of abortions, stillbirths, and premature parturition[39,43]. Reproductive impairments associated with hyperthyroidism include amenorrhea,alterations in gonadotropin release and sex hormone-binding globulin, and changes in the levels and metabolism of steroid hormones in both sexes[43].

    3. Excess iodine and male reproduction

    3.1. Carrier mediated iodine transport in testicular cells

    Sodium-iodide symporter and pendrin are primarily involved in iodide (I) transport and entry into cells and tissues that accumulate iodine[44]. The sodium-iodide symporter is a basolateral plasma membrane transporter that facilitates active uptake of iodide into thyroidal follicular cells, the classical iodide concentrating endocrine organ[45]. Since iodide can be transported and accumulated not only in thyroid but also in many other tissues, it is predictable that presence of sodium-iodide symporter or its mRNA expression in extra-thyroidal tissues is categorically possible. Limited data are available on the sodium/iodide symporter expression in human testis,a potent thyroid hormone sensitive organ; however, recent reports have confirmed its localization and expression in both foetal and adult normal testis at various stages of development[46]. Sodiumiodide symporter is also found to be expressed in the large majority of seminomas and embryonal carcinomas of human testis, and its presence in the plasma membrane compartment of the tumor cells suggests that it may serve as potential carrier of radioiodine for an ablative treatment of cancer tissue[46]. Sodium-iodide symporter is a key plasma trans-membrane glycoprotein that catalyses the active accumulation of iodide (I) in the tissues concerned with iodide uptake; co-transports two sodium (Na) ions along with one iodide(I) ion, with the inter-membrane sodium gradient serving as the driving force for iodide uptake[47]. The sodium gradient is achieved by sodium-potassium ATPase (Na-K-ATPase) that regulates cellular Naand Klevels by active transport of Naoutside the cell against the gradient, and the energy for this transfer is generated through hydrolysis of ATP[48]. However, hyperactivity of thyroid gland requires an elevated uptake of iodide, which in turn depends on the Naelectrochemical gradient, and dissipation of that gradient by aggressive iodide transport would be minimized if there is an accompanying increase in the Na-K-pump[49]. Na-K-ATPase has been found to be located in the conventional basolateral position in rat testicular cells and epididymis; furthermore, its presence on apical membrane of Sertoli cells has also been identified[50].Experimental studies on mice revealed that iodine overload can cause a significant reduction in the activities of this crucial cation co-transporter when treated for longer duration, which suggested an overall detrimental effect not-only limiting to thyroid gland[51].Similar observations have also been reported when iodine in excess induced hypothyroidism has been suggestive of decreased Na-K-ATPase in different areas of brain, leading to decreased functional status with cognitive deficits[52]. It has been well documented that further sodium-iodide symporter-mediated iodide transport is parallelly inhibited by the Na-K-ATPase inhibitor ouabain as well as by the competitive inhibitors thiocyanate and perchlorate[53]suggesting a functional interrelationship and co-localization of those two transporters. However, molecular characterisation of sodiumiodide symporter to understand its fundamental mechanisms in post-translational regulation of proteins and its role in testicular cells under excess iodine environment is a crucial area for research,following which novel therapeutic interventions and strategies for this micronutrient ingestion may be established.

    Pendrin, an iodide/chloride transporter, which is expressed in the apical membrane of thyroid follicles, likely participate in the efflux of iodide into the follicular lumen[54]. Higher expression level of pendrin was found in the kidney, lungs, and reproductive tissues (including testes, ovaries, and uterus) than in the thyroid[55].It has been confirmed from the studies of Lacroix et al[56]that testis contains sodium-iodide symporter and pendrin by immunohistochemistry, whereas Sertoli cells were found to have positive immunostain for the latter. Higher expression of pendrin transcripts and its products (SLC26A4 protein) has been shown to be found in testis[57], suggesting its pivotal role in regulation of iodide metabolism, transport and its relation with male steroidogenesis.It has also been reported that the consumption of high-iodine diets elevates blood-iodine concentration[58]. Maroufan[59] and May &Vardaman[60] confirmed that a significant increase in serum iodine concentration of male and female broilers was recorded when various iodide concentrations ranging between 0.3 and 5 000.0 mg/kg were used. Cao et al[61] reported when laying hens were fed with diets containing 50 and 100 mg I/kg for 56 days,plasma iodine rise by factors of 1.35 and 2.01 respectively. Iodine containing diets in amounts of 3.5 and 11.0 mg I/kg for 74 days to laying hens resulted in occurrence of serum iodide peaks of 4.9 and 6.5 mg/L[62]. Our study also revealed that ingestion of extra iodine may concomitantly result in elevation of plasma iodine levels besides augmented testicular accumulation[16]. In addition to plasma iodine levels, urinary iodine concentrations are a convenient but imperfectly validated marker of iodine intake. Initially, 24-hour urinary iodine excretion pattern was assumed to correspond to dietary intake of iodine; however, this is uncertain because urinary iodine content more closely relates to systemic adaptation to iodine supply, rather than being a reliable marker of the risks of iodine inadequacy. However, urinary iodine excretion may be a useful marker of adequacy or excess but its value at marginally adequate or inadequate intakes is uncertain[63]. In an recently concluded investigation on adult male animal models, it has been reported that administration of iodine in excess results in higher urinary and tissue concentrations of iodine in relation to the control[14]. Higher concentration of semen-iodine has also been associated to excess iodine intake and consequent development of infertility[64] - all these findings strongly indicating towards elemental iodine to have a promising effect on male fertility independent of thyroid hormone actions; the interrelationship of which needs to be further explored in details.

    3.2. Excess iodine and male reproductive performance

    3.2.1. Tissue morphology and function

    Iodine in excess has been shown to alter gross morphology of the testis[65]. Overall testicular germ cell degeneration has also been reflected by a marked reduction in all the consecutive stages of germ cells indicating impairment of spermatogenic process in experimental models[14]. Comparable results were also obtained following treatment with amiodarone, an excess iodine-containing drug, on testicular morphology, structure and function with the developed cytotoxicity ameliorated by antioxidant rich grape fruit extract[66]. Ultrastructure analysis by electron microscopy further revels testicular deterioration with relatively compressed seminiferous tubules lined with irregular outlines of the basement membrane accompanied with tubular shrinkage and altered surface architecture induced by iodine in excess[67]. Iodine at 500 times of its normal recommended dietary allowance level has also been reported to affect accessory male sex organs namely epididymis, prostrate,seminal vesicles and coagulating gland in animal models by altering their secretory functions[67] (Figure 1). The basic function of the epididymis is to store the immature sperms for their final maturation in male genetalia, and histologically it consists of lumens containing numerous sperms surrounded by columnar epithelial cells that secrete viscous fluid which provides nutrition to the sperms for their final maturation[68]. Excess iodine exposure results in shrinkage in diameter of lumens of the cauda epididymis accompanied with cellular damage and presence of very few sperms compared to the control, possible reason being the generation of cellular oxidative stress as a result of iodine in excess exposure[16]. The Itransport system in prostate gland involves the expression of the specific sodium iodide symporter and in some cases also pendrin[69] that makes it a potent iodide concentrating organ in addition to thyroid gland. Prostate gland normally is surrounded with the luminal ducts lined by tall columnar secretary epithelial cells and the lumens were filled with prostatic fluid and in excess iodine treatment, prostatic lumens were constricted, the surrounding epithelium layer were flat,with substantial absence of prostatic fluid in the lumen resembled vacuole like appearance[14]. Studies on in vitro culture show that molecular iodine, or diiodine (I), induces cell arrest and apoptosis in cancerous cell lines of prostate[70]. In general, seminal vesicles engulf the liquid that mixes with sperm to form semen. Secretion of seminal fluid is important for semen coagulation, sperm motility, and stability of sperm chromatin and suppression of the immune activity in the female reproductive tract[71] (Figure 1). Excess iodine exposure has been shown to cause a marked reduction in the luminal space as well as reduction in the surrounding epithelial layer which may be possibly for the cellular reactive oxygen species (ROS)-induced tissue injury[16]. Coagulating glands located behind the urinary bladder of normal animals showed markeded folded epithelial invaginations surrounding the lumen. These glands produce a fluid that contains fructose which provides an energy source for the sperm,as well as contributes to the mobility and viability of the sperm[72].Coagulating gland of excess iodide-exposed animals has been shown to be constricted with irregularly shaped lumen surrounded by less secretory flat epithelial cells demarcating deteriorated structure with altered functional characteristics[14]. Gasparich et al[73] showed a histopathological examination of epididymal tissues in patients on amiodarone therapy, and further reported fibrosis and lymphocytic infiltration in the seminiferous tubules leading to disturbance of spermatogenesis leading to male infertility.

    Figure 1. Schematic diagram shows the mechanistic effects of excess iodine consumption in the overall aspects of male reproductive physiology.

    3.2.2. Excess iodine and spermatogenesis

    Optimal thyroid function by adequate iodine intake is necessary for maintenance of spermatogenesis as the testis contains thyroid hormone receptors type 1 (TR-1)[74]. However, indiscriminate intake of iodine even in euthyroid condition can also lead to defective testicular functions and hence spermatogenesis[14]. Presence of sodium-iodide symporter on testicular cells makes iodine an important regulatory element for the control and progression of spermatogenesis, the function of which is largely unknown.Steroidogenic enzymes responsible for the biosynthesis of various steroid hormones including progestin, androgen and estrogen from cholesterol are several specific cytochrome P450 enzymes,hydroxysteroid dehydrogenases (HSDs) and steroid reductases[75]which are largely affected by excess iodine administration.The HSDs, which include the 3β-HSD and the 17β-HSD, are involved in the reduction and oxidation of steroid hormones requiring NAD/NADPas acceptors and their reduced forms as donors of reducing equivalents and are considered as rate limiting enzymes for testosterone biosynthetic pathway which were altered significantly when exposed to iodine in excess[67,76]. Excess iodine has been shown to be imposing hypothyroidism in both humans and experimental animals[77,78], that reflects in a decreased plasma testosterone level and the testosterone binding globulin in plasma[79].Chakraborty et al[14] reported that both acute and chronic exposure to excess iodine caused down-regulation of testicular Δ3β-HSD and 17β-HSD that are considered as key enzymes of testosterone biosynthesis and suppression of testosterone level under its influence might be the possible reason for interruption of growth and differentiation of the germ cell leading to their consequal degeneration. In addition, gonadotrophins viz. luteinizing and follicle-stimulating hormones are necessary for quantitative normal spermatogenesis and are the pivotal endocrine factors controlling testicular functions[80]. Both the levels of luteinizing and folliclestimulating hormone were significantly altered when iodine in excess was supplemented in experimental animals in sub-chronic durations due to interruption of hyothalamo-pituitary-gonadal axis[16] justifying the observable changes. Shoyinka et al[65] found that high dietary iodine leads to depressed spermatogenesis and reduces the survival period of the spermatocytes in the epididymis of iodine-supplemented rats with higher testicular organosomatic index.On the contrary, iodine supplementation at optimal doses restored fertility of sheep living in iodine deficient areas and may represent a means to achieve a silent iodine prophylaxis of local populations[81].Lewis[82] reported that feeding of 5 000 mg I/kg diet to domestic foul resulted in delayed spermatogenesis of about 10 days when compared to control counterparts. It has been postulated that excess iodine, might act directly on gonadal cells, resulting in a inhibition of spermatogenesis and hence fertility[83]. It has been confirmed that chronic daily oral administration of iodine, in the form of tincture mixed with the food, produced regression of the seminal vesicles and testicular damage restricted to the Leydig cells[84]. There are also reports of clinical cases where transient impaired testicular function was observed following exposures toI for ablative treatment of thyroid cancer in men that included low sperm counts, azoospermia(absence of spermatozoa), and elevated serum concentrations of follicle stimulating hormone, which persisted for more than 2 years,but were usually of much shorter duration[85]. Amiodarone, an excess iodine-containing drug, has been found to have dose-dependent degenerative and apoptotic effects on rat testes with a relatively higher number of cells positive for Terminal deoxynucleotidyl transferase dUTP nick end labelling, caspase-3, caspase-9 and Bax,suggesting a dose-dependent increase in the apoptosis under the effect of this iodinated medication[86]. Chronic ingestion of this excess iodine-containing drug has resulted in testicular dysfunction and infertility in patients along with atrophic testis and hyperresponsiveness to gonadotropin-releasing hormone[87]. The results of those studies indicate that iodine present in amiodarone may be significant factor responsible for those alterations, and the intricate details need to be explored. Blood testis barriers which are composed of cytoskeletal components are of extremely important in maintaining and progression of spermatogenesis. Excess iodine results in generation of free oxygen derived radicals that decrease the expression of adherens junctional proteins including proteins involved in Sertoli-Sertoli tight junctions or Sertoli-germ cell junctions along with downregulation of focal adhesion kinase[16]which is considered as a master regulator for blood testis barrier dynamics causing disruption of blood testis barrier and hence reduced overall spermatogenesis.

    Elevation of adreno-cortical pathway has also been considered as a potential inhibitor of spermatogenesis; the fundamental details have been worked out by Chakraborty et al[14]. Iodine in this study has been found to be associated with adrenal stress signalling mechanisms which resulted in excess production of corticosterone,a factor associated to be involved in compromised spermatogenesis.Abd-Aziz et al[88] reconfirmed that corticosterone-induced oxidative stress and an inhibitory effect exerted at the hypothalamic-pituitarygonadal axis were evidenced by increased lipid peroxidation,reduced enzymatic antioxidant activities, and decreased testosterone production, which subsequently resulted in decreased fertilising capacity of epididymal sperm leading to poor pregnancy outcomes.Developmental toxicity and teratogenicity with skeletal variations after exposure of excess iodine was also noted in a study by Yang et al[89]; however, in a different study on sexual activity and semen characteristics on Friesian bulls, supplementation of iodine within normal ranges has a beneficial effect on semen quality and quantity,initial fructose concentration and improvement in endocrinological output of hormones along with a positive relationship with growth and maturation[90]. This confirms the biphasic action of iodine on metabolism and developmental endocrinology i.e. when consumed in recommended levels, it may be beneficial to reproductive health;however, excess consumption may lead to spermatogenic arrest hence failure in the reproductive process.

    Recently, it has been proposed that alterations in sperm functional status after excess iodine exposure caused a significant increase in spermatozoal DNA fragmentation and augmented the number of apoptotic sperms; however, the plasma membrane intactness/viability was decreased with deteriorated acrosome integrity as found in one of our study[67]. It is worthwhile to note that sperm DNA fragmentation has recently emerged as a valuable tool in defining male infertility and in assessing sperm functional characteristics.Sperm chromatin integrity tests in human reproductive system and its causative relationship with oxidative stress have been increasingly disclosed[91]. One of the striking features of sperm DNA fragmentation has been its high correlation with the risk of pregnancy loss[91]. The salient observations from Chandra and Chakraborty[67] also established the depolarisation of mitochondrial membrane potential and elevation of sub-haploid cells under exposure of iodine in excess of about 500 times more than the recommended level. All these observations strongly suggest iodine to be a potential male anti-fertility agent when administered in excess for longer durations. Abnormal and reduced sperm counts with coiled tail, aberrant sperm head and disintegrated morphological features were already established by our group under varying doses of iodine excess when administered to experimental animals[14].Increased intake in amount of iodine intake has been recommended as a probable cause of decline in sperm counts coinciding with the implementation of universal salt iodization in the United States,France and United Kingdom[92]. It would be wise to quantify the presence, number, and activity of iodine transporters in germ, Leydig and Sertoli cells for better assessment of function and its possible role in regulating steroidogenesis.

    3.2.3. Excess iodine and testicular oxidative stress

    Iodine is one of the most electron-rich atoms in the diet of marine and terrestrial organisms with iodide (I), acting as an ancestral electron-donor through peroxidase enzymes[7]. Iodine in excess may promote oxygen free radicals to reduce the antioxidant defence capability[13]. Iodine itself is a highly active molecule which can react with proteins, lipids, and nucleic acids to generate a variety of acyclic iodo-compounds accompanied by ROS generation and lipid peroxidation in the process, resulting in the damage to the structure of the cell membrane and mitochondrial membrane[93] (Figure 1).However, when ROS are over-produced, they become toxic and bring damage to cellular components, macromolecules including lipids, proteins and nucleic acids hence causing damage to DNA and RNA. A toxic effect of iodide given to iodine-deficient laboratory animals was already noted experimentally by various research studies[94]. Similar studies have shown that 4-hydroxynonenal,a toxic product resulting from lipid peroxidation, is increased in goitrous and in iodine-induced involution glands, which indicate that oxidative stress is greatly enhanced in these conditions[95].Testicular cells and spermatozoa are reported to have high amounts of polyunsaturated fatty acids[96]. During steroidogenesis, certain amount of ROS are generated due to leakage of electron outside the electron transfer chain that are normally counteracted by antioxidant enzyme defence system present in testis[16]. Any imbalance may thrust these radicals not only to stimulate lipid peroxidation but also produce an alteration in the level of protein and DNA causing cellular damage[13]. Excess iodine has been shown to elevate oxidative stress mediated by generation of ROS in thyroid as well as thyroid hormone sensitive organs. It has been postulated that iodide excess has pro-oxidant effects, leading to an increased lipid peroxides level and catalase activity in target tissues and blood that leads to a decreased Hdonor ability of the sera[13]. Similar observations have also been reported with elevation of testicular lipid peroxidation levels positively correlating with upregulation in primary testicular antioxidant defence system for acute phase of the study however subsequent downregulation in those parameters were observed when excess iodine was administered for longer periods suggesting it to be a potential oxidant causing cellular oxidative stress by altering the pro-/anti-oxidant balance[13]. Testicular architecture of fertile animals are abundant in poly unsaturated fatty acids (PUFA) that serve as precursor’s molecules in cell membrane glycerophospholipids and thereby serves as a protection of testicular cells against shift in fatty acid composition induced by dietary changes[97]. Ingestion of iodine in excess causes generation of iodinium (I) and hypoiodite (IO) ions as intermediate products which are extremely reactive and can cause lipid peroxidation not only in thyroid but also in extra thyroidal cells like testes[54,98].Molecular iodine is activated into a free radical intermediate by superoxide to iodide (I) that forms the basis of iodination[99] and under the influence of excess iodine free radical productions are elevated for more iodination resulting in oxidative stress and hence cellular damage. It has also been reported that organs containing elevated amounts of PUFAs like testis are more vulnerable to oxidative damage[100] in addition to the fact that two high energy consuming physiological processes namely spermatogenesis and steroidogenesis yield ROS as a biproduct[101] that are particularly counteracted by the anti-oxidant defence systems present in testis;however, any imbalance can lead to free radicals-induced cellular damage causing oxidative stress[15]. Superoxide dismutase, catalase and glutathione peroxidase all have been shown to be affected by ingestion of iodine excess. Elemental iodine has been considered as an important regulator for redox balance[102] and in excess amounts acts as pro-oxidant exerting oxidative damage. Similar findings have also been reported on spermatozoal structure and function as well where ROS were also generated as a result of excess iodine exposure in animal model[67] (Figure 1). PUFA has also been suggested to be found on sperms in addition to testis[103] and thus they are also vulnerable for oxidative damage. ROS-induced damage in sperms can also lead to their deformed structure and may be a causative factor for male infertility[104]. Generated ROS for excess iodine ingestion causes damaged acrosomal integrity, loss of mitochondrial membrane potential, reduced and motility, chromosomal aberrations,decrease in haploidy and apoptosis which all indicate towards male infertility and sterility. Recently, in a study involving infertile couples, it has been correlated that men with higher iodine levels had more morphological alteration in spermatozoa and exhibited lower motile sperm count respectively[64], indicating iodine may play a role in the quality of semen and its close association in determining the attributes of male infertility.

    4. Conclusions

    Role of elemental iodine has been primarily focused and attributed as an indispensable component of thyroid hormones; with its indiscriminate intake resulting in deficiencies or excess, more or less are corroborated with altered thyroidal structural and functional status. Recently, the presence of iodine transporters like sodiumiodide symporter in germ and Leydig cells; pendrin in Sertoli cells,strongly suggests a regulatory role of this trace element in male reproductive endocrinology. Therefore, considering the inadequacy of available substantial research outputs in this area, it is of high time to recognise the functions of iodine independent of thyroidal actions. Moreover, the association between iodized salt consumption,urinary iodine levels, ROS generation in testis and spermatozoa,decreased sperm number and motility with increased concentration of iodine in seminal plasma needs to be established as a causeeffect relationship to understand the role of iodine in excess on male infertility. This review provides novel insights and may serve as future strategies for establishing the independent role of iodine on male reproductive physiology, an emerging concern, which warrants further investigations.

    Conflict of interest statement

    The author declare no conflicts of interest.

    Author’s contributions

    Arijit Chakraborty planned, prepared the draft of the manuscript,and supervised the entire study.

    老鸭窝网址在线观看| 国产精品女同一区二区软件 | 亚洲色图av天堂| 午夜福利高清视频| 97超视频在线观看视频| 母亲3免费完整高清在线观看| 在线观看日韩欧美| 免费人成在线观看视频色| 免费av不卡在线播放| 男女午夜视频在线观看| 嫩草影院精品99| 精品熟女少妇八av免费久了| 18+在线观看网站| 在线天堂最新版资源| 亚洲美女视频黄频| 日韩欧美精品免费久久 | 日韩精品中文字幕看吧| www日本黄色视频网| 久久精品影院6| 深爱激情五月婷婷| 欧美黑人巨大hd| tocl精华| 亚洲精品影视一区二区三区av| 淫秽高清视频在线观看| 国产一区二区激情短视频| 久久久精品欧美日韩精品| 性色av乱码一区二区三区2| 成人午夜高清在线视频| 午夜福利在线观看吧| 毛片女人毛片| 青草久久国产| 国产麻豆成人av免费视频| 国产成人欧美在线观看| 尤物成人国产欧美一区二区三区| 中文字幕久久专区| 久久精品国产亚洲av涩爱 | 日本成人三级电影网站| 久久中文看片网| 免费搜索国产男女视频| 在线观看日韩欧美| 97超级碰碰碰精品色视频在线观看| 久久精品国产99精品国产亚洲性色| 国产v大片淫在线免费观看| 亚洲第一电影网av| 亚洲欧美日韩高清在线视频| 中文资源天堂在线| 国产精品98久久久久久宅男小说| 国产爱豆传媒在线观看| 在线观看一区二区三区| 19禁男女啪啪无遮挡网站| 最近最新免费中文字幕在线| 操出白浆在线播放| 亚洲一区高清亚洲精品| 国产综合懂色| 老司机深夜福利视频在线观看| 久久久久久人人人人人| 在线免费观看的www视频| 亚洲精华国产精华精| 亚洲欧美精品综合久久99| 免费av观看视频| 真人做人爱边吃奶动态| 亚洲成人免费电影在线观看| www.色视频.com| 日本a在线网址| 成人av在线播放网站| xxxwww97欧美| 亚洲男人的天堂狠狠| 亚洲av成人精品一区久久| 波多野结衣巨乳人妻| 久久久久国产精品人妻aⅴ院| 亚洲专区国产一区二区| 亚洲成人免费电影在线观看| 国产男靠女视频免费网站| 搡老岳熟女国产| 欧美午夜高清在线| 国产精品久久久久久精品电影| 国产91精品成人一区二区三区| 有码 亚洲区| 久久6这里有精品| 麻豆成人午夜福利视频| 欧美日韩亚洲国产一区二区在线观看| 国产成人av激情在线播放| 国产亚洲精品一区二区www| 欧美日韩精品网址| 精品电影一区二区在线| 国产真人三级小视频在线观看| 亚洲,欧美精品.| 亚洲欧美一区二区三区黑人| tocl精华| 在线播放国产精品三级| 在线播放无遮挡| 免费看a级黄色片| 观看美女的网站| 91麻豆av在线| 成年女人看的毛片在线观看| 噜噜噜噜噜久久久久久91| 成年免费大片在线观看| 婷婷精品国产亚洲av| 免费电影在线观看免费观看| 欧美日韩福利视频一区二区| 国产精品乱码一区二三区的特点| 久久久久久久久大av| 国产亚洲精品久久久com| 精品一区二区三区av网在线观看| av在线蜜桃| 国产精品三级大全| 老司机午夜福利在线观看视频| 757午夜福利合集在线观看| 最新中文字幕久久久久| 亚洲av免费高清在线观看| 精品国内亚洲2022精品成人| 91av网一区二区| 久久99热这里只有精品18| 国产免费av片在线观看野外av| 久久久久久大精品| 亚洲精品久久国产高清桃花| 狂野欧美激情性xxxx| 久久久久久久亚洲中文字幕 | 亚洲精品456在线播放app | 亚洲精华国产精华精| 桃色一区二区三区在线观看| xxx96com| 国产探花极品一区二区| 亚洲精品在线美女| 国产精品av视频在线免费观看| 亚洲av电影在线进入| 亚洲五月婷婷丁香| 看免费av毛片| 色噜噜av男人的天堂激情| 国产精品久久视频播放| 真人做人爱边吃奶动态| 日韩 欧美 亚洲 中文字幕| 欧美xxxx黑人xx丫x性爽| 国产色爽女视频免费观看| 精品人妻偷拍中文字幕| 69av精品久久久久久| 午夜久久久久精精品| 1000部很黄的大片| 国产精品精品国产色婷婷| 一区二区三区免费毛片| 国产精品久久久久久久电影 | 亚洲乱码一区二区免费版| 午夜福利欧美成人| 变态另类丝袜制服| 久久久久久久精品吃奶| 一本一本综合久久| 法律面前人人平等表现在哪些方面| 国产伦精品一区二区三区四那| 久久香蕉精品热| 欧美在线黄色| 90打野战视频偷拍视频| 成年人黄色毛片网站| 一卡2卡三卡四卡精品乱码亚洲| 天堂av国产一区二区熟女人妻| 精品不卡国产一区二区三区| 少妇人妻一区二区三区视频| 一二三四社区在线视频社区8| 中亚洲国语对白在线视频| 蜜桃亚洲精品一区二区三区| a级一级毛片免费在线观看| 午夜两性在线视频| 男女做爰动态图高潮gif福利片| 午夜亚洲福利在线播放| 九色国产91popny在线| 在线观看av片永久免费下载| 日本a在线网址| 国产aⅴ精品一区二区三区波| 每晚都被弄得嗷嗷叫到高潮| 亚洲七黄色美女视频| 日韩欧美国产在线观看| 最好的美女福利视频网| 俄罗斯特黄特色一大片| 亚洲精品色激情综合| 在线国产一区二区在线| 国产免费男女视频| 久久欧美精品欧美久久欧美| 亚洲精品美女久久久久99蜜臀| 久久天躁狠狠躁夜夜2o2o| 国产97色在线日韩免费| 波多野结衣巨乳人妻| 亚洲天堂国产精品一区在线| 老熟妇乱子伦视频在线观看| 精品国产超薄肉色丝袜足j| 欧美日韩综合久久久久久 | 国产精品,欧美在线| 成年人黄色毛片网站| 久久伊人香网站| 9191精品国产免费久久| 一区二区三区激情视频| 啦啦啦免费观看视频1| 日本a在线网址| 精品99又大又爽又粗少妇毛片 | 99国产综合亚洲精品| 午夜精品久久久久久毛片777| 国产av一区在线观看免费| 国内精品一区二区在线观看| 999久久久精品免费观看国产| 两个人的视频大全免费| 日韩 欧美 亚洲 中文字幕| 欧美性感艳星| 99久国产av精品| 欧美最新免费一区二区三区 | 男人舔奶头视频| 99国产综合亚洲精品| 亚洲成a人片在线一区二区| 91九色精品人成在线观看| 国产野战对白在线观看| 国产精品av视频在线免费观看| 麻豆国产97在线/欧美| 亚洲最大成人手机在线| 九色国产91popny在线| 免费av不卡在线播放| 一区福利在线观看| 日本免费a在线| 禁无遮挡网站| 国产97色在线日韩免费| 久久精品国产亚洲av香蕉五月| 精品免费久久久久久久清纯| 亚洲av免费高清在线观看| 男女那种视频在线观看| 精品不卡国产一区二区三区| 欧美午夜高清在线| 欧美xxxx黑人xx丫x性爽| 日韩欧美国产在线观看| 国产精品1区2区在线观看.| 亚洲第一电影网av| 夜夜夜夜夜久久久久| 一卡2卡三卡四卡精品乱码亚洲| 久久精品亚洲精品国产色婷小说| 中文字幕av成人在线电影| 免费高清视频大片| 精品久久久久久久末码| 国产久久久一区二区三区| 久久精品国产综合久久久| 夜夜看夜夜爽夜夜摸| www.色视频.com| 99riav亚洲国产免费| 黄色丝袜av网址大全| 波野结衣二区三区在线 | 午夜福利免费观看在线| xxx96com| 99久久精品热视频| 蜜桃亚洲精品一区二区三区| 人人妻,人人澡人人爽秒播| 性色avwww在线观看| 久久精品亚洲精品国产色婷小说| 亚洲精品国产精品久久久不卡| 精品99又大又爽又粗少妇毛片 | 悠悠久久av| 一个人观看的视频www高清免费观看| 日日摸夜夜添夜夜添小说| 婷婷六月久久综合丁香| 婷婷丁香在线五月| 午夜福利18| 好男人在线观看高清免费视频| 老熟妇乱子伦视频在线观看| 观看美女的网站| 99精品在免费线老司机午夜| 婷婷六月久久综合丁香| 欧美成人免费av一区二区三区| 伊人久久大香线蕉亚洲五| 国产成人影院久久av| 99国产精品一区二区三区| 床上黄色一级片| 天堂影院成人在线观看| 热99在线观看视频| 99久久综合精品五月天人人| 色在线成人网| 久久久久性生活片| 午夜福利高清视频| av女优亚洲男人天堂| 亚洲精品一卡2卡三卡4卡5卡| 国产精品精品国产色婷婷| 午夜精品一区二区三区免费看| 色噜噜av男人的天堂激情| 久久久久性生活片| 成人国产一区最新在线观看| 精品熟女少妇八av免费久了| 两个人的视频大全免费| 久久久色成人| 成年女人看的毛片在线观看| 黄片大片在线免费观看| 国产视频一区二区在线看| 狠狠狠狠99中文字幕| 日韩欧美在线乱码| 午夜福利免费观看在线| 麻豆一二三区av精品| 精品久久久久久,| 69av精品久久久久久| 真人做人爱边吃奶动态| 亚洲精品国产精品久久久不卡| 老师上课跳d突然被开到最大视频 久久午夜综合久久蜜桃 | 国产成人系列免费观看| 最新在线观看一区二区三区| 波多野结衣高清无吗| 成年人黄色毛片网站| 国产精品1区2区在线观看.| 午夜亚洲福利在线播放| 熟妇人妻久久中文字幕3abv| 俄罗斯特黄特色一大片| 欧美日本视频| av在线天堂中文字幕| 天堂av国产一区二区熟女人妻| 亚洲av免费在线观看| 亚洲第一电影网av| 国产高清激情床上av| 国产成人欧美在线观看| 亚洲中文字幕日韩| АⅤ资源中文在线天堂| 十八禁人妻一区二区| 1024手机看黄色片| 国产aⅴ精品一区二区三区波| 亚洲成人免费电影在线观看| 宅男免费午夜| 欧美乱妇无乱码| 波多野结衣巨乳人妻| 少妇人妻一区二区三区视频| 色播亚洲综合网| 亚洲在线自拍视频| 成年女人看的毛片在线观看| 啪啪无遮挡十八禁网站| 婷婷亚洲欧美| 亚洲欧美日韩卡通动漫| 国内精品一区二区在线观看| 欧美zozozo另类| 熟妇人妻久久中文字幕3abv| 国产黄色小视频在线观看| 在线播放无遮挡| 成人特级av手机在线观看| 怎么达到女性高潮| 老汉色av国产亚洲站长工具| 亚洲欧美日韩高清在线视频| 少妇的逼好多水| 亚洲av成人精品一区久久| 久久精品国产清高在天天线| 精品人妻一区二区三区麻豆 | 免费在线观看亚洲国产| 此物有八面人人有两片| 在线免费观看不下载黄p国产 | 日韩中文字幕欧美一区二区| 午夜福利视频1000在线观看| 国产午夜福利久久久久久| 十八禁人妻一区二区| 三级男女做爰猛烈吃奶摸视频| 欧美激情在线99| 日韩国内少妇激情av| 免费大片18禁| 又黄又粗又硬又大视频| 51午夜福利影视在线观看| 亚洲一区二区三区不卡视频| 在线观看美女被高潮喷水网站 | 国产视频一区二区在线看| 岛国在线免费视频观看| 99精品在免费线老司机午夜| 久久久成人免费电影| 免费在线观看亚洲国产| 精品国产亚洲在线| 丝袜美腿在线中文| 午夜日韩欧美国产| 国产真实伦视频高清在线观看 | 全区人妻精品视频| 久久久久久久久大av| 欧美成狂野欧美在线观看| 特级一级黄色大片| 在线免费观看的www视频| 午夜激情福利司机影院| 国产精品一区二区三区四区免费观看 | 五月伊人婷婷丁香| 亚洲七黄色美女视频| 制服人妻中文乱码| 国产精品影院久久| 欧美黑人巨大hd| 天堂av国产一区二区熟女人妻| 草草在线视频免费看| 色综合亚洲欧美另类图片| 99在线人妻在线中文字幕| 日本a在线网址| 黑人欧美特级aaaaaa片| 日韩欧美精品v在线| 禁无遮挡网站| 亚洲av中文字字幕乱码综合| 两个人的视频大全免费| 亚洲无线在线观看| 成人18禁在线播放| 国产免费一级a男人的天堂| 中文字幕熟女人妻在线| 最近最新中文字幕大全电影3| 神马国产精品三级电影在线观看| 在线观看午夜福利视频| 99久久成人亚洲精品观看| 最新在线观看一区二区三区| 国产亚洲精品av在线| www.色视频.com| 禁无遮挡网站| 国产成人啪精品午夜网站| 人人妻人人澡欧美一区二区| 国产美女午夜福利| 成人特级黄色片久久久久久久| 日韩av在线大香蕉| 国产精品亚洲美女久久久| 亚洲内射少妇av| 精品日产1卡2卡| 国产精品久久久久久亚洲av鲁大| 免费看十八禁软件| 国产午夜精品论理片| 美女高潮喷水抽搐中文字幕| 午夜福利成人在线免费观看| 午夜福利高清视频| 黄片大片在线免费观看| 欧美精品啪啪一区二区三区| 色综合站精品国产| 亚洲精品乱码久久久v下载方式 | 国产高清激情床上av| 非洲黑人性xxxx精品又粗又长| 又紧又爽又黄一区二区| 观看美女的网站| 日本一本二区三区精品| 日韩免费av在线播放| 欧美成人性av电影在线观看| 亚洲人成网站高清观看| 国产野战对白在线观看| 亚洲最大成人手机在线| 欧美高清成人免费视频www| 黄片小视频在线播放| 两人在一起打扑克的视频| 欧美最新免费一区二区三区 | 麻豆成人av在线观看| 久久香蕉国产精品| 欧美国产日韩亚洲一区| 神马国产精品三级电影在线观看| 久久久久九九精品影院| 麻豆国产av国片精品| 亚洲国产欧美网| 国产精品久久久久久精品电影| 一进一出抽搐动态| 在线十欧美十亚洲十日本专区| 天堂√8在线中文| 一卡2卡三卡四卡精品乱码亚洲| 97碰自拍视频| 在线观看午夜福利视频| 成人永久免费在线观看视频| 国产私拍福利视频在线观看| 99久久精品国产亚洲精品| 1000部很黄的大片| 天天躁日日操中文字幕| 国产伦在线观看视频一区| 国产精品综合久久久久久久免费| 69人妻影院| 精品国内亚洲2022精品成人| 国产精品香港三级国产av潘金莲| 毛片女人毛片| 免费无遮挡裸体视频| 综合色av麻豆| 中文字幕人妻熟人妻熟丝袜美 | 99热6这里只有精品| 大型黄色视频在线免费观看| 给我免费播放毛片高清在线观看| 国产精品98久久久久久宅男小说| 午夜福利在线观看吧| 国产精品一区二区三区四区免费观看 | 欧美激情在线99| 国产黄片美女视频| 久久天躁狠狠躁夜夜2o2o| 99视频精品全部免费 在线| 久久久久九九精品影院| 变态另类成人亚洲欧美熟女| www.色视频.com| 国内久久婷婷六月综合欲色啪| 国产精品久久久久久精品电影| 制服人妻中文乱码| 美女高潮喷水抽搐中文字幕| 免费在线观看日本一区| 国产精品一区二区三区四区久久| 欧美最黄视频在线播放免费| 欧美性猛交黑人性爽| 一区二区三区国产精品乱码| 亚洲av日韩精品久久久久久密| 9191精品国产免费久久| 欧美性猛交黑人性爽| 久久久久免费精品人妻一区二区| 一个人免费在线观看电影| 亚洲最大成人中文| 久久亚洲真实| 国产精品1区2区在线观看.| 99riav亚洲国产免费| 日韩中文字幕欧美一区二区| 高清毛片免费观看视频网站| 日本黄色视频三级网站网址| 国产成人影院久久av| 久久精品91蜜桃| 禁无遮挡网站| 成年女人看的毛片在线观看| 国产亚洲av嫩草精品影院| 国产精品久久久久久久电影 | 少妇高潮的动态图| 男女视频在线观看网站免费| 亚洲精品一卡2卡三卡4卡5卡| 嫩草影院入口| 国产乱人伦免费视频| 欧美成人一区二区免费高清观看| 国产视频一区二区在线看| 性色avwww在线观看| 欧美日韩综合久久久久久 | 国产亚洲精品一区二区www| 亚洲av日韩精品久久久久久密| 看黄色毛片网站| 欧美性猛交╳xxx乱大交人| 亚洲av中文字字幕乱码综合| 亚洲内射少妇av| 国产欧美日韩精品一区二区| 久久久国产精品麻豆| 淫妇啪啪啪对白视频| 99热只有精品国产| 精品国内亚洲2022精品成人| 91麻豆精品激情在线观看国产| 女人被狂操c到高潮| 国产不卡一卡二| 天堂影院成人在线观看| 丰满人妻一区二区三区视频av | 人妻夜夜爽99麻豆av| 亚洲欧美日韩高清专用| 亚洲中文字幕一区二区三区有码在线看| 国产亚洲精品久久久com| 在线a可以看的网站| 午夜福利在线观看吧| 欧美区成人在线视频| 给我免费播放毛片高清在线观看| 身体一侧抽搐| 一进一出抽搐动态| 日本五十路高清| 欧美3d第一页| 国产成人系列免费观看| 特大巨黑吊av在线直播| 日韩 欧美 亚洲 中文字幕| 国产成人啪精品午夜网站| 他把我摸到了高潮在线观看| 蜜桃久久精品国产亚洲av| 无遮挡黄片免费观看| 久久精品国产99精品国产亚洲性色| 色噜噜av男人的天堂激情| 国产aⅴ精品一区二区三区波| АⅤ资源中文在线天堂| 亚洲成av人片在线播放无| 国产高清有码在线观看视频| av福利片在线观看| 久久九九热精品免费| 国产高清视频在线播放一区| 在线免费观看不下载黄p国产 | 观看免费一级毛片| 亚洲熟妇熟女久久| 小蜜桃在线观看免费完整版高清| 免费看美女性在线毛片视频| 手机成人av网站| 午夜免费激情av| 国产精品综合久久久久久久免费| 国产视频内射| 一a级毛片在线观看| 最近最新中文字幕大全电影3| 亚洲精品粉嫩美女一区| 亚洲无线观看免费| 亚洲欧美日韩卡通动漫| 日本成人三级电影网站| 午夜精品久久久久久毛片777| 动漫黄色视频在线观看| 亚洲黑人精品在线| 天天一区二区日本电影三级| 欧美性猛交╳xxx乱大交人| 日日摸夜夜添夜夜添小说| АⅤ资源中文在线天堂| 天堂网av新在线| 国产精品三级大全| 99久久精品一区二区三区| 国产成人福利小说| 欧美乱码精品一区二区三区| 一夜夜www| 欧美日韩精品网址| 国产成人影院久久av| 麻豆久久精品国产亚洲av| 一进一出抽搐动态| 国产av麻豆久久久久久久| 在线观看一区二区三区| 精品人妻一区二区三区麻豆 | 国产三级中文精品| 18禁黄网站禁片午夜丰满| 波多野结衣高清无吗| 国产亚洲欧美98| 在线视频色国产色| 精品99又大又爽又粗少妇毛片 | 亚洲人成网站高清观看| 长腿黑丝高跟| 国产亚洲精品久久久com| 国内少妇人妻偷人精品xxx网站| 亚洲人成伊人成综合网2020| 久久人人精品亚洲av| 成年女人毛片免费观看观看9| 国产一区二区在线观看日韩 | 天天一区二区日本电影三级| 99久久无色码亚洲精品果冻| av天堂中文字幕网| 午夜免费激情av| 色哟哟哟哟哟哟| 操出白浆在线播放| 午夜免费成人在线视频| 蜜桃亚洲精品一区二区三区| 搡女人真爽免费视频火全软件 | 午夜激情福利司机影院| 午夜影院日韩av| 校园春色视频在线观看| 丰满的人妻完整版| 99热这里只有是精品50| 国产亚洲欧美在线一区二区| 99久久99久久久精品蜜桃| 51午夜福利影视在线观看| 国产乱人伦免费视频| 国产亚洲av嫩草精品影院|