Decline In Spermatogenesis Research Articles

Germ cell progression through zebrafish spermatogenesis declines with age.

Vertebrate spermatogonial stem cells maintain sperm production over the lifetime of an animal but fertility declines with age. While morphological studies have informed our understanding of typical spermatogenesis, the molecular and cellular mechanisms underlying the maintenance and decline of spermatogenesis are not yet understood. We used single-cell RNA sequencing to generate a developmental atlas of the aging zebrafish testis. All testes contained spermatogonia, but we observed a progressive decline in spermatogenesis that correlates with age. Testes from some older males only contained spermatogonia and a reduced population of spermatocytes. Spermatogonia in older males are transcriptionally distinct from spermatogonia in testes capable of robust spermatogenesis. Immune cells including macrophages and lymphocytes drastically increase in abundance in testes that cannot complete spermatogenesis. Our developmental atlas reveals the cellular changes as the testis ages and defines a molecular roadmap for the regulation of spermatogenesis.

Age-related elevation of O-GlcNAc causes meiotic arrest in male mice

In recent years, the postponement of childbearing has become a critical social issue. Male fertility is negatively associated with age because of testis aging. Spermatogenesis is impaired with age, but the molecular mechanism remains unknown. The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging.

Severing the ventral funiculus in chronic spinal cord injury has the most deteriorating effect on spermatogenesis in rats.

Sexual dysfunction, following spinal cord injury (SCI), is highly dependent on the extent of injury. SCI disrupts the supraspinal innervation of the reproductive organs; resulting in structural and functional deficits. Relating the extent of SCI to these changes could eventually improve diagnoses and treatment planning of sexual dysfunction following SCI. In the present study, following chronic SCI of different severities (1/3 dorsal SCI (1/3 SCI), 2/3 dorsal SCI (2/3 SCI), and complete transection (Tx)) at T8 spinal level, histological changes of seminiferous tubules parameters in testis were examined. The diameter of seminiferous tubules (DST) and epithelial height of seminiferous tubules (HST) were significantly decreased in all SCI groups compared to control and sham. In addition, DST in 2/3 SCI and Tx groups and HST in Tx group were significantly decreased in comparison with 1/3 SCI animals. Nonetheless, the diameter of seminiferous tubules' lumen decreased significantly in 2/3 SCI and Tx compared to control, sham, and 1/3 SCI groups. Concerning cellular component, the number of spermatocytes and spermatids layers significantly decreased in both 1/3 and 2/3 SCI in comparison to normal. However, Tx had the most prominent deteriorating effect on these layers; indicating impairment in the process of spermatogenesis. These results show that the spinal tracts are part of the neural circuitries innervating the testis and responsible for their structural support. These tracts are mainly distributed between the lateral and ventral funiculi at T8 spinal level. Consequently, sparing ventral funiculi in the SCI prevents the severe decline in spermatogenesis.

Sirtuins: Novel Players in Male Reproductive Health.

The current lifestyle of "western societies" is based on excessive consumption of high-energy diets and physical inactivity. Such behavior has pressured biological systems towards the development of metabolic diseases. This increased incidence of metabolic disorders is also accompanied by a decline in male reproductive health, particularly among young males. Male fertility is sensitive to metabolic dysfunctions, such as diabetes mellitus, which disrupt the link between energy metabolism and reproduction. Evidences showed that compromised sperm parameters induced by diabetes are associated with impaired testicular metabolism, suggesting that deficient testicular bioenergetics contributes to a decline in spermatogenesis. Energy metabolism is a well-coordinated process that involves a network of carbohydrate, lipid and protein metabolic pathways. This intricate process is an act of balance between mitochondria and nucleus, governed by metabolic sensors, such as sirtuins. The emerging role of sirtuins in the control of metabolism has been highlighted, specially in cancer metabolism. Little attention has been given to their role in non-cancerous cells that exhibit a "Warburg-like metabolism", such as Sertoli cells. Spermatogenesis is highly dependent on glycolytic metabolism, since the lactate produced by Sertoli cells is the major substrate of germ cells. The regulation of sirtuins in the glycolytic metabolism not only increases their physiological relevance to the testicular environment, but also suggests that these proteins may control male fertility. This review will discuss the recent findings in the role of sirtuins in testicular metabolism and will address the concept that sirtuins can be a potential target to counteract subfertility/infertility promoted by diabetes mellitus.

Centrosome misorientation reduces stem cell division during ageing

Asymmetric division of adult stem cells generates one self-renewing stem cell and one differentiating cell, thereby maintaining tissue homeostasis. A decline in stem cell function has been proposed to contribute to tissue ageing, although the underlying mechanism is poorly understood. Here we show that changes in the stem cell orientation with respect to the niche during ageing contribute to the decline in spermatogenesis in the male germ line of Drosophila. Throughout the cell cycle, centrosomes in germline stem cells (GSCs) are oriented within their niche and this ensures asymmetric division. We found that GSCs containing misoriented centrosomes accumulate with age and that these GSCs are arrested or delayed in the cell cycle. The cell cycle arrest is transient, and GSCs appear to re-enter the cell cycle on correction of centrosome orientation. On the basis of these findings, we propose that cell cycle arrest associated with centrosome misorientation functions as a mechanism to ensure asymmetric stem cell division, and that the inability of stem cells to maintain correct orientation during ageing contributes to the decline in spermatogenesis. We also show that some of the misoriented GSCs probably originate from dedifferentiation of spermatogonia.

Adverse effects of rosemary (Rosmarinus officinalis L.) on reproductive function in adult male rats.

Ingestion of rosemary (Rosmarinus officinalis L.) by two groups of adult Sprague-Dawley rats at levels of 250 and 500 mg/kg body wt for 63 days was investigated for its effects on fertility. Body weight and absolute and relative testes weights were not affected, but the average weights of epididymides, ventral prostates, seminal vesicles, and preputial glands decreased significantly. A significant decline in spermatogenesis in testes due to a decrease in the number of primary and secondary spermatocytes and spermatids in treatment group 2 (500 mg/kg) is attributed to a significant decrease in testosterone. Sperm motility and density were also significantly decreased in the cauda epididymis and in the testes of rosemary-treated male rats in group 2. In addition, the treatment markedly increased the number of fetal resorptions in female rats impregnated by group 2 males, thereby reducing their fertility.

Penile vibratory stimulation and electroejaculation in the treatment of ejaculatory dysfunction.

The purpose of this review is to present the current understanding of penile vibratory stimulation (PVS) and electroejaculation (EEJ) procedures and its clinical use in men with ejaculatory dysfunction. Unfortunately, the record of treating such individuals has been quite poor, but within recent years development and refinement of PVS and EEJ in men with spinal cord injury (SCI) has significantly enhanced the prospects for treatment of ejaculatory dysfunction. The majority of spinal cord injured men are not able to produce antegrade ejaculation by masturbation or sexual stimulation. However, approximately 80% of all spinal cord injured men with an intact ejaculatory reflex arc (above T10) can obtain antegrade ejaculation with PVS. Electroejaculation may be successful in obtaining ejaculate from men with all types of SCI, including men who do not have major components of the ejaculatory reflex arc. Because vibratory stimulation is very simple in use, non-invasive, it does not require anaesthesia and is preferred by the patients when compared with EEJ, PVS is recommended to be the first choice of treatment in spinal cord injured men. Furthermore, EEJ has been successfully used to induce ejaculation in men with multiple sclerosis and diabetic neuropathy. Any other conditions which affect the ejaculatory mechanism of the central and/or peripheral nervous system including surgical nerve injury may be treated successfully with EEJ. Finally, for sperm retrieval and sperm cryopreservation before intensive anticancer therapy in pubertal boys, PVS and EEJ have been successfully performed in patients who failed to obtain ejaculation by masturbation. Nearly all data concerning semen characteristics in men with ejaculatory dysfuntion originate from spinal cord injured men. Semen analyses demonstrate low sperm motility rates in the majority of spinal cord injured men. The data give evidence of a decline in spermatogenesis and motility of ejaculated spermatozoa shortly after (few weeks) an acute SCI. Furthermore, it is suggested that some factors in the seminal plasma and/or disordered storage of spermatozoa in the seminal vesicles are mainly responsible for the impaired semen profiles in men with chronic SCI. Home insemination with semen obtained by penile vibratory and introduced intravaginally in order to achieve successful pregnancies may be an option for some spinal cord injured men and their partners. The majority of men will further enhance their fertility potential when using either penile vibratory or EEJ combined with assisted reproduction techniques such as intrauterine insemination or in-vitro fertilization with or without intracytoplasmic sperm injection.

Sexual function in spinal cord lesioned men.

Review of literature. To review the physical aspects related to penile erection, ejaculatory dysfunction, semen characteristics, and techniques for enhancement of fertility in spinal cord lesioned (SCL) men. Worldwide: individuals with traumatic as well as non-traumatic SCL. Recommendations for management of erectile dysfunction in SCL men: If it is possible to obtain a satisfactory erection but of insufficient duration, then try to use a venous constrictor band to find out if this is sufficient to maintain the erection. Otherwise we recommend Sildenafil. If Sildenafil is not satisfactory then use intracavernous injection with prostaglandin E(1) (some SCL men may prefer cutaneous or intraurethral application). We discourage the implantation of penile prosthesis for the sole purpose of erection. Recommendations for management of ejaculatory dysfunction in SCL men: Penile vibratory stimulation (PVS) to induce ejaculation is recommended as first treatment choice. If PVS fails, SCL men should be referred for electroejaculation (EEJ). Semen characteristics: Impaired semen profiles with low motility rates are seen in the majority of SCL men. Recently reported data gives evidence of a decline in spermatogenesis and motility of ejaculated spermatozoa shortly after (few weeks) an acute SCL. It is suggested that some factors in the seminal plasma and/or disordered storage of spermatozoa in the seminal vesicles are mainly responsible for the impaired semen profiles in men with chronic SCL. Fertility: Home insemination with semen obtained by PVS and introduced intravaginally in order to achieve successful pregnancies may be an option for some SCL men and their partners. The majority of SCL men will further enhance their fertility potential when using either PVS or EEJ combined with assisted reproduction techniques such as intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection.

Effects of long-term continuous GnRH administration on the pituitary–gonadal axis in Eld's deer stags (Cervus eldi thamin)

Eld's deer stags (Cervus eldi thamin) (in groups of three) were continuously administered gonadotropin-releasing hormone (GnRH) in control, low, medium, or high doses (0, 20.1 ± 0.7, 83.3 ± 2.6, and 292.9 ± 4.9 ng∙kg−1∙d−1, respectively) via osmotic minipumps for ~80 d to investigate the potential for precociously reactivating the pituitary–testicular axis during the nonbreeding season. Secretory patterns of LH, FSH, and testosterone concentrations were qualitatively similar among treatments. However, in the low-dose group, basal LH and FSH concentrations were both increased (p < 0.05) and pituitary responsiveness to a superimposed GnRH challenge was augmented (p < 0.05) after 12 weeks of treatment compared with all other groups. Despite these endocrine changes, continuous low-dose GnRH administration was not effective for precociously inducing testicular activity in this seasonally breeding species. High-dose GnRH administration initially induced a transient increase in LH, FSH, and testosterone secretion and delayed, but did not prevent, the seasonal decline in spermatogenesis. After 6–12 weeks of high-dose GnRH administration, however, attenuated pituitary responsiveness appeared to delay the normal seasonal reactivation of the pituitary–gonadal axis. In conclusion, prolonged, continuous low-dose GnRH administration did not effectively translate into a precocious onset of testicular activity; therefore, this specific approach is unlikely to be useful for prolonging the fertile period in this seasonally breeding species.

Enhanced daily sperm production in the remaining testis of aged rats following hemicastration.

To investigate the effects of age and hemicastration on daily sperm production (DSP), testes from adult (6 to 10 months) and aged (22 to 24 months) Sprague‐Dawley rats were evaluated before and four months after hemicastration. Testes were weighted, decapsulated, homogenized in a Waring Blender, and evaluated for the number of maturation‐phase spermatids in the homogenates. DSP per testis was calculated by dividing the number of spermatids in the homogenates by the estimated life span of the spermatids (6.3 days). The same testicular traits, along with plasma LH and FSH levels, were determined in a second group of aged rats. Considering both testes in the first experiment, neither DSP per testis nor DSP per g parenchyma were significantly affected by age. However, the age testis interaction was significant (P < 0.01) in both parameters. DSP per g of the testis removed at hemicastration was slightly lower (P < 0.05) in the aged group, and DSP per g in the aged rat was enhanced (P < 0.05) in the hemicastrates. Unlike the adults, aged rats had enhanced (P < 0.01) DSP per testis in the remaining testis posthemicastration. In the second experiment, testicular weight, DSP per g, and DSP per testis were enhanced (P < 0.01) after hemicastration. Plasma FSH levels were significantly (P < 0.01) elevated within one week after hemicastration and remained elevated four months later. Plasma LH levels were not elevated within one week after hemicastration but were significantly (P < 0.01) elevated four months following hemicastration.We concluded that: 1. measured by DSP, no decline in spermatogenesis was found between 6 to 10 and 22 to 24 months of age; 2. aged rats were capable of hemicastration‐induced testicular enlargement and enhancement of DSP, 3. rats in the adult group were not capable of these hemicastration‐induced changes, 4. posthemicastration testicular enlargement was accompanied by an increased number of germ cells; 5. immediate and continued elevation of plasma FSH suggests its involvement in hemicastration‐induced testicular enlargement of aged rats.

The effects of depressed pH on spermatogenesis in flagfish Jordanella floridae

Mature male flagfish Jordanella floridae were continuously exposed to lake water with depressed pH levels of 6.0, 5.5, 5.0 and 4.5 during a 20 day period at 25°C. Quantitative histological analysis based upon the final stage of spermatogenesis prior to sperm formation indicated that the production of mature sperm was reduced at all pH values tested by 24.03, 27.03, 37.28 and 35.29% respectively when compared with the control at pH 6.7. Total volume of reproductive tissue relative to somatic tissue within the testes showed similar declines of 24.64, 25.39, 24.81 and 38.50% respectively compared to the control. The general decline in spermatogenesis was confirmed morphologically by increased occurrence of tubules devoid of sperm and was particularly evident at pH 4.5. Comparison of the present results with data from female ovaries of the same experiment suggests a higher sensitivity of developing eggs to declining pH when compared with developing sperm.

The Reproduction of the Wild Rabbit Oryctolagus cuniculus (L.).

The Reproduction of the Wild Rabbit <i>Oryctolagus cuniculus</i> (L.).