scholarly journals Inhibin B is a more sensitive marker of spermatogenetic damage than FSH in the irradiated non-human primate model

1999 ◽  
Vol 162 (3) ◽  
pp. 393-400 ◽  
Author(s):  
L Foppiani ◽  
S Schlatt ◽  
M Simoni ◽  
GF Weinbauer ◽  
U Hacker-Klom ◽  
...  

This study evaluated the effect of bilateral testicular irradiation (2 Gy) on reproductive hormones, testicular volume (TV) and sperm parameters in six adult cynomolgus monkeys. Hormone levels (FSH, inhibin B and testosterone (T)) were determined to find the most valuable endocrine marker of irradiation-induced damage. All parameters were analysed at weekly intervals for 14 weeks. Histological evaluation of both testes was performed at week 14 after irradiation when one monkey was castrated and at week 27 when the remaining five monkeys were bilaterally biopsied. A decrease in body weight, TV (30% of the pre-treatment size) and sperm count was observed after irradiation. Severe oligozoospermia was achieved throughout the study but azoospermia was recorded only occasionally. Histological evaluation revealed a heterogeneous picture with patchy arrangement of seminiferous tubules containing advanced germ cell types. An increase (P<0.05) in FSH levels and, to a lesser degree also in T levels, occurred several weeks after irradiation. Inhibin B levels showed a sharp decline (P<0.001) as soon as 1 week after irradiation. FSH and inhibin B did not return to baseline levels during the observation period. A negative correlation was found between FSH and inhibin B values (r=-0.35, P<0.001). Inhibin B correlated positively with testis volume (r=0.73, P<0.001) and sperm counts (r=0.55, P<0.01). In conclusion, this study shows that inhibin B represents an early and more sensitive marker of testicular damage than FSH. Furthermore, the rapid fall of inhibin B after irradiation suggests that this hormone is a direct parameter of premeiotic germ cell proliferation.

2006 ◽  
Vol 91 (7) ◽  
pp. 2732-2737 ◽  
Author(s):  
Katharina M. Main ◽  
Jorma Toppari ◽  
Anne-Maarit Suomi ◽  
Marko Kaleva ◽  
Marla Chellakooty ◽  
...  

Abstract Context: Recent studies showed that male reproductive health problems, such as cryptorchidism, hypospadias, testicular cancer, and low sperm quality, are more prevalent in Denmark than in Finland. Objectives: We hypothesized that, if fetal testicular dysgenesis contributed to these observations, differences in gonadal development and the hypothalamus-pituitary-testis axis would already be detectable perinatally. Thus, we investigated healthy newborn boys in both countries. Design: This was a prospective, longitudinal population-based study. Setting: Two primary obstetric centers were included at the University Hospitals of Copenhagen, Denmark, and Turku, Finland. Participants: The participants of the study included 633 Danish and 1044 Finnish boys, born at term with appropriate weight for gestational age. Interventions: Ultrasound determination of testis size at 0, 3, and 18 months and blood sampling (n = 727) at 3 months were analyzed. Main Outcome Measures: Testicular volume and reproductive hormones were measured. Results: Testis volume was significantly higher at all ages in Finnish than in Danish boys (medians, 98 vs. 95, 185 vs. 119, and 188 vs. 136 mm3, respectively; P &lt; 0.00001). Testis growth from birth to 3 months was larger in Finnish than in Danish boys (mean, 75 vs. 26 mm3; P &lt; 0.0001). Serum hormone levels were higher in Finnish than Danish boys for inhibin B (median, 456 vs. 385 pg/ml; P &lt; 0.0001), FSH (1.33 vs. 1.21 IU/liter; P &lt; 0.036), and SHBG (143 vs. 136 nmol/liter; P &lt; 0.022). Inhibin B was significantly positively correlated to testicular volume (r = 0.25; P &lt; 0.006). Conclusions: The larger testes and higher inhibin B levels most likely represent a bigger volume of seminiferous tubules in Finnish compared with Danish boys. Although this phenomenon may be attributable to a genetic difference between the two countries, it may also reflect environmental factors influencing testicular development.


Reproduction ◽  
2016 ◽  
Vol 152 (5) ◽  
pp. 379-388 ◽  
Author(s):  
Jonathan T Busada ◽  
Ellen K Velte ◽  
Nicholas Serra ◽  
Kenneth Cook ◽  
Bryan A Niedenberger ◽  
...  

We previously described a novel germ cell-specific X-linkedreproductivehomeoboxgene (Rhox13) that is upregulated at the level of translation in response to retinoic acid (RA) in differentiating spermatogonia and preleptotene spermatocytes. We hypothesize that RHOX13 plays an essential role in male germ cell differentiation, and have tested this by creating aRhox13gene knockout (KO) mouse.Rhox13KO mice are born in expected Mendelian ratios, and adults have slightly reduced testis weights, yet a full complement of spermatogenic cell types. Young KO mice (at ~7–8 weeks of age) have a ≈50% reduction in epididymal sperm counts, but numbers increased to WT levels as the mice reach ~17 weeks of age. Histological analysis of testes from juvenile KO mice reveals a number of defects during the first wave of spermatogenesis. These include increased apoptosis, delayed appearance of round spermatids and disruption of the precise stage-specific association of germ cells within the seminiferous tubules. Breeding studies reveal that both young and aged KO males produce normal-sized litters. Taken together, our results indicate that RHOX13 is not essential for mouse fertility in a controlled laboratory setting, but that it is required for optimal development of differentiating germ cells and progression of the first wave of spermatogenesis.


2018 ◽  
Vol 243 (11) ◽  
pp. 917-925 ◽  
Author(s):  
Elisa G Santos ◽  
Maraisa A Silva ◽  
Renata P Amorim ◽  
Leticia de Souza Giordano ◽  
Dayana de Sales Silva ◽  
...  

The chromatoid body is a cytoplasmic male germ cell structure that plays a role in the regulation of mRNA transcription during spermatogenesis. A proteomic analysis of this structure has identified the presence of its classic molecular markers (MVH and MIWI), as well as a significant number of transient proteins. Circadian locomotor output cycles protein kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1), which are molecular components of the circadian clock, are likely located in the chromatoid body in a transient fashion. This study sought to determine whether aging produces morphological changes in the chromatoid bodies of round spermatids similar to those previously observed in BMAL1 knockout mice. A sample of 30 male mice was divided into three groups: juvenile mice (45 days old), adult mice (120 days old), and old mice (+180 days old). Aging was confirmed by viability and sperm count analyses and testosterone dosage. Squash slides prepared with fragments of seminiferous tubules were immunostained for MVH, MIWI, BMAL1, and CLOCK detection. In juvenile and adult specimens, single round chromatoid bodies were observed using MVH/BMAL1 and MIWI/CLOCK immunostaining. In old specimens, many chromatoid bodies displayed changes in number and morphology, as well as an increase in the interactions between MVH and BMAL1; MIWI and CLOCK. Changes in chromatoid body morphology increased interactions between the proteins analyzed herein, and decreased amounts of these proteins in seminiferous tubules of older mice may indicate that aging influences the assembly and physiology of chromatoid bodies, which may, in turn, affect fertility. Impact statement The results discussed in this paper indicate that aging compromises the structure and physiology of chromatoid bodies (CBs) in post-meiotic male cells. Since CB is a fundamental structure for the differentiation of the mature male germ cell it is possible that this imbalance in CB physiology may play a role in the reduction of fertility in older men. It is important to note that not only the classic CB markers (such as the MIWI and MVH proteins) were used to showcase the structural changes in the CBs but also the main components of circadian cycle control (the CLOCK and BMAL1 proteins), indicating that the reduction of circadian control in aged males may contribute to these changes in CBs as well. Therefore, it is intriguing to evaluate the hypothesis that controlling these physiological/structural changes in CBs may be a way of delaying the effects of aging in males.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Amr Amin ◽  
Christeena Abraham ◽  
Alaaeldin A. Hamza ◽  
Zeinab A. Abdalla ◽  
Shaikha B. Al-Shamsi ◽  
...  

The aim of this study was to evaluate the protective effects ofGinkgo biloba(GB) against testicular damage and oxidative stress as well as caudal sperm indices in a cisplatin- (CIS-) induced rodent model. Adult male Wistar rats were given vehicle, single i.p. dose of CIS alone (10 mg/kg), GB alone (200 mg g/kg every day for five days), or single dose of CIS followed by GB (50, 100, or 200 mg/kg every day for five days). On day 6, after the first drug treatment oxidative and apoptotic testicular toxicity was evaluated. CIS-treated rats displayed decreased weights of testes and epididymis as well as caudal sperm count and motility. This reproductive toxicity was accompanied with increased germ-cell degeneration in seminiferous tubules and increased germ-cell apoptosis, increased testicular MDA levels and MPO activity, and decreased SOD and CAT activities in testes. Intensive expressions of COX-2, iNOS, and NF-κB p65 in testicular tissues were detected in CIS-treated group. Oral GB administrations at all doses to CIS-treated rats effectively alleviated all of the CIS-induced toxicity in reproductive system. The present results provide further insights into the mechanisms of protection against CIS-induced reproductive toxicity and confirm the essential antioxidant potential of a GB extract.


Author(s):  
Alfonsina Morales ◽  
Juan C. Cavicchia

The present investigation was under taken, combining the identification of specific germ cell types present in a particular stage of the seminiferous wave with freeze-fracture techniques to follow the changing pattern of their nuclear pore distribution during spermatogenesis. Male albino adult rats were used. Segments of seminiferous tubules were separated (stages VII-VIII; IX-XI; XII-XIV) by a technique described by Parvinen and Vanha-Perttula where the stages of the cycle were recognized and isolated by transillumination under a dissecting microscope. The tubular segments were immediately fixed in glutaraldehyde, immersed in glycerol, freeze-fractured in a Balzers BAF 301 apparatus at-110°C and examined under a Siemens Elmiskop I EM. The only spermatogonia located in the studied stages (type A) are ovalcells in contact with the basal lamina. Pore distribution is non-random with a relatively in conspicuous aggregation. Preleptotene spermatocytes (stages VII-VIII) are easily identified by being numerous, their location over the basal lamina and the irrelatively small size. They exhibit a striking clustering of pores, in groups of 15-30 separated by pore-free areas (fig.1). Leptotenes (fig.2, 3) (stages IX-XI) and zygotenes (fig.4) (XII-XIII) change the pattern to a more even distributional though clearly maintaining some degree of clustering.


1998 ◽  
Vol 83 (4) ◽  
pp. 1284-1291 ◽  
Author(s):  
Yang Zhengwei ◽  
Nigel G. Wreford ◽  
Peter Royce ◽  
David M. de Kretser ◽  
Robert I. McLachlan

Testosterone (T) treatment suppresses gonadotropin levels in normal men and is a promising reversible contraceptive that induces azoospermia in approximately 70% of subjects and oligospermia in the remainder; however, the basis of this variable response is unclear. This study aimed to investigate this reported variable response by examining the spermatogenic process and quantitating germ cell number in men after T-induced gonadotropin withdrawal. Ten normal fertile men (31–46 yr), already planning to undergo vasectomy, either received T enanthate (200 mg, im, weekly) for 19–24 weeks (n = 5; TE group) or proceeded directly to surgery (n = 5; controls), at which time a unilateral testicular biopsy was taken, and germ cell numbers were estimated using the optical disector stereological method. In response to TE treatment, serum T levels rose 2-fold, and FSH/LH levels became undetectable. Sperm counts fell to azoospermia in 4 men and to 21 million/mL in the fifth man. The mean number of type A spermatogonia per 100 Sertoli cells was unchanged, but type B spermatogonia fell markedly to 10% of the control values, and later germ cell types decreased to 11–18% of the control values. The pattern of germ cell suppression varied widely and showed no relationship with sperm count or the time to azoospermia. Despite the presence of elongated spermatids (1.4–20% of the control), four men remained azoospermic. Two TE subjects with similar early germ cell complements and elongated spermatid numbers had sperm counts of zero and 21 million/mL; the latter man demonstrated marked variability in germ cell numbers between adjacent tubules. We conclude that 1) the principal spermatogenic lesion in TE-treated men is the marked (90%) inhibition of type A→B spermatogonial maturation. Other sites are also affected, particularly the release and/or survival of elongated spermatids during transit; and 2) a steady state in germ cell number may not be established even after 4–5 months of TE treatment. The findings suggest that TE treatment does not adequately or consistently withdraw hormonal support for spermatogenesis, leading to variable between- and within-individual patterns of germ cell suppression.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Godwin Adakole Ujah ◽  
Victor Udo Nna ◽  
Joseph Bagi Suleiman ◽  
Chinedum Eleazu ◽  
Chukwuemeka Nwokocha ◽  
...  

AbstractDoxorubicin (DOX) is a broad-spectrum chemotherapeutic drug used in the treatment of cancers. It acts by generating reactive oxygen species in target cells. The actions are, however, not limited to cancerous cells as it attacks healthy cells, killing them. This study investigated the benefits of the antioxidant, tert-butylhydroquinone (tBHQ), on testicular toxicity following DOX therapy. Twenty-four adult male albino rats were assigned randomly into four groups (n = 6), namely: normal control (NC), tBHQ, DOX and tBHQ + DOX groups. tBHQ (50 mg/kg body weight in 1% DMSO) was administered orally for 14 consecutive days, while a single DOX dose (7 mg/kg body weight) was administered intraperitoneally on Day 8. DOX decreased sperm count, motility and viability, and decreased the levels of steroidogenesis-related proteins, and reproductive hormones. Furthermore, DOX decreased the expression of antioxidant cytoprotective genes, and decreased the protein level of proliferating cell nuclear antigen in the testis. Conversely, DOX increased the expression of pro-inflammatory and pro-apoptotic genes in the testis. These negative effects were ameliorated following the intervention with tBHQ. Our results suggest that tBHQ protects the testis and preserves both steroidogenesis and spermatogenesis in DOX-treated rats through the suppression of oxidative stress, inflammation and apoptosis.


2003 ◽  
Vol 22 (3) ◽  
pp. 159-174 ◽  
Author(s):  
Jon N. Cammack ◽  
Randy D. White ◽  
Donovan Gordon ◽  
Jerome Gass ◽  
Lawrence Hecker ◽  
...  

Di-(2-ethylhexyl)phthalate (DEHP) was administered to 3- to 5-day-old male Sprague-Dawley rats by daily intravenous injections of 60, 300, or 600 mg/kg/day or by daily oral gavage of 300 or 600 mg/kg/day for 21 days. Histopathological evaluation and organ weight measurements were performed on some animals after 21 days of dosing (primary group) and later on the recovery group animals that were held without further treatment until sexual maturity at approximately 90 days of age. No effects of any type were observed in animals treated intravenously with 60 mg/kg/day. Testicular changes, consisting of a partial depletion of the germinal epithelium and/or decrease in diameter of seminiferous tubules, were present in all animals of the 300- and 600-mg/kg/day groups after the 21-day dosing period. Testes weight decreased and liver weight increased in these animals. Testes changes were dose-related and generally more severe among animals dosed orally versus intravenously. In the recovery animals, a residual DEHP-induced decrease in seminiferous tubule diameter was present in the testis of several animals dosed orally at 300 and 600 mg/kg/day, but not in animals dosed intravenously. There was no germinal cell depletion or Sertoli cell alteration observed in any dose group at any time. Notably, no effects on sperm count, sperm morphology, or sperm motility were observed at 90 days of age in any of the groups.


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