Endocrine Disruptors and Leydig Cell Function

During the past decades, a large body of information concerning the effects of endocrine disrupting compounds (EDCs) on animals and humans has been accumulated. EDCs are of synthetic or natural origin and certain groups are known to disrupt the action of androgens and to impair the development of the male reproductive tract and external genitalia. The present overview describes the effects of the different classes of EDCs, such as pesticides, phthalates, dioxins, and phytoestrogens, including newly synthesized resveratrol analogs on steroidogenesis in Leydig cells. The potential impact of these compounds on androgen production by Leydig cells during fetal development and in the adult age is discussed. In addition, the possible role of EDCs in connection with the increasing frequency of abnormalities in reproductive development in animals and humans is discussed.

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Estrogen-Dependent and -Independent Estrogen Receptor-α Signaling Separately Regulate Male Fertility

Endocrinology ◽

10.1210/en.2008-1016 ◽

2009 ◽

Vol 150 (6) ◽

pp. 2898-2905 ◽

Cited By ~ 46

Author(s):

Kerstin W. Sinkevicius ◽

Muriel Laine ◽

Tamara L. Lotan ◽

Karolina Woloszyn ◽

John H. Richburg ◽

...

Keyword(s):

Estrogen Receptor ◽

Male Fertility ◽

Reproductive Tract ◽

Cell Function ◽

Critical Role ◽

Estrogen Receptor Α ◽

Male Reproductive Tract ◽

Efferent Ductule

Estrogen receptor-α (ERα) plays a critical role in male reproductive tract development and fertility. To determine whether estrogen-dependent and -independent ERα mechanisms are involved in male fertility, we examined male estrogen nonresponsive ERα knock-in mice. These animals have a point mutation (G525L) in the ligand-binding domain of ERα that significantly reduces interaction with, and response to, endogenous estrogens but does not affect growth factor activation of ligand-independent ERα pathways. Surprisingly, we found that ligand-independent ERα signaling is essential for concentrating epididymal sperm via regulation of efferent ductule fluid reabsorption. In contrast, estrogen-dependent ERα signaling is required for germ cell viability, most likely through support of Sertoli cell function. By treating estrogen nonresponsive ERα knock-in (ENERKI) mice with the ERα selective synthetic agonist propyl pyrazole triol, which is able to bind and activate G525L ERα in vivo, we discovered male fertility required neonatal estrogen-mediated ERα signaling. Thus, our work indicates both estrogen-dependent and -independent pathways play separable roles in male murine reproductive tract development and that the role of ERα in human infertility should be examined more closely.

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The Effect of PDE5 Inhibitors on the Male Reproductive Tract

Current Pharmaceutical Design ◽

10.2174/1381612826666200226121510 ◽

2020 ◽

Vol 26 ◽

Cited By ~ 2

Author(s):

Nikolaos Sofikitis ◽

Aris Kaltsas ◽

Fotios Dimitriadis ◽

Jens Rassweiler ◽

Nikolaos Grivas ◽

...

Keyword(s):

Male Infertility ◽

Reproductive Tract ◽

Tunica Albuginea ◽

Scientific Data ◽

Secretory Function ◽

Pde5 Inhibitors ◽

Male Reproductive Tract ◽

Review Study ◽

Phosphodiesterase 5

The therapeutic range of cyclic nucleotide phosphodiesterase 5 inhibitors (PDE5) inhibitors is getting wider in the last years. This review study focuses on the potential employment of PDE5 inhibitors as an adjunct tool for the therapeutic management of male infertility. The literature tends to suggest a beneficial effect of PDE5 inhibitors on Leydig and Sertoli cells secretory function. It also appears that PDE5 inhibitors play a role in the regulation of the contractility of the testicular tunica albuginea and the epididymis. Moreover scientific data suggest that PDE5 inhibitors enhance the prostatic secretory function leading to an improvement in sperm motility. Other studies additionally demonstrate a role of PDE5 inhibitors in the regulation of sperm capacitation process. Placebo-controlled, randomized, blind studies are necessary to unambiguously incorporate PDE5 inhibitors as an adjunct tool for the pharmaceutical treatment of semen disorders and male infertility.

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Carboxylesterase overexpression in the male reproductive tract: a universal safeguarding mechanism?

Reproduction Fertility and Development ◽

10.1071/rd99011 ◽

1999 ◽

Vol 11 (3) ◽

pp. 133 ◽

Cited By ~ 16

Author(s):

A. T. Mikhailov ◽

M. Torrado

Keyword(s):

Reproductive Tract ◽

Expression Patterns ◽

Cell Lineage ◽

Environmental Chemicals ◽

Male Reproductive Tract ◽

Morphological Organization ◽

Associated Functions ◽

And Function ◽

Hypothetical Explanation

Data on expression patterns of carboxylesterases in the male reproductive tract of different animal groups (i.e. bivalve mollusks, fruitflies and rodents) are summarized to highlight some particularly interesting questions in the context of sperm differentiation, maturation and function. The male reproduc-tive system, in spite of extreme variation in the anatomical/morphological organization in different species, is characterized by similar patterns of male-dependent carboxylesterase overexpression. The phenomenon of conserved carboxylesterase overexpression indicates similar male sex-associated functions of the enzymes. There is possible evidence of carboxylesterase recruitment by male reproductive-tract tissues indi-cating that it could be adaptive for spermatogenesis, sperm maturation and sperm use. Moreover, this idea can be extended to include a sperm cell lineage protection. This issue is discussed in the light of recent data on environmental reproductive xenobiotics that can provide a basis for a hypothetical explanation of car-boxylesterase overexpression in the male reproductive tract. Based on a well-known role of car-boxylesterases in detoxification of environmental chemicals such as organophosphate pesticides, it is proposed that various male genital tract carboxylesterases may be characterized by a similar physiological function to protect the male reproductive system against xenobiotic influences that could provoke its dys-function, thus altering sperm differentiation and maturation.

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ATP secretion in the male reproductive tract: essential role of CFTR

The Journal of Physiology ◽

10.1113/jphysiol.2012.230581 ◽

2012 ◽

Vol 590 (17) ◽

pp. 4209-4222 ◽

Cited By ~ 29

Author(s):

Ye Chun Ruan ◽

Winnie W. C. Shum ◽

Clémence Belleannée ◽

Nicolas Da Silva ◽

Sylvie Breton

Keyword(s):

Essential Role ◽

Reproductive Tract ◽

Male Reproductive Tract ◽

Atp Secretion

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Estrogen Modulates Glycerol Permeability in Sertoli Cells through Downregulation of Aquaporin-9

Cells ◽

10.3390/cells7100153 ◽

2018 ◽

Vol 7 (10) ◽

pp. 153 ◽

Cited By ~ 9

Author(s):

Raquel Bernardino ◽

David Carrageta ◽

Ana Silva ◽

Giuseppe Calamita ◽

Marco Alves ◽

...

Keyword(s):

Sertoli Cells ◽

Reproductive Tract ◽

Fluid Secretion ◽

Male Reproductive Tract ◽

Aquaporin 9 ◽

Important Regulator ◽

17Β Estradiol ◽

And Function ◽

Glycerol Permeability

High 17β-Estradiol (E2) levels are known to cause alterations of spermatogenesis and environments throughout the male reproductive tract. Sertoli cells (SCs) ensure an adequate environment inside the seminiferous tubule. Glycerol stands as essential for the maintenance of blood–testis barrier created by SCs, however, the role of E2 in this process is not known. Herein, we hypothesized that the effect of E2 on glycerol permeability in mouse SCs (mSCs) could be mediated by aquaglyceroporins. The expression of aquaglyceroporins was assessed by RT-PCR and qRT-PCR. Glycerol permeability was evaluated by stopped-flow light scattering. We were able to identify the expression of AQP3 and AQP9 in mSCs where AQP9 is more abundant than AQP3. Our results show that high E2 levels decrease AQP9 mRNA abundance with no influence on AQP3 in mSCs. Interestingly, high E2 levels decreased mSCs’ permeability to glycerol, while downregulating AQP9 expression, thus suggesting a novel mechanism by which E2 modulates fluid secretion in the testis. In conclusion, E2 is an important regulator of mSCs physiology and secretion through changes in AQP9 expression and function. Thus, alterations in glycerol permeability induced by E2 may be the cause for male infertility in cases associated with the presence of high E2 levels.

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Changes in distribution of labile zinc in mouse spermatozoa during maturation in the epididymis assessed by the fluorophore Zinquin

Reproduction Fertility and Development ◽

10.1071/rd9961097 ◽

1996 ◽

Vol 8 (7) ◽

pp. 1097 ◽

Cited By ~ 41

Author(s):

PD Zalewski ◽

X Jian ◽

LL Soon ◽

WG Breed ◽

RF Seamark ◽

...

Keyword(s):

Sodium Dodecyl Sulfate ◽

Reproductive Tract ◽

Regional Distribution ◽

Sodium Dodecyl ◽

Sperm Head ◽

Male Reproductive Tract ◽

Intracellular Location ◽

And Function ◽

Triton X

The Zn(II)-specific fluorophore Zinquin was used to determine the regional distribution of free or loosely-bound Zn(II) in mouse spermatozoa. Spermatozoa from the testes exhibited bright fluorescence over the entire head; those from the caput epididymides generally fluoresced more brightly in the post-acrosomal region; and spermatozoa from the caudae epididymides fluoresced less brightly, with foci of fluorescence over the sperm head which were lost after extraction with Triton X-100 and hence appeared to be membrane-associated. Treatment of cauda sperm with sodium dodecyl sulfate resulted in a bright uniform Zinquin fluorescence in the heads, similar to that observed in caput sperm, indicating that the two types of sperm have similar amounts of head Zn(II) but that the availability of Zn(II) for binding Zinquin is different. By contrast, the intensity of tail fluorescence was similar in spermatozoa from different regions of the male reproductive tract and was largely unaffected by Triton X-100 extraction, consistent with an intracellular location. Similar differences were observed between caput sperm and cauda sperm in the rat. It is concluded that visualization and measurement of free or loosely-bound Zn(II) in subcellular compartments of spermatozoa should facilitate investigation of the role of this metal in the development and function of spermatozoa and abnormalities that might accompany infertility and Zn(II) deficiency.

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Role of exosomes in sperm maturation during the transit along the male reproductive tract

Blood Cells Molecules and Diseases ◽

10.1016/j.bcmd.2005.03.005 ◽

2005 ◽

Vol 35 (1) ◽

pp. 1-10 ◽

Cited By ~ 171

Author(s):

Robert Sullivan ◽

Fabrice Saez ◽

Julie Girouard ◽

Gilles Frenette

Keyword(s):

Reproductive Tract ◽

Sperm Maturation ◽

Male Reproductive Tract

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The Transformative Impact of Extracellular Vesicles on Developing Sperm

Reproduction and Fertility ◽

10.1530/raf-20-0076 ◽

2021 ◽

Author(s):

Michael P Rimmer ◽

Christopher D Gregory ◽

Rod T Mitchell

Keyword(s):

Extracellular Vesicles ◽

Acrosome Reaction ◽

Reproductive Tract ◽

Seminiferous Tubules ◽

Parent Cell ◽

Male Reproductive Tract ◽

Future Fertility ◽

Cell Niche ◽

Transformative Impact

Objective To review the role of extracellular vesicles (EVs) released from the male reproductive tract and their impact on developing sperm. We discuss how sperm exiting the seminiferous tubules, although developmentally mature, require further modification. Acquisition of various functions including increased motility, transfer of cargoes and ability to undertake the acrosome reaction are mediated through the interaction between sperm and EVs. Methods A review of the literature identified that EVs are released from different portions of the male reproductive tract, notably the epididymis and prostate. These EVs interact with sperm as they pass from the seminiferous tubules to the epididymis and vas deferens prior to ejaculation. Results EVs are small lipid bound particles carrying bespoke RNA, protein and lipid cargoes. These cargoes are loaded based on the state of the parent cell and are used to communicate with recipient cells. In sperm, these cargoes are essential for post testicular modification. Sperm extracted from the proximal epididymis are poorly motile and unable to carry out the acrosome reaction. Conclusions Interaction between developing sperm and EVs is important for the subsequent function of sperm. Little is known however about EVs released from the seminiferous tubules to developing sperm or in the fetal and pre-pubertal testes. A greater understanding, especially in the formation and development of the spermatogonial stem cell niche may lead to new insights as to how damage to this niche may be prevented and preserve future fertility.

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