Journal ArticleDOI
Progesterone activates the principal Ca2+ channel of human sperm.
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TLDR
It is found that nanomolar concentrations of progesterone dramatically potentiate CatSper, a pH-dependent Ca2+ channel of the sperm flagellum, which represents a promising target for the development of a new class of non-hormonal contraceptives.Abstract:
Steroid hormone progesterone released by cumulus cells surrounding the egg is a potent stimulator of human spermatozoa. It attracts spermatozoa towards the egg and helps them penetrate the egg's protective vestments. Progesterone induces Ca(2+) influx into spermatozoa and triggers multiple Ca(2+)-dependent physiological responses essential for successful fertilization, such as sperm hyperactivation, acrosome reaction and chemotaxis towards the egg. As an ovarian hormone, progesterone acts by regulating gene expression through a well-characterized progesterone nuclear receptor. However, the effect of progesterone upon transcriptionally silent spermatozoa remains unexplained and is believed to be mediated by a specialized, non-genomic membrane progesterone receptor. The identity of this non-genomic progesterone receptor and the mechanism by which it causes Ca(2+) entry remain fundamental unresolved questions in human reproduction. Here we elucidate the mechanism of the non-genomic action of progesterone on human spermatozoa by identifying the Ca(2+) channel activated by progesterone. By applying the patch-clamp technique to mature human spermatozoa, we found that nanomolar concentrations of progesterone dramatically potentiate CatSper, a pH-dependent Ca(2+) channel of the sperm flagellum. We demonstrate that human CatSper is synergistically activated by elevation of intracellular pH and extracellular progesterone. Interestingly, human CatSper can be further potentiated by prostaglandins, but apparently through a binding site other than that of progesterone. Because our experimental conditions did not support second messenger signalling, CatSper or a directly associated protein serves as the elusive non-genomic progesterone receptor of sperm. Given that the CatSper-associated progesterone receptor is sperm specific and structurally different from the genomic progesterone receptor, it represents a promising target for the development of a new class of non-hormonal contraceptives.read more
Citations
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Journal ArticleDOI
Nanomaterials enhanced surface plasmon resonance for biological and chemical sensing applications
TL;DR: The latest trend and challenges in engineering and applications of nanomaterials-enhanced surface plasmon resonance sensors for detecting "hard-to-identify" biological and chemical analytes are reviewed and discussed.
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Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility
Niels E. Skakkebæk,Ewa Rajpert-De Meyts,Germaine M. Buck Louis,Jorma Toppari,Anna-Maria Andersson,Michael L. Eisenberg,Tina Kold Jensen,Niels Jørgensen,Shanna H. Swan,Katherine J. Sapra,Søren Ziebe,Lærke Priskorn,Anders Juul +12 more
TL;DR: There is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations, because environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends.
Journal ArticleDOI
The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm
Timo Strünker,Normann Goodwin,Christoph Brenker,Nachiket D. Kashikar,Nachiket D. Kashikar,Ingo Weyand,Reinhard Seifert,U. Benjamin Kaupp +7 more
TL;DR: It is found that both progesterone and alkaline pH stimulate a rapid Ca2+ influx with almost no latency, incompatible with a signalling pathway involving metabotropic receptors and second messengers.
Journal ArticleDOI
Calcium Channels in the Development, Maturation, and Function of Spermatozoa
TL;DR: This review critically examines the involvement of Ca(2+) channels in multiple signaling processes needed for spermatozoa to mature, travel towards the egg, and fertilize it.
Journal ArticleDOI
The control of male fertility by spermatozoan ion channels.
TL;DR: How ion channels regulate sperm physiology is discussed, including mutations and deletions in sperm-specific ion channels affect male fertility in both mice and humans without affecting other physiological functions.
References
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Journal ArticleDOI
The steroid and thyroid hormone receptor superfamily
TL;DR: A superfamily of regulatory proteins that include receptors for thyroid hormone and the vertebrate morphogen retinoic acid is identified, suggesting mechanisms underlying morphogenesis and homeostasis may be more ubiquitous than previously expected.
Journal ArticleDOI
Nongenomic actions of steroid hormones
Ralf Lösel,Martin Wehling +1 more
TL;DR: This work has identified other responses to steroids that are much more rapid and take place in seconds or minutes, and they are not rare.
Journal ArticleDOI
A sperm ion channel required for sperm motility and male fertility
Dejian Ren,Betsy Navarro,Gloria I. Perez,Alexander C. Jackson,Shyue-Fang Hsu,Qing Shi,Jonathan L. Tilly,David E. Clapham +7 more
TL;DR: A putative sperm cation channel, CatSper, whose amino-acid sequence most closely resembles a single, six-transmembrane-spanning repeat of the voltage-dependent Ca2+-channel four-repeat structure is described, located specifically in the principal piece of the sperm tail.
Journal ArticleDOI
The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm
Timo Strünker,Normann Goodwin,Christoph Brenker,Nachiket D. Kashikar,Nachiket D. Kashikar,Ingo Weyand,Reinhard Seifert,U. Benjamin Kaupp +7 more
TL;DR: It is found that both progesterone and alkaline pH stimulate a rapid Ca2+ influx with almost no latency, incompatible with a signalling pathway involving metabotropic receptors and second messengers.
Journal ArticleDOI
Contragestion and other clinical applications of RU 486, an antiprogesterone at the receptor
TL;DR: RU 486, a steroid with high affinity for the progesterone receptor, is the first available active antiprogesterone, and it has been used successfully as a medical alternative for early pregnancy interruption.