Brdt Bromodomains Inhibitors and Other Modern Means of Male Contraception

Zdrojewicz, Zygmunt; Konieczny, Radosław; Papier, Paulina; Szten, Filip

doi:10.17219/acem/33827

Cited by 9 publications

(5 citation statements)

References 35 publications

(62 reference statements)

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“…The studies conducted on male reproductive cells of mammals (man and mouse) showed that bromodomain inhibitor JQ1 blocked BRDT, and the effects of its activity depended on the time of application and its dose. JQ1 affected the developmental stages of these cells already during meiosis and successive post-meiotic stages [43,50]. In the studied alga, it was not possible to examine how JQ1 treatment affected meiosis, because Chara has a different type of meiosis (to plants and mammals), which occurs only after fertilization.…”

Section: Discussionmentioning

confidence: 99%

Blocking the Bromodomains Function Contributes to Disturbances in Alga Chara vulgaris Spermatids Differentiation

Wojtczak

2020

Cells

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Bromodomain containing (BRD) proteins play an essential role in many cellular processes. The aim of this study was to estimate activity of bromodomains during alga Chara vulgaris spermatids differentiation. The effect of a bromodomain inhibitor, JQ1 (100 μM), on the distribution of individual stages of spermatids and their ultrastructure was studied. The material was Feulgen stained and analysed in an electron microscope. JQ1 caused shortening of the early stages of spermiogenesis and a reverse reaction at the later stages. Additionally, in the same antheridium, spermatids at distant developmental stages were present. On the ultrastructural level, chromatin fibril system disorders and significantly distended endoplasmic reticulum (ER) cisternae already at the early stages were observed. Many autolytic vacuoles were also visible. The ultrastructural disturbances intensified after prolonged treatment with JQ1. The obtained data show that JQ1 treatment led to changes in the spermatid number and disturbances in chromatin condensation and to cytoplasm reduction. The current studies show some similarities between C. vulgaris and mammals spermiogenesis. Taken together, these results suggest that JQ1 interferes with the spermatid differentiation on many interdependent levels and seems to induce ER stress, which leads to spermatid degeneration. Studies on the role of bromodomains in algae spermiogenesis have not been conducted so far.

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Section: Discussionmentioning

confidence: 99%

Blocking the Bromodomains Function Contributes to Disturbances in Alga Chara vulgaris Spermatids Differentiation

Wojtczak

2020

Cells

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“…a spermiumok mozgását gátolhatja, amely segítségével a hím ivarsejtek progresszív motilitása megszüntethető, így a fogamzásgátló hatás elérhető [47]. Alternatív lehetőség a Sertoli-sejtek és a korai fázisban lévő spermium-előalakok közötti sejt-sejt kapcsolat megszakítása, amely a spermiogenezis blokádját jelenti.…”

Section: Egyéb Nem Hormonális Lehetőségekkitekintésunclassified

“…Alternatív lehetőség a Sertoli-sejtek és a korai fázisban lévő spermium-előalakok közötti sejt-sejt kapcsolat megszakítása, amely a spermiogenezis blokádját jelenti. Az erre alkalmas vegyületek (adjudin, gamendazol, CDB-4022) humán alkalmazása egyelőre vesekárosító hatásuk miatt nem kivitelezhető, de a jövőben a mellékhatásprofil optimalizálása mellett fogamzásgátlásra alkalmasak lehetnek [47].…”

Section: Egyéb Nem Hormonális Lehetőségekkitekintésunclassified

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Férfi hormonális fogamzásgátlás: múlt, jelen, jövő

et al. 2017

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In certain regions of the world the enormous rate of population growth raises economic and public health concerns and widely accessible contraceptive methods would be desired. In contrast, in other countries the use of effective contraception is a question of individual preferences. Today, most of the reliable contraceptive methods are applied by women, while the options for male methods are quite limited. It is well known that significant portion of pregnancies are still unplanned and several data revealed men's willingness to take part in family planning. Based on these needs, remarkable efforts have been made to develop a suitable hormonal contraceptive agent for men. With the exogenous suppression of follicle stimulating hormone and luteinizing hormone secretion, the inhibition of the testicular testosterone production and the spermatogenesis can be achieved. In the beginning, testosterone-derivatives, or testosterone-progestin combinations were administered, later synthetic androgen agents were developed. Despite of these efforts, unfortunately, there is no safe, widely feasible male hormonal contraception to date, but in the future this goal can be achieved by solving the key hurdles. Orv Hetil. 2017; 158(46): 1819-1830.

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“…These methods target a specific protein when inhibited by small molecules, or knocked out in mice will lead to infertility. Although these leads have enormous promise and preclinical studies are ongoing, clinical studies have not yet started (Tash et al, 2008;Chung et al, 2011;Matzuk et al, 2012;Paik et al, 2014;Zdrojewicz et al, 2015; O'Rand et al, 2016).…”

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confidence: 99%