male contraceptive
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2022 ◽  
Author(s):  
Maxwell Claef Hakun ◽  
Janet Rossant ◽  
Bin Gu

Spermiogenesis, the post-meiotic stage of sperm development, is critical for normal male fertility. Many genetic defects and environmental assaults that affect spermiogenesis have been shown to be associated with male infertility. In addition, this later stage of spermatogenesis has been proposed to be an ideal target for male contraceptive development. The mouse is a widely used model for studying the mechanisms of spermatogenesis and spermiogenesis. However, due to the complexity and the asynchronous nature of spermatogenesis in adult testis, it is challenging to study molecular processes restricted to this specific developmental stage. It is also challenging to monitor the spermiogenesic activity in live mice, which is critical for screening for fertility-modulating interventions such as contraceptives. Here we reported the development of a Nutm1-T2A- luciferase 2(Luc2)-tandem Tomato(TdTomato) knock-in reporter mouse model that specifically labels post-meiotic spermatids. Homozygous reporter mice are healthy and fully fertile, demonstrating no interference with the normal functions of the Nutm1 gene by the reporter. We demonstrated the visualization of post-meiotic spermatids by fluorescent imaging of the TdTomato reporter in both live and fixed testis tissues. We also demonstrated bioluminescence imaging of Nutm1 expressing cells in live mice. The Nutm1-T2A-Luc2TdTomato reporter mouse can serve as a valuable tool for studying spermiogenesis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sheng Gao ◽  
Xiaolong Wu ◽  
Lingling Wang ◽  
Tiao Bu ◽  
Adolfo Perrotta ◽  
...  

There is emerging evidence that environmental toxicants, in particular endocrine disrupting chemicals (EDCs) such as cadmium and perfluorooctanesulfonate (PFOS), induce Sertoli cell and testis injury, thereby perturbing spermatogenesis in humans, rodents and also widelife. Recent studies have shown that cadmium (e.g., cadmium chloride, CdCl2) and PFOS exert their disruptive effects through putative signaling proteins and signaling cascade similar to other pharmaceuticals, such as the non-hormonal male contraceptive drug adjudin. More important, these signaling proteins were also shown to be involved in modulating testis function based on studies in rodents. Collectively, these findings suggest that toxicants are using similar mechanisms that used to support spermatogenesis under physiological conditions to perturb Sertoli and testis function. These observations are physiologically significant, since a manipulation on the expression of these signaling proteins can possibly be used to manage the toxicant-induced male reproductive dysfunction. In this review, we highlight some of these findings and critically evaluate the possibility of using this approach to manage toxicant-induced defects in spermatrogenesis based on recent studies in animal models.


Development ◽  
2021 ◽  
Author(s):  
Fang Yang ◽  
Maria Gracia Gervasi ◽  
N. Adrian Leu ◽  
Gerardo Orta ◽  
Darya A. Tourzani ◽  
...  

The CatSper cation channel is essential for sperm capacitation and male fertility. The multi-subunit CatSper complexes form highly organized calcium signaling nanodomains on flagellar membranes. Here we report identification of an uncharacterized protein C2CD6 as a novel subunit of the CatSper complex. C2CD6 contains a calcium-dependent membrane targeting C2 domain. C2CD6 associates with the CatSper calcium-selective core forming subunits. Deficiency of C2CD6 depletes the CatSper nanodomains from the flagellum and results in male sterility. C2CD6-deficient sperm are defective in hyperactivation and fail to fertilize oocytes both in vitro and in vivo. CatSper currents are present but at a significantly lower level in C2CD6-deficient sperm. Transient treatments with either Ca2+ ionophore, starvation, or a combination of both restore the fertilization capacity of C2CD6-deficient sperm. C2CD6 interacts with EFCAB9, a pH-dependent calcium sensor in the CatSper complex. We postulate that C2CD6 facilitates incorporation of the CatSper complex into the flagellar plasma membrane and may function as a calcium sensor. The identification of C2CD6 may enable the long-sought reconstitution of the CatSper ion channel complex in a heterologous system for male contraceptive development.


Author(s):  
Murugananthkumar Raju ◽  
Raghuveer Kavarthapu ◽  
Rajakumar Anbazhagan ◽  
Sergio A. Hassan ◽  
Maria L. Dufau

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
J Perrin ◽  
J Tcherdukian ◽  
A Netter ◽  
E Lechevalier ◽  
F Bretelle ◽  
...  

Abstract Study question Among health professionals involved in contraceptive prescribing, what are the knowledge, professional attitudes and training on male contraceptive methods? Summary answer The health professionals involved in prescribing contraception are not sufficiently trained in male contraception and almost all of them want more. What is known already The most recent large-scale studies show that 70% of couple contraception is provided by women and that the majority of men and women would be willing to adopt male contraception as couple contraception. The medicalization of contraception places the medical profession at the forefront of the acceptability of and information regarding a contraceptive method. However, only one study have evaluated health professionals’ knowledge of the various methods of male contraception (MC), including male hormonal contraception (MHC) and male thermal contraception (MTC). Study design, size, duration Between April 2020 and June 2020, we carried out a descriptive prospective multicentre study in a medical population of 2243 prescribers of couple contraception in France. Participants/materials, setting, methods The participants were obstetrician-gynaecologists, medical gynaecologists, general practitioners or midwives. They completed a three-part numerical questionnaire, including i) sociodemographic characteristics and personal experiences with contraception, ii) knowledge and professional attitudes about male contraception and iii) training on male contraception. Main results and the role of chance The overall participation rate was 19% (340/2243). Condoms and withdrawal were known by 98% and 89% of the population, respectively. Vasectomy was known by 75% of the population and significantly better known by obstetrician-gynaecologists than by medical gynaecologists and general practitioners (p = 0.026). Male hormonal contraception (MHC) and male thermal contraception (MTC) were known by 10% and 23% of the population, respectively, and were significantly better known by medical gynaecologists and general practitioners than by other specialties (p < 0.001). More than half (55%) of the population never or infrequently offered MC during a couple’s contraceptive request consultation. Female practitioners offered MC significantly more often than male practitioners (48% vs. 26%; p = 0.033). Only 14% of the population had ever participated in training on MC, 96% wished to be better trained on MC, and 86% expressed a willingness to participate in such a training. Limitations, reasons for caution The population was mainly representative of medical health practitioners of southeastern France. There was an over-representation of women in all medical specialties, except for midwives. Wider implications of the findings: Our study shows that health professionals involved in contraception have limited knowledge about MC and are eager to have more information about it. To advance the acceptability and dissemination of such contraceptive methods, it seems imperative to provide health professionals with an adapted training program on male contraception. Trial registration number 2020–01–23–03


2021 ◽  
pp. 1-3
Author(s):  
Kulvinder Kochar Kaur ◽  
Gautam Allahbadia ◽  
Mandeep Singh

In view of the world population escalating at an alarming rate anticipated population will reach 9.8 billion by 2050. In contrast to female contraceptive measures male contraceptive methods are relatively negligible. Maximum researchers have concentrated on generation of male contraceptive methods by trying to modulate hormones but had to abandon this strategy as the pharmaceutical companies were not happy in view of marked adverse actions. Maximum nonhormonal strategies in research concentrate on spermatogenesis repression or reversible physical barriers. Sperm motility represents one of the maximum significant markers of semen quality as it is necessary for sperm motion appropriately in the female reproductive tract for it to arrive intricately towards the egg as well as fertilize it. The group of Vijayraghavan S, et al. have been concentrating on generation of a male contraceptive by utilization of targeting sperm motility at epididymal level by extensively studying the regulation of flaggelar protein motion by various subunits like Protein Phosphatase 1 (PP1), Protein Phosphatase Inhibitor-2 (PPPIR2), its phosphorylation by Glycogen Synthase Kinase-3 (GSK3), A kinase anchor protein 4(AKAP4). Recently they attempted to generate a bioportide that could simulate binding of the anchor protein AKAP4 that had been earlier revealed as a PPγ2 interactor in human sperm,that are implicated in sperm motility .Unfortunately that did not abolish sperm motility completely .This seemed to be surprising as PP1/ PPPIR2crosstalk seems to be central in regulation of sperm motility. Thus Silva et al., pointed that evaluation of the probable part of PPPIR7 as well as PPPIR11 in the manipulation of sperm motility in men might be the aim of future studies that needs to be continued to get more insight in this field.


2021 ◽  
Vol 4 (1) ◽  
pp. 85-95
Author(s):  
Indri Indriyani ◽  
Hendri Busman ◽  
Sutyarso Sutyarso

The lack of participation of men in family planning programs is due to the limited choice of male contraceptive. Traditional medicinal plants are one of ideal alternative types of male contraception. This study aimed to study the effect of Cyperus rotundus L. rhizome on the quality and quantity of spermatozoa in male mice (Mus musculus L.). Twenty male mice were divided into four treatment groups, namely control group (C0), the dose of teki grass rhizome extract 4.5 mg/40 g BW (C1), the dose of teki grass rhizome extract 45 mg/40 g BW (C2), and the dose of teki grass rhizome extract 135 mg/40 g BW (C3) for 35 days. Parameters measured were the motility, viability, morphology, and concentration of spermatozoa. The data were analyzed for diversity and then further tested using the LSD test with a 5% significance level. The results of the analysis showed that giving teki grass rhizome extract had a significant effect on the motility, viability, morphology, and concentration of spermatozoa. It can be concluded that teki grass rhizome can be used as an alternative male contraception because it can reduce motility, viability, morphology, and spermatozoa concentration.


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