Non-hormonal Male Contraceptives Research Articles

In Vitro Versus In Vivo Effects of NB-DGJ and NB-DNJ as Lead Compounds for Development of Non-Hormonal Reversible Oral Male Contraceptives.

In Vitro Versus In Vivo Effects of NB-DGJ and NB-DNJ as Lead Compounds for Development of Non-Hormonal Reversible Oral Male Contraceptives.

Approaches to the identification of new nonhormonal targets for male contraception

Fertility control is a global health issue with major personal and societal impact. Although, currently, there are several different options for contraception, the technologies behind these are antiquated, and the options for male-based contraception (i.e., withdrawal, condom and vasectomy) are inadequate. The genomic, proteomic and bioinformatic revolutions have provided new tools and new targets for contraceptive development, and the results of such approaches have identified gene products that play critical roles in male reproduction, thus expanding the array of potential targets for novel and innovative male-based contraceptives. This article will review the types of targets being considered in the development of nonhormonal male contraceptives and the technologies used to identify and validate these targets.

Exploiting the Potential of Iminosugars as Novel Reversible Non-Hormonal Male Contraceptive.

Exploiting the Potential of Iminosugars as Novel Reversible Non-Hormonal Male Contraceptive.

Delivery of Contraceptives to Men: Lesson from Other Therapeutic Drugs

Besides hormonal-based male contraceptives, such as testosterone undecanoate (a long-chain ester of testosterone) which can be administered either orally as contraceptive pill or by injection, some efforts have been made in the field to develop non-hormonal contraceptives to suppress spermatogenesis. One of the major goals for non-hormonal contraceptives is to avoid a disruption of the hypothalamic- pituitary-testicular axis, without affecting the systemic testosterone, LH and FSH levels, hoping to minimize the side-effects since testosterone has multiple target organs besides the testis. However, these non-hormonal male contraceptives are often met with poor absorption at the gastrointestinal tract and if they are peptide/protein based, they are subjected to proteolytic cleavage following oral administration. Thus, other non-oral routes are being considered. In this short review, we highlighted some of the latest development in the field regarding the administration of other therapeutic drugs via non-parenteral and non-oral routes. This information as briefly reviewed herein should provide some insights for delivery of male contraceptives in the future. Keywords: Male contraception, drug delivery, blood-testis barrier, testis, nasal drug delivery, transdermal drug delivery

Identification of Testis‐Specific Male Contraceptive Targets

In an effort to identify novel targets for the development of nonhormonal male contraceptives, genome-wide transcriptional profiling of the rat testis was performed. Specifically, enzymatically purified spermatogonia plus early spermatocyctes, pachytene spermatocytes, round spermatids, and Sertoli cells was analyzed along with microdissected rat seminiferous tubules at stages I, II-III, IV-V, VI, VIIa,b, VIIc,d, VIII, IX- XI, XII, XIII-XIV of the cycle of the seminiferous epithelium using RAE 230_2.0 microarrays. The combined analysis of these studies identified 16,971 expressed probe sets on the array. How these expression data, combined with additional bioinformatic data analysis and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis, led to the identification of 58 genes that have 1000-fold higher expression transcriptionally in the testis when compared to over 20 other nonreproductive tissues is described. The products of these genes may play important roles in testicular and/or sperm function, and further investigation on their utility as nonhormonal contraceptive targets is warranted. Moreover, these microarray data have been used to expedite the identification of a mutation in RIKEN cDNA 2410004F06 gene as likely being responsible for spermatogenic failure in a line of infertile mice generated by N-ethyl-N-nitrosourea (ENU) mutagenesis. The microarray data and the qRT-PCR data described are available in the Mammalian Reproductive Genetics database (http://mrg.genetics.washington.edu/).

Alkylated Imino Sugars, Reversible Male Infertility-Inducing Agents, Do Not Affect the Genetic Integrity of Male Mouse Germ Cells During Short-Term Treatment Despite Induction of Sperm Deformities1

Reversible infertility can be induced in male mice by oral administration of the alkylated imino sugars N-butyldeoxynojirimycin (NB-DNJ) and N-butyldeoxygalactonojirimycin (NB-DGJ). Spermatozoa of these mice have grossly misshapen heads and reduced motility. Because NB-DNJ and related compounds may hold promise as nonhormonal male contraceptives, a comprehensive examination of their effects on male reproduction is necessary. To this end, we further examined reproductive properties of the dysmorphic spermatozoa that are produced after short-term imino sugar administration at the minimal dose that completely abolishes the ability of male C57BL/6 mice to produce offspring by natural mating. Here, we report that, in vitro, the abnormal spermatozoa from the NB-DNJ- and NB-DGJ-treated mice were unable to fertilize oocytes. In addition, we investigated whether the imino sugars damage the genetic integrity of spermatozoa. To test this, we microsurgically injected deformed spermatozoa from imino sugar-treated males into oocytes. The deformed spermatozoa from the testis were able to activate oocytes very efficiently, but those from the cauda epididymis often failed to do so. This problem was overcome when the sperm-injected oocytes were treated with a parthenogenetic agent, Sr(2+). Oocytes injected with the misshapen spermatozoa from NB-DNJ- and NB-DGJ-treated mice developed (with or without Sr(2+) treatment) into live offspring that grew normally and were normally fertile. This indicates that during short-term administration, alkylated imino sugars alter sperm morphology and physiology but do not diminish the genetic potential of spermatozoa.