Inhibition of the acrosome reaction (AR) and fertilization capacity of mouse spermatozoa by norethisterone A-ring reduced metabolite (5alpha-NET)

Abstract

The contra gestational effects of norethisterone and its main metabolites, 5alpha-NET and 3beta5alpha-NET, has been demonstrated in several species. However, the focus has been mainly on their effects in the uterus. We previously reported that 5alpha-NET inhibits the progesterone-induced AR in pig spermatozoa and induces severe morphological damage to fertilized mouse oocytes. In the present study, we analysed the effects of these compounds on the fertilization process in vitro. Oocytes and spermatozoa were obtained from Balb/c female and C57BL/6J male mice, respectively. Both, the AR assays and the fertilization experiments were performed under different steroid treatment schemes using progesterone as a control. Results showed that norethisterone induced the AR, while 5alpha-NET reduced the percentage of spermatozoa that had undergone progesterone-induced AR. Both 17beta-estradiol and 3beta5alpha-NET induced the AR in a considerably lower percentage of spermatozoa than progesterone. In addition, when 5alpha-NET was added to the medium simultaneously with progesterone at the moment of fertilization, the percentage of fertilized oocytes (two-cell stage) decreased by as much as 77% as compared with the control progesterone-treated group. All results suggest that these compounds can have important effects on the fertilization process.

Progesterone Accelerates the Completion of Sperm Capacitation and Activates CatSper Channel in Spermatozoa from the Rhesus Macaque1

“…In short, our data suggest that macaque sperm under the conditions described here are uniquely sensitive to the priming effects of this steroid hormone. Further supporting the species differences in AR requirements, we note that capacitated mouse sperm readily complete the AR in response to progesterone [45] and that, in transgenic male mice whose spermatozoa express enhanced green fluorescence protein, the vast majority of sperm can be seen to undergo the AR as they transit through the cumulus and before binding to the ZP [46]. Similarly, in humans, progesterone has been shown to directly induce both capacitation and the AR [14].…”

Dose-response effects of estrogenic mycotoxins (zearalenone, alpha- and beta-zearalenol) on motility, hyperactivation and the acrosome reaction of stallion sperm

“…The currently favored theory is that E 2 inhibits the progesterone- or ATP-induced AR in both human [23,42,43] and bovine [44] sperm. However, studies in the mouse have documented a stimulatory effect of E 2 on the AR [45,46]. On the other hand, it may be significant that different incubation conditions (medium, time), staining (FITC-PNA or FITC-Pisum sativum agglutinin – PSA) and evaluation techniques (fluorescence microscope or flow cytometry) were used in the various studies.…”