A review: alteration of in vitro reproduction processes by thiols —Emphasis on 2-mercaptoethanol

Abstract

Descriptions of organosulfurs altering biologically relevant cellular functions began some 40 years ago when murine in vitro cell mediated and humoral immune responses were shown to be dramatically enhanced by any of four xenobiotic, sulfhydryl compounds—2-mercaptoethanol (2ME), dithiothreitol (DTT), glutathione, and L-cysteine; the most effective were 2ME and DTT. These findings triggered a plethora of reports defining 2ME benefits for a multitude of immunological processes. This in turn led to investigations on 2ME alterations of (a) immune functions in other species, (b) activities of other cell-types, and (c) in vivo diseases. In addition, these early findings preceded the identification of previously undefined anticarcinogenic chemicals in specific foods as organosulfurs. Taken all together, there is little doubt that organosulfur compounds have enormous benefits for cellular functions and for a multitude of diseases. Issues of importance still to be resolved are (a) clarification of mechanisms that underlie alteration of in vitro and in vivo processes and perhaps more importantly, (b) which if any in vitro alterations are relevant for (i) alteration of in vivo diseases and (ii) identification of other diseases that might therapeutically benefit from organosulfurs. As one means to address these questions, reviews of different processes impacted by thiols could be informative. Therefore, the present review on alterations of in vitro fertilization processes by thiols (mainly 2ME, since cysteamine alterations have been reviewed) was undertaken. Alterations found to occur in medium supplemented with 2ME were enhancement, no effect, or inhibition. Parameters associated with which are discussed as they relate to postulated thiol mechanisms.

Thiosulfoxide (Sulfane) Sulfur: New Chemistry and New Regulatory Roles in Biology

“…Aside from their absolute requirement in the MTAP- and CTH-defective cells, these precursors of sulfane sulfur have dramatic effects in increasing the viability, health, vigor, and proliferative capacity of many cell types in vitro . Today, MER, TGL, or TEA are routinely added to many in vitro cell systems involving immune cells, hematopoietic cells, reproductive cells, embryonic cells, and stem cells [ 29 , 30 , 31 ]. These sulfane precursor compounds are added at μM concentrations and, by integration of kinetic parameters, it can be shown that the concentration of sulfane sulfur in the media at any time is in the nanomolar (nM) range [ 17 ].…”

“…The fact that these sulfane chains are present in the “H 2 S” test systems supports the conclusion that the active agent is sulfane sulfur rather than hydrogen sulfide. It should be noted that the proposed agents (thiophosphates and dithiolethiones) are less appropriate as “therapeutic” agents than are mercaptoethanol disulfide and cystamine, which have already been tested in animals [ 29 , 30 , 31 ].…”

“…This increased vigor could indirectly increase the cellular content of oxygen-defensive factors such as glutathione, catalase, and superoxide dismutase. Numerous reports have described an increase in cellular glutathione in the presence of sulfur compounds related to sulfane sulfur [ 29 , 30 , 31 , 45 , 54 ]. The presence of air-exposed solutions of NaHS has been shown to increase the expression of Mn-SOD in ischemia-stressed cardiomyocytes as well as the in vitro activity of CuZn SOD [ 103 ].…”