Gasotransmitters in Gametogenesis and Early Development: Holy Trinity for Assisted Reproductive Technology-A Review

Abstract

Creation of both gametes, sperm and oocyte, and their fusion during fertilization are essential step for beginning of life. Although molecular mechanisms regulating gametogenesis, fertilization, and early embryonic development are still subjected to intensive study, a lot of phenomena remain unclear. Based on our best knowledge and own results, we consider gasotransmitters to be essential for various signalisation in oocytes and embryos. In accordance with nitric oxide (NO) and hydrogen sulfide (H2S) physiological necessity, their involvement during oocyte maturation and regulative role in fertilization followed by embryonic development have been described. During these processes, NO- and H2S-derived posttranslational modifications represent the main mode of their regulative effect. While NO represent the most understood gasotransmitter and H2S is still intensively studied gasotransmitter, appreciation of carbon monoxide (CO) role in reproduction is still missing. Overall understanding of gasotransmitters including their interaction is promising for reproductive medicine and assisted reproductive technologies (ART), because these approaches contend with failure of in vitro assisted reproduction.

Figure 1

Gasotransmission in oocytes, resulting in S-sulfhydration and nitrosylation of various factors. Both gasotransmitters NO and H₂S are enzymatically released, respectively, from L-arginine and L-cysteine. Subsequently, NO- and/or H₂S-posttranslationally modified proteins lead to MPF/MAPK-orchestrated meiotic maturation reinitiation (equal to GVBD, germinal vesicle breakdown) and completion (with extruded polar body and small particles visible in perivitelline space). S-sulfhydration of MEK, upstream MAPK kinase, is known [61] and more S-sulfhydrated factors are considered. In addition to S-sulfhydration, S-nitrosylation seems to be exclusive mechanism of NO-regulated oocyte maturation [34]. Disclosure of complete “S-sulfhydration” and “S-nitrosylation” is still lacking (X-S-SH, X-S-NO) and we can assume wide protein index underwent this posttranslational modifications as well as NO-H₂S intraprotein cross-talking (HS-S-X-S-NO).

Figure 2

NO action in oocyte activation is evolutionary inconsistent. The NO/sCG/cGMP/PKG signal pathways are presumed, where dual NO effect on sCG, resulting in its S-nitrosylation and NO binding, is expectable. Obviously, dependency of fertilization and oocyte activation, followed by cleavage and the second polar bod extrusion, is shaded in evolutionary more developed organisms, where fulfilment of certain conditions (Ca²⁺ presence, pulsative character of NO) is necessary.