Gasotransmitters are endogenous small gaseous messengers exemplified by
nitric oxide (NO),
carbon monoxide (CO), and
hydrogen sulfide (H2S or
sulfide).
Gasotransmitters are implicated in myriad physiologic functions including many aspects of reproduction. Our objective was to comprehensively review basic mechanisms and functions of
gasotransmitters during pregnancy from conception to uterine involution and highlight future research opportunities. We searched PubMed and Web of Science databases using combinations of keywords
nitric oxide,
carbon monoxide,
sulfide, placenta, uterus, labor, and pregnancy. We included English language publications on human and animal studies from any date through August 2018 and retained basic and translational articles with relevant original findings. All
gasotransmitters activate cGMP signaling. NO and
sulfide also covalently modify target
protein cysteines.
Protein kinases and
ion channels transduce
gasotransmitter signals, and co-expressed
gasotransmitters can be synergistic or antagonistic depending on cell type.
Gasotransmitters influence tubal transit, placentation, cervical remodeling, and myometrial contractility. NO, CO, and
sulfide dilate resistance vessels, suppress
inflammation, and relax myometrium to promote uterine quiescence and normal placentation. Cervical remodeling and
rupture of fetal membranes coincide with enhanced oxidation and altered
gasotransmitter metabolism. Mechanisms mediating cellular and organismal changes in pregnancy due to
gasotransmitters are largely unknown. Altered
gasotransmitter signaling has been reported for
preeclampsia,
intrauterine growth restriction, premature
rupture of membranes, and
preterm labor. However, in most cases specific molecular changes are not yet characterized. Nonclassical signaling pathways and the crosstalk among
gasotransmitters are emerging investigation topics.