Unveiling myometrial SP/Krüppel-like factors as drivers of parturition: insights from transcriptional and endocrine regulatory networks.

Graphical abstract: Abstract: Parturition is a complex process that is subject to multifactorial regulation by signals originating from the fetus, placenta, and uterus. The uterine myometrium is a central player for achieving successful pregnancy to term, requiring its transformation from a quiescent and growing entity to one of significant contractility within a narrow window of intricately regulated events. Receptors for the steroid hormones progesterone and estrogen are critical to myometrial transformative processes. Specificity protein/Krüppel-like factor (SP/KLF) family members are transcriptional regulators that play key roles in human physiology and pathology, in part as members of steroid hormone signaling networks. Here we review findings to establish the molecular rationale for a novel function of multiple SP/KLF proteins in human parturition. Support for their potential crucial roles includes: i) differential levels of myometrial expression at labor; ii) transcriptional regulation of myometrial expressed genes; iii) functional abilities to mechanistically influence steroid hormone signaling; and iv) parturition-associated hormonal control of their expression. Understanding myometrial SP/KLF networks in the physiologic control of myometrial contractility may have therapeutic relevance for management of aberrant labor onset to reduce maternal and neonatal morbidity and mortality.