Kisspeptin Is a Novel Regulator of Human Fetal Adrenocortical Development and Function: A Finding With Important Implications for the Human Fetoplacental Unit

Abstract

Context:The human fetal adrenal (HFA) is an integral component of the fetoplacental unit and important for the maintenance of pregnancy. Low kisspeptin levels during pregnancy are associated with miscarriage, and kisspeptin and its receptor are expressed in the HFA. However, the role of kisspeptin in fetal adrenal function remains unknown.Objective:To determine the role of kisspeptin in the developing HFA.Design:Experiments using H295R and primary HFA cells as in vitro models of the fetal adrenal. Association of plasma kisspeptin levels with HFA size in a longitudinal clinical study.Setting:Academic research center and tertiary fetal medicine unit.Participants:Thirty-three healthy pregnant women were recruited at their 12-week routine antenatal ultrasound scan.Main Outcome Measures:The spatiotemporal expression of Kiss1R in the HFA. The production of dehydroepiandrosterone sulfate (DHEAS) from HFA cells after kisspeptin treatment, alone or in combination with adrenocorticotropic hormone or corticotropin-releasing hormone. Fetal adrenal volume (FAV) and kisspeptin levels at four antenatal visits (∼20, 28, 34, and 38 weeks’ gestation).Results:Expression of Kiss1R was present in the HFA from 8 weeks after conception to term and was shown in the inner fetal zone. Kisspeptin significantly increased DHEAS production in H295R and second-trimester HFA cells. Serial measurements of kisspeptin confirmed a correlation with FAV growth in the second trimester, independent of sex or estimated fetal weight.Conclusions:Kisspeptin plays a key role in the regulation of the HFA and thus the fetoplacental unit, particularly in the second trimester of pregnancy.

The transient cortical zone in the adrenal gland: the mystery of the adrenal X-zone

“…Kisspeptin is expressed in all cortical zones including the inner fetal zone in human fetal adrenals (Katugampola et al 2017). Although Kiss1 and Kiss1 receptor (Kiss1r) KO mice have a persistent X-zone (Berthon et al 2018), the expression levels of Kiss1 and Kiss1r are very low in adrenals with or without an X-zone (preliminary RNAseq data from our laboratory).…”

Is There An Association Between Kisspeptin Levels And Gestational Diabetes Mellitus?

“…In the existing literature, there is a body of evidence showing that kisspeptin has important roles in regulating glucose homeostasis, insulin secretion, food intake and body composition. It is also known that inadequate kisspeptin signaling results in decreased locomotor activity and increased adiposity (18)(19)(20)(21).…”

Investigation of Kisspeptin Role in Experimental Kidney Ischemia/Reperfusion Injury

“…It has been reported that during the pregnancy period, the concentration of kisspeptin at the dramatic level increases, eventually increasing the level of aldosterone in the fetal adrenal gland. 23 It has also been reported that kisspeptin induces aldosterone secretion by increasing Ang II level. In our study, the decrease in serum kisspeptin levels in the I/R group was not significant, but serum Ang II and aldosterone levels were significantly decreased.…”