Vitamin D, the placenta and early pregnancy: effects on trophoblast function

Abstract

Pregnancy is associated with significant changes in vitamin D metabolism, notably increased maternal serum levels of active vitamin D, 1,25-dihydroxyvitamin (1,25(OH) 2 D). This appears to be due primarily to increased renal activity of the enzyme 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) that catalyzes synthesis of 1,25(OH) 2 D, but CYP27B1 expression is also prominent in both the maternal decidua and fetal trophoblast components of the placenta. The precise function of placental synthesis of 1,25(OH) 2 D remains unclear, but is likely to involve localized tissue-specific responses with both decidua and trophoblast also expressing the vitamin D receptor (VDR) for 1,25(OH) 2 D. We have previously described immunomodulatory responses to 1,25(OH) 2 D by diverse populations of VDR-expressing cells within the decidua. The aim of the current review is to detail the role of vitamin D in pregnancy from a trophoblast perspective, with particular emphasis on the potential role of 1,25(OH) 2 D as a regulator of trophoblast invasion in early pregnancy. Vitamin D deficiency is common in pregnant women, and a wide range of studies have linked low vitamin D status to adverse events in pregnancy. To date, most of these studies have focused on adverse events later in pregnancy, but the current review will explore the potential impact of vitamin D on early pregnancy, and how this may influence implantation and miscarriage.

Potential impact of maternal vitamin D status on peripheral blood and endometrium cellular immunity in women with recurrent implantation failure

“…In fact, our previous data suggested that vitamin D therapy for patients with a history of recurrent miscarriage improved immune abnormality with insufficient or deficient vitamin D status, resulting in a prevention of pregnancy loss 6 . In light of this, it has been speculated that vitamin D could act as an immune regulator during implantation and play an important role in reproductive capacity 37,38 …”

Maternal vitamin D deficiency and developmental origins of health and disease (DOHaD)

“…Findings from a recent human study provide evidence that the placenta, working as the interface between mother and fetus, modulates circulating vitamin D metabolites in pregnant women and that it favors the uptake of DBP-bound 25(OH)D3 through a specific receptor system (LRP2-CUBN) (Park et al 2017). In the placenta, CYP27B1 activity is detectable in both maternal decidua and fetal trophoblast, which then allows for local production of 1,25(OH) 2 D from maternal 25(OH)D via 1-alpha-hydroxylase (Ganguly et al 2018). Likewise, both decidua and trophoblast also express VDR (Liu & Hewison 2012).…”

“…Placental production of 1,25(OH) 2 D is proposed to be essential for immunosuppressive effects required for immune tolerance of implantation. However, ex vivo and in vitro studies provide evidence for a more extensive role of vitamin D in placental function, including trophoblastic differentiation and extravillous trophoblast invasion of the decidua and myometrium (Ganguly et al 2018).…”

Effects of micronutrients on placental function: evidence from clinical studies to animal models

“…Vitamin D may be beneficial during the establishment of pregnancy, by promoting an immunologically tolerant environment in the decidua and regulating a R73 www.reproduction-online.org Reproduction (2018) 156 R69-R82 number of genes critical for implantation, e.g. CABP9K and HOXA10 (reviewed elsewhere Evans et al 2004, Ganguly et al 2018. Vitamin D also promotes EVT invasion in vitro (Chan et al 2015) and can modulate the inhibitory effects of locally active lipid metabolite sphingosine-1-phosphate (S1P) on EVT migration (Hay et al 2016).…”