Leveraging menstrual effluent (ME) to investigate vitamin D and human decidualization, a potential link with fertility

  • J Clin Endocrinol Metab. 2026 Jan 5:dgaf708. doi: 10.1210/clinem/dgaf708.
Christine N Metz  1  2 ,  Prodyot K Chatterjee  1 ,  Nathaniel Hyman  1 ,  Stephanie Busch  1  2 ,  Sophia A Tarasenko  1 ,  Andrew N Hoofnagle  3 ,  Peter K Gregersen  1  2 ,  Anne Z Steiner  4 ,  Anne Marie Z Jukic  5
Affiliations
  • 1. Northwell, Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA.
  • 2. Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549.
  • 3. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195, USA.
  • 4. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
  • 5. Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC 27709, USA.
PMID: 41492807 DOI: 10.1210/clinem/dgaf708
Abstract

Context: Low vitamin D levels have been associated with female infertility, but the underlying mechanisms are not understood.

Objectives: To examine vitamin D treatment, in vitro and in vivo, on human endometrial stromal cell (eSC) decidualization, including mediating pathways. To assess feasibility of vitamin D measurement in menstrual effluent (ME).

Design: ME, ME-eSCs, and peripheral plasma were collected from participants in the Research Outsmarts Endometriosis (ROSE) study (2017-2024) and the Investigation of Vitamin D and Menstrual Cycles trial (inVitD) (2022-2024; NCT05050916).

Setting: ROSE study: North America; inVitD study: Detroit, MI and Durham, NC.

Participants: Healthy females aged 19-40 years. The inVitD trial participants provided ME pre- and post-cholecalciferol supplementation.

Intervention: Oral cholecalciferol supplementation (50,000 IU/week or 4,200 IU/week x 3 months) was provided to vitamin D deficient inVitD trial participants.

Main outcome measure: First, we examined the effect of active vitamin D (calcitriol) on ME-eSC decidualization in vitro. Second, we compared ME-eSC decidualization pre- and post-oral cholecalciferol supplementation. Mechanistic studies investigated target signaling proteins and mRNA expression. Third, we compared levels of vitamin D biomarkers in peripheral plasma versus ME.

Results: Calcitriol increased eSC decidualization measured by IGFBP1 (p<0.0001) and Prolactin levels (p<0.0001). Calcitriol and decidualization alone induced VDR mRNA expression. Calcitriol reduced Akt and PRAS40 phosphorylation during decidualization. Decidualization capacity increased following in vivo cholecalciferol supplementation (p=0.07). Peripheral plasma 1,25(OH)2D levels were correlated with ME levels (r=0.66, p=0.01).

Conclusions: Vitamin D enhances eSC decidualization, likely through reduced Akt signaling and downstream events, highlighting its potential role in fertility. Vitamin D biomarkers were measurable in ME.

Keywords
calcitriol; endometrium; fertility; implantation; pregnancy; progesterone; vitamin D supplementation.
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