Integrative Biomarkers in Female Reproductive Pathology: A Comparative Review of Vitamin D Signaling, Iron Homeostasis, and Kisspeptin Modulation

Abstract

Background: Female reproductive health is governed by a complex interplay between metabolic nutritional status and neuroendocrine regulation. Vitamin D deficiency and Iron Deficiency Anemia (IDA) are prevalent comorbidities in pregnancy, while Kisspeptin (KISS1) has emerged as a critical regulator of the Hypothalamic-Pituitary-Gonadal (HPG) axis and a metastasis suppressor in gynecological pathologies.

Objective: This review aims to synthesize current evidence linking Vitamin D deficiency to gestational anemia and to evaluate the diagnostic potential of Kisspeptin in endometriosis and reproductive cancers.

Methods: A comprehensive review of literature from 2000–2024 was conducted, focusing on observational studies, clinical trials, and molecular pathway analyses. Data regarding 25(OH)D levels, hemoglobin status, and KISS1 expression in endometrial tissues were analyzed.

Results: Vitamin D deficiency is significantly associated with increased risk of IDA in pregnant women, influencing neonatal outcomes such as APGAR scores. Mechanistically, Vitamin D modulates hepcidin, facilitating iron absorption. Conversely, aberrant Kisspeptin signaling is implicated in endometriosis via the PI3K/AKT/mTOR pathway and serves as a biomarker for ovarian carcinoma metastasis.

Conclusion: Nutritional and neurohormonal markers offer distinct but complementary insights into reproductive pathology. Integrating Vitamin D screening with novel biomarkers like Kisspeptin could enhance risk stratification for conditions ranging from gestational anemia to endometrial malignancies.

Keywords:

Vitamin D, Iron Deficiency Anemia, Kisspeptin, Endometriosis, Pregnancy, HPG Axis, Reproductive Health

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