TY - JOUR
T1 - Maternal Vitamin D deficiency programs reproductive dysfunction in female mice offspring through adverse effects on the neuroendocrine axis
AU - Nicholas, Cari
AU - Davis, Joseph
AU - Fisher, Thomas
AU - Segal, Thalia
AU - Petti, Marilena
AU - Sun, Yan
AU - Wolfe, Andrew
AU - Neal-Perry, Genevieve
N1 - Publisher Copyright:
Copyright © 2016 by the Endocrine Society.
PY - 2016/4
Y1 - 2016/4
N2 - Vitamin D (VitD) deficiency affects more than 1 billion people worldwide with a higher prevalence in reproductive-aged women and children. The physiological effects of maternal VitD deficiency on the reproductive health of the offspring has not been studied. To determine whether maternal VitD deficiency affects reproductive physiology in female offspring, we monitored the reproductive physiology of C57BL/6J female offspring exposed to diet-induced maternal VitD deficiency at three specific developmental stages: 1) in utero, 2) preweaning, or 3) in utero and preweaning. We hypothesized that exposure to maternal VitD deficiency disrupts reproductive function in exposed female offspring. To test this hypothesis, we assessed vaginal opening and cytology and ovary and pituitary function as well as gonadotropin and gonadal steroid levels in female offspring. The in utero, preweaning, and in utero and preweaning VitD deficiency did not affect puberty. However, all female mice exposed to maternal VitD deficiency developed prolonged and irregular estrous cycles characterized by oligoovulation and extended periods of diestrus. Despite similar gonadal steroid levels and GnRH neuron density, females exposed to maternal VitD deficiency released less LH on the evening of proestrus. When compared with control female offspring, there was no significant difference in the ability of females exposed to maternal VitD deficiency to respond robustly to exogenous GnRH peptide or controlled ovarian hyperstimulation. These findings suggest that maternal VitD deficiency programs reproductive dysfunction in adult female offspring through adverse effects on hypothalamic function.
AB - Vitamin D (VitD) deficiency affects more than 1 billion people worldwide with a higher prevalence in reproductive-aged women and children. The physiological effects of maternal VitD deficiency on the reproductive health of the offspring has not been studied. To determine whether maternal VitD deficiency affects reproductive physiology in female offspring, we monitored the reproductive physiology of C57BL/6J female offspring exposed to diet-induced maternal VitD deficiency at three specific developmental stages: 1) in utero, 2) preweaning, or 3) in utero and preweaning. We hypothesized that exposure to maternal VitD deficiency disrupts reproductive function in exposed female offspring. To test this hypothesis, we assessed vaginal opening and cytology and ovary and pituitary function as well as gonadotropin and gonadal steroid levels in female offspring. The in utero, preweaning, and in utero and preweaning VitD deficiency did not affect puberty. However, all female mice exposed to maternal VitD deficiency developed prolonged and irregular estrous cycles characterized by oligoovulation and extended periods of diestrus. Despite similar gonadal steroid levels and GnRH neuron density, females exposed to maternal VitD deficiency released less LH on the evening of proestrus. When compared with control female offspring, there was no significant difference in the ability of females exposed to maternal VitD deficiency to respond robustly to exogenous GnRH peptide or controlled ovarian hyperstimulation. These findings suggest that maternal VitD deficiency programs reproductive dysfunction in adult female offspring through adverse effects on hypothalamic function.
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U2 - 10.1210/en.2015-1638
DO - 10.1210/en.2015-1638
M3 - Article
C2 - 26741195
AN - SCOPUS:84964434475
SN - 0013-7227
VL - 157
SP - 1535
EP - 1545
JO - Endocrinology
JF - Endocrinology
IS - 4
ER -