Effects and mechanism of environmental and genetic factors on female puberty and reproduction
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Both environmental and genetic factors can affect female puberty and reproduction. In Chapter 1, these factors with focuses on one environmental factor, genistein, and one genetic factor, olfactomedin 1 (OLFM1) are reviewed. In Chapter 2, the effects of postweaning dietary genistein exposure on female puberty and early pregnancy in C57BL/6J mice are studied. Dose-response study reveals that genistein diets (5-500 ppm) have dose-dependent effects on advancing age at vaginal opening, increasing duration of estrus stage, and accelerating mammary gland development; 5 ppm genistein diet promotes ovulation. Despite the effects on female puberty, postweaning dietary genistein exposure does not have significant effects on early pregnancy. In Chapter 3, the influence of body fat on the effects of genistein on female pubertal development is studied. Berardinelli-Seip Congenital Lipodystrophy 2 (Bscl2)-/- female mice with lipodystropy are used as a low body fat animal model. Postweaning 500 ppm genistein dietary exposure advances vaginal opening and increases mammary gland area in Bscl2-/- females. In Chapter 4, the function and mechanism of OLFM1 on female puberty and fertility using Olfm1-/- mouse model are investigated. Olfm1-/- females have delayed pubertal development and impaired fertility. Rescued ovulation and fertility by superovulation, normal basal Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH) levels, and normal Gonadotropin-releasing hormone (GnRH) induced LH surge indicate a functional Hypothalamus-pituitary-gonad (HPG) axis. High expression level of OLFM1 in the olfactory systems, unresponsiveness to male bedding stimulation on estrous cycle and pubertal development in Olfm1-/- females coupled with a 41% reduction of cFOS positive cells in mitral layer of accessory olfactory bulb indicate that the function of OLFM1 in olfaction contributes to the defective pubertal development and fertility in Olfm1-/- female mice. In Chapter 5, the dissertation and future directions of study are summarized.