Prenatal Alcohol Exposure and Pair Feeding Differentially Impact Puberty and Reproductive Development in Female Rats: Role of the Kisspeptin System.
Reproductive maturation is initiated with the onset of puberty, which activates the hypothalamic-pituitary-gonadal axis and coincidences with increased expression of the hormone kisspeptin within the hypothalamus. Maturational events are sensitive to environmental factors, including alcohol, which is known to delay reproductive development. We hypothesized that, similar to alcohol's adverse effects during reproductive maturation, prenatal alcohol exposure (PAE) would alter pubertal markers, sex hormone profiles, and kisspeptin expression in the hypothalamus.



Female offspring from control (C), pair-fed (PF), and PAE groups were sacrificed prior to puberty onset (postnatal day [PND] 30), during puberty [PND 35], or in adulthood [PND 65]. Estradiol (E2), progesterone (P4), prolactin, and luteinizing hormone levels, and Kiss1 mRNA expression were measured in the arcuate (ARC) and anteroventral periventricular (AVPV) nuclei of the hypothalamus. Pubertal markers (vaginal opening [VO], uterus/body wt ratio) were assessed.



Our findings indicate that (i) PAE inhibits the expected increases in E2levels with age and delays maturational increases of P4levels; (ii) PAE and pair feeding have similar adverse effects on VO and uterus/body wt ratio; (iii) differential relationships between PRL and P4suggest that different mechanisms may underlie delayed maturation in PAE and PF; that is, PF females have low PRL levels and no increase in P4with age, whereas PAE animals, despite low PRL, show the expected age-related increase in P4; and (iv) there is higher mean density of Kiss1 mRNA in the ARC of adult PAE females and altered Kiss1 expression in the AVPV of both PAE and PF females.



PAE and pair feeding have some overlapping but important differential effects on hormonal profiles and Kiss1 mRNA expression during reproductive development. Preadolescent alterations in Kiss1 expression in the AVPV and ARC, which may change the balance of function in these 2 nuclei, may differentially contribute to delayed reproductive maturation in PAE and PF compared to C females.
Department of Cellular & Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada. joanna.sliwowska@gmail.com.|Laboratory of Neurobiology, Department of Veterinary Medicine and Animal Sciences, Institute of Zoology, Poznan University of Life Sciences, Poznan, Poland. joanna.sliwowska@gmail.com.
Joanna Helena
JH
Sliwowska
Department of Cellular & Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Wendy L
WL
Comeau
Department of Cellular & Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Tamara S
TS
Bodnar
Department of Cellular & Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Linda
L
Ellis
Department of Cellular & Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Joanne
J
Weinberg
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism*; D007032:Hypothalamus, Anterior / Q000378:metabolism; D059648:Kisspeptins / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011374:Progesterone / Q000097:blood; D011388:Prolactin / Q000097:blood; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000187:drug effects*
C491406:Kiss1 protein, rat; D059648:Kisspeptins; D011374:Progesterone; D004958:Estradiol; D011388:Prolactin; D007986:Luteinizing Hormone
Kisspeptin; Pair Feeding; Prenatal Alcohol (Ethanol); Puberty; Sex Hormones
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