Moderate episodic prenatal alcohol does not impact female offspring fertility in rats

Abstract

25Prenatal alcohol exposure (PAE) has been associated with reproductive dysfunction in 26 offspring. However, studies in females, particularly examining long-term infertility or 27 impacts on ovarian reserve, are lacking. The current study utilised a moderate, episodic 28 exposure model in rats to mimic 'special occasion' drinking, which is reported to be common 29 during pregnancy. Our objective was to examine the consequences of this prenatal alcohol 30 exposure on reproductive parameters in female offspring. Pregnant Sprague Dawley rats were 31 treated with either an ethanol gavage (1g EtOH/kg body weight), or an equivalent volume of 32 saline, on embryonic days 13.5 and 14.5 of pregnancy, resulting in a peak blood alcohol 33 concentration of ~0.04%. Neonatal female offspring were examined for molecular markers 34 regulating early follicle numbers in the ovary and unbiased stereology used to quantify 35 primordial and early growing follicle numbers. Puberty onset (age at vaginal opening and 36 first estrous) was measured post-weaning and estrous cycles, reproductive hormones 37 (progesterone and estradiol) and pregnancy success measured in adults (5-6 months of age). 38 We found no evidence that any of these reproductive parameters were significantly altered by 39 PAE in this model. This animal study provides some reassurance for women who may have 40 consumed a small amount of alcohol during their pregnancy. However, previously published 41 effects on offspring metabolism using this model reinforce avoidance of alcohol during 42 pregnancy. 43 44 45 479 treatments and husbandry; Erica Mu (School of Biomedical Sciences Histology Facility, 480 University of Queensland) for serial sectioning of neonatal ovaries; Shaun Walters (School of 481 Biomedical Sciences Imaging Facility, University of Queensland) for technical assistance 482 with stereology; Tam Nguyen (School of Biomedical Sciences, University of Queensland) for 483 assistance with animal work; and Jacobus Ungerer (Pathology Queensland, Queensland 484 Health) for analysis of BAC. 485 486 21 References 487 Akison, LK, KM Moritz, and N Reid 2019 Adverse reproductive outcomes associated with 488 fetal alcohol exposure: a systematic review. Reproduction 157 329-343. 489 Alviggi, C, P Humaidan, CM Howles, D Tredway, and SG Hillier 2009 Biological versus 490 chronological ovarian age: implications for assisted reproductive technology. Reprod 491 Biol Endocrinol 7 101. 492 Bernal, AB, MH Vickers, MB Hampton, RA Poynton, and DM Sloboda 2010 Maternal 493 undernutrition significantly impacts ovarian follicle number and increases ovarian 494 oxidative stress in adult rat offspring. PLoS One 5 e15558. 495 Boggan, WO, CL Randall, and HM Dodds 1979 Delayed sexual maturation in female 496 C57BL/6J mice prenatally exposed to alcohol. Res Commun Chem Pathol Pharmacol 497 23 117-125. Hansbro, EA McLaughlin, and JE Holt 2016 Maternal smoke exposure impairs the 500 long-term fertility of female offspring in a murine model. Biol Reprod 94 39. 501 Choi, JI, K...