© 2021 Society for Reproduction and Fertility https://doi.org/10.1530/REP-20-0316
ISSN 1470–1626 (paper) 1741–7899 (online) Online version via https://rep.bioscientifica.com
REPRODUCTION
RESEARCH
Parents ethanol use impairs ethanol-naive offspring
development and reproduction
Vanessa Caroline Fioravante
1,2
, Alana Rezende Godoi
1,2
, Victória Mokarzel de Barros Camargo
1,2
,
Renata Steffany do Nascimento
1
, Patricia Fernanda Felipe Pinheiro
1
and
Francisco Eduardo Martinez
1
1
Department of Structural and Functional Biology, Institute of Biosciences of Botucatu (IBB), UNESP – Univ
Estadual Paulista, São Paulo, Brazil and
2
General and Applied Biology Program, Institute of Biosciences of Botucatu
(IBB), UNESP – Univ Estadual Paulista, São Paulo, Brazil
Correspondence should be addressed to F E Martinez; Email: fe.martinez@unesp.br
Abstract
Parental ethanol consumption can infuence the offspring phenotype. In this way, we analyzed the impairments of maternal and
paternal high ethanol consumption during postpuberty on the physical development, feeding pattern, puberty onset and reproductive
function of ethanol-naive offspring to birth to adulthood. Female and male UChB rats (voluntary 10%, v/v ethanol consumer) were
divided into a control group (C) and an ethanol exposed group (E) from 65 to 80 days of age. The C and E were mated at 100 days.
The maternal parameters and offspring development and reproduction parameters were monitored. We observed reduced feeding
intake and body weight in the dams of E group throughout gestation and lactation period. Delay in physical development, lower body
weight and altered feeding pattern were observed in female and male offspring of E group. In addition, the puberty onset was delayed
in both sexes, with lower testosterone levels in the juvenile and pubertal males. There was a prolongation on the estrous and proestrus
phases in females from E but the estrous cycle duration did not change between groups. Ovary and uterus weight were reduced in
pubertal and adult females from E group. Reduced epididymis and seminal vesicle weight, increased sperm abnormalities, decrease in
the daily sperm production and accelerated epididymal transit time were observed in E males. The high maternal and paternal ethanol
use on postpuberty impairs the parameters of ethanol-naive offspring inducing alteration on development and reproduction.
Reproduction (2021) 161 195–204
Introduction
Ethanol is one of the main abuse drugs ingested
worldwide (Rehm et al. 2009, Balddin et al. 2018) and
responsible for approximately 5.2% of global deaths
(GBD 2018). Chronic alcohol intake can result in
female and male reproductive pathologies confrmed
in experimental models (Oremosu & Akang 2015,
Srivastava et al. 2018) and humans (Eggert et al. 2004,
Sansone et al. 2018). Its toxic molecules can harm the
gonads and lead to oxidative stress which damages the
integrity of the germinative DNA and, consequently,
embryo development (Jana et al. 2010, Fan et al. 2017).
Maternal alcohol consumption is capable of
restricting fetal growth and impairing the offspring
development (Weinberg et al. 2008, Brix et al. 2020).
Thus, an adverse intrauterine environment can
program the growth and development of the main
physiological or behavioral systems to improve the
adaptation and survival of adulthood offspring (Zhang
et al. 2005). Different phenotypes can be produced by
development programming, highlighting the plasticity
of the offspring adaptation (Zhang et al. 2005, Rando
& Simmons 2015). However, these early adaptations
may increase the propensity of disorders in adulthood
(Hochberg et al. 2011). Additionally, besides fetal
programming conducted by the uterine environment, it
has been established that paternal exposure also plays
an important role in offspring development (Lane et al.
2014, Bedi et al. 2019).
In this perspective, preconception experiences,
maternal or paternal, as the nutrition, metabolic status
and toxicants exposure have been associated with
embryonic, fetal and postnatal development (Lane
et al. 2014, Öst et al. 2014). Thus, lifestyle can defne
the offspring development patterns. However, the
molecular mechanisms which hereditarily infuence the
phenotypes are poorly understood (Bedi et al. 2019).
Ethanol-induced epigenetic mechanisms, capable of
modifying the expression pattern of different tissues
(Asimes et al. 2017), is one of the mechanisms related to
changes in descendants’ phenotypes.
Studies in rodents have shown that prepuberty,
puberty, or conception ethanol exposure can be
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