Think before you drink.
 “Dry January” can be a struggle for some after the holidays, but new research has revealed that you may be benefiting your own and future offspring’s health. A new study by CNPRC Core Scientist Catherine VandeVoort, PhD, (Fetility and Sterility) identified some of the potential effects of long-term binge drinking episodes on later pregnancies in primates. Binge-levels of alcohol were found to be associated with reduced embryo development, changes in the oocyte and cumulus cell gene expression, and an increase in spontaneous abortion during very early gestation, even after alcohol consumption had ceased.

Binge drinking is an increasing public health concern, especially among college-aged and young adult women. The incidence of binge drinking in the United States continues to increase, and in 2010, occurred in 28% of people aged 18 to 34 years, with an average drink consumption per episode of 9 drinks for men and 5.9 drinks for women. On college campuses, 44% of students report binge drinking, which accounts for 91% of alcohol consumed on campuses.

To determine the effects of binge-type alcohol consumption before ovulation a study was conducted at the California National Primate Research Center (CNPRC) in female rhesus macaques by Dr. VandeVoort, CNPRC Reproductive Sciences and Regenerative Medicine Unit Core Scientist, and Department of Obstetrics and Gynecology, University of California, Davis. Previous to this research, the effects of binge alcohol consumption on fertility had been unknown. Only a few studies evaluating the effects of ethanol on oocyte/early embryo function have been performed, all of which have utilized the mouse model. In vitro exposure of murine embryos to ethanol and acetaldehyde has been shown to impair embryo development. These mouse studies provide a glimpse into one possible mechanism of that effect, but our understanding of how this can affect human health is limited in the murine model.

By utilizing the rhesus monkey, the outcome of these experiments have direct relevance to the effects of binge drinking in women. Nonhuman primates and humans have a high degree of biological similarity in their neurology, immunology, reproduction, and development, and there are many diseases and conditions that can only be studied in nonhuman primates, providing scientists and physicians with irreplaceable opportunities to understand, treat, and prevent human diseases and disorders.

In this research, young adult female rhesus monkeys were trained to drink alcohol on a schedule administered at a level that simulated binge drinking in young women, the equivalent of 4–5 drinks, twice weekly for 6 months. The monkeys were 6 to 12 years (young adult), and had a history of successful pregnancy and normal menstrual cycles. They were indoor-housed and lived in social pairs with another female; however, the females were separated on days when dosing occurred.

The six-month experimental protocol was followed by a standard in vitro fertilization cycle and subsequent natural mating. As soon as pregnancy was detected, all ethanol consumption was discontinued so that only the effects of ethanol on the oocytes and pre-implantation embryos, not the fetus, were the focus of the research.

Oocyte growth and maturation is a process that occurs over many months in primates, including humans and monkeys. Dr. VandeVoort’s research is the first evidence that binge ethanol drinking has the potential to affect oocyte quality and subsequent embryo development, even if alcohol is stopped before the final maturation and fertilization of oocytes. She demonstrates altered follicle cell gene expression, adverse effects on oocyte and cumulus cell gene expression, oocyte quality, early embryogenesis – meiosis and early mitotic divisions of the embryo – and reduced preimplantation embryo development.

The study also revealed an increased rate of spontaneous abortion during very early gestation in ethanol-treated females after natural mating, a previously unappreciated effect of binge ethanol drinking. This is striking, because spontaneous abortion is rare in rhesus monkeys; thus, this finding further highlights the potentially high impact of binge drinking on reproductive function in women.

These observations have major implications for the management of the reproductive health of women, as they reveal potential significant long-term effects on offspring phenotype, even if alcohol consumption is terminated before pregnancy is established or once it is detected.

The biological effects of binge ethanol consumption demonstrated here in a primate model, coupled with the widespread incidence of binge ethanol drinking in the human population, point to an important public health concern that needs to be addressed. Nonhuman primate modeling to study the reproductive biological, molecular, and cellular mechanisms of these effects is needed, along with greater surveillance of binge drinking and its effects on women’s fertility, and on the long-term health consequences for children born subsequent to maternal binge drinking. A better understanding of these interactions could improve women’s reproductive health and reduce the incidences of costly health problems in their children.

“The monkey model is necessary for these studies because the mouse model has little relevance to human health in this area of biology and it is ethically impossible toperform definitive studieson oocytes and embryo development in women. The support of the CNPRC and other National Primate Research Centers by the National Institutes of Health allows these types of critically important studies to be conducted. The highly trained staff and exceptional facilities at the CNPRC made this study possible” states Dr. VandeVoort.

This research was supported by grants from the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, and the Office of Research Infrastructure Programs, Division of Comparative Medicine.

VandeVoort CA, Grimsrud KN, Midic U, Mtango N, Latham KE. Transgenerational effects of binge drinking in a primate model: implications for human health. Fertil Steril. 2014 Dec 6. pii: S0015-0282(14)02311-5.

[Epub ahead of print]