Nonsteroidal anti-inflammatory drugs (
NSAIDs), such as
aspirin (
acetylsalicylic acid),
diclofenac and
ibuprofen (IBU), and
analgesic drugs, such as
acetaminophen (
APAP, or
paracetamol), are widely used to treat
inflammation and
pain.
APAP and IBU are
over-the-counter drugs and are among the most commonly taken drugs in the first trimester of pregnancy, even in combination. Furthermore, these drugs and their metabolites are released in the environment, and can be frequently detected in
wastewater, surface water, and importantly in
drinking water. Although their environmental concentrations are much lower than the
therapeutics doses, this suggests an uncontrolled low-dose exposure of the general population, including pregnant women and young children, two particularly at risk populations. Epidemiological studies show that exposure to these molecules in the first and second trimester of gestation can favor genital malformations in new-born boys. To investigate the cellular, molecular and mechanistic effects of exposure to these molecules, ex vivo studies with human or rodent gonadal explants and in vivo experiments in rodents have been performed in the past years. This review recapitulates recent data obtained in rodent models after in utero or postnatal exposure to these drugs. The first part of this review discusses the mechanisms by which
NSAIDs and
analgesics may impair gonadal development and maturation, puberty development, sex
hormone production, maturation and function of adult organs, and ultimately fertility in the exposed animals and their offspring. Like other
endocrine disruptors,
NSAIDs and
APAP interfere with endocrine gland function and may have inter/transgenerational adverse effects. Particularly, they may target germ cells, resulting in reduced quality of male and female gametes, and decreased fertility of exposed individuals and their descendants. Then, this review discusses the effects of exposure to a single drug (
APAP,
aspirin, or IBU) or to combinations of drugs during early embryogenesis, and the consequences on postnatal gonadal development and adult reproductive health. Altogether, these data may increase medical and public awareness about these reproductive health concerns, particularly in women of childbearing age, pregnant women, and parents of young children.