Critical Windows of Exposure for Children's Health: The Reproductive System in Animals and Humans

Abstract

Drugs and environmental chemicals can adversely affect the reproductive system. Currently, available data indicate that the consequences of exposure depend on the nature of the chemical, its target, and the timing of exposure relative to critical windows in development of the reproductive system. The reproductive system is designed to produce gametes in far greater excess than would seem to be necessary for the survival of species. Ten to hundreds of millions of spermatozoa are generated daily by most adult male mammals, yet very few of these germ cells succeed in transmitting their genetic material to the next generation. Although the number of oocytes produced in mammalian females is more limited, and their production occurs only during fetal life, most ovaries contain several orders of magnitude more oocytes than ever will be fertilized. Toxicant exposures may affect critical events in the development of the reproductive system, ranging from early primordial germ cell determination to gonadal differentiation, gametogenesis, external genitalia, or signaling events regulating sexual behavior. Although there are differences between the human reproductive system and that of the usual animal models, such models have been extremely useful in assessing risks for key human reproductive and developmental processes. The objectives for future studies should include the elucidation of the specific cellular and molecular targets of known toxicants; the design of a systematic approach to the identification of reproductive toxicants; and the development of sensitive, specific, and predictive animal models, minimally invasive surrogate markers, or in vitro tests to assess reproductive system function during embryonic, postnatal, and adult life.

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

“…hypospadias and cryptorchidism in humans), in puberty (as delay or precocity), or in adulthood (e.g. infertility, alterations in accessory sex organs, disturbances in pregnancy maintenance, endometriosis, or premature reproductive senescence) (Pryor et al, 2000;Buck Louis et al, 2005). In the following, we discuss some specific chemicals that have been reported to affect one or several reproductive outcomes.…”

DDT reintroduction for malaria control: the cost-benefit debate for public health

“…Such time periods (during which the reproductive system's development is more susceptible to transformations, including those produced by xenobiotics) have been well characterized in the scientific literature 20,21,22 .…”

“…Preconceptional exposures are defined here as those affecting spermatogenesis in men, while in women this phase corresponds to the point at which the gametes emerge from the primordial follicular state and proceed to the primary and secondary follicles and become fertile 21 . The prenatal period is divided into two phases: the first phase ranges from fertilization until genital development.…”

The influence of amifostine administration prior to cyclophosphamide on in vitro maturation of mouse oocytes

“…Cyclophosphamide (CP) is a chemotherapy and immunosuppressive agent and it is widely used in treatment of neoplastic disease such as breast carcinoma, acute lymphoblastic leukemia, non Hodgkin's lymphoma, and variety of tissue sarcomas [1,2]. It is converted to alkylating agents in liver [3].…”