Transgenerational effects of Di (2-ethylhexyl) phthalate in the male CRL:CD(SD) rat: added value of assessing multiple offspring per litter.

In the rat, some phthalates alter sexual differentiation at relatively low dosage levels by altering fetal Leydig cell development and hormone synthesis, thereby inducing abnormalities of the testis, gubernacular ligaments, epididymis, and other androgen-dependent tissues. In order to define the dose-response relationship between di(2-ethylhexyl) phthalate (DEHP) and the Phthalate Syndrome of reproductive alterations in F1 male rats, Sprague-Dawley (SD) rat dams were dosed by gavage from gestational day 8 to day 17 of lactation with 0, 11, 33, 100, or 300 mg/kg/day DEHP (71-93 males per dose from 12 to 14 litters per dose). Some of the male offspring continued to be exposed to DEHP via gavage from 18 days of age to necropsy at 63-65 days of age (PUB cohort; 16-20/dose).

Prenatal testosterone exposure permanently masculinizes anogenital distance, nipple development, and reproductive tract morphology in female Sprague-Dawley rats.

In mammals, abnormal increases in fetal androgens disrupt normal development of the female phenotype. Due to the recent concern regarding environmental androgen-active chemicals, there is a need to identify sources of fetal androgen variation and sensitive developmental markers for androgenic activity in female rats. Anogenital distances (AGD), nipple retention, reproductive tract, and external genitalia are morphological parameters organized by prenatal androgens and are predictive of altered masculinized/defeminized phenotype in adult female mice and rats.

Chronic di-n-butyl phthalate exposure in rats reduces fertility and alters ovarian function during pregnancy in female Long Evans hooded rats.

Testis function in fetal and peripubertal male rats is disrupted by subchronic exposure to phthalate esters (PEs). In contrast to the male rat, it is generally held that reproduction in female rats is much less sensitive to phthalate-induced disruption. However, the current study demonstrates that oral administration of dibutyl phthalate (DBP) to female Long Evans (LE) hooded rats from weaning, through puberty, mating, and gestation disrupts pregnancy maintenance at dose levels similar to those that affect testis function in male rats.

Hershberger assay to investigate the effects of endocrine-disrupting compounds with androgenic or antiandrogenic activity in castrate-immature male rats.

The protocol described in this unit is designed to evaluate the effects of androgenic and antiandrogenic endocrine-disrupting compounds (EDCs) in the castrate-immature male rat. Continuous 10-day exposure of the prepubertal male to chemicals is used to identify androgenic or antiandrogenic activities based on the weights of several androgen-dependent tissues on the day after treatment is ended. Androgen-dependent organ weights and growth, along with kidney, liver, and adrenal weights are measured at necropsy.

Late gestational exposure to the fungicide prochloraz delays the onset of parturition and causes reproductive malformations in male but not female rat offspring.

Prochloraz (PZ) is an imidazole fungicide that displays multiple endocrine activities. It inhibits steroid synthesis via P450 modulation and acts as an androgen receptor (AR) antagonist, but its effects on male sexual differentiation have not been described. The purpose of the current study was to expand in vitro observations and to determine whether PZ affected sexual differentiation.

Transgenerational (in utero/lactational) exposure to investigate the effects of endocrine disrupting compounds (EDCS) in rats.

This protocol is designed to evaluate the effects of endocrine disrupting compounds (EDCs) through fetal (transplacental) and/or neonatal (via the dam's milk) exposure during the critical periods of reproductive organogenesis in the rat. Continued direct exposure to the F1 pups after weaning is an option that can also be included. Reproductive indices, growth, and viability are monitored throughout the life of the F1 generation and an extensive necropsy is conducted after sexual maturity is attained.

Phthalate ester-induced gubernacular lesions are associated with reduced insl3 gene expression in the fetal rat testis.

Targeted inactivation of the insulin-like hormone 3 (insl3) gene in male mice results in altered gubernacular development, disrupted testis decent, and cryptorchidism. Cryptorchidism is a fairly common human malformation, being displayed in about three males per 100 at birth, but only a small percentage can be linked directly to genetic defects. The phthalate esters (PEs) are high production volume, ubiquitous environmental chemicals, some of which when administered during sexual differentiation, induce male rat reproductive tract malformations including gubernacular agenesis.

Effects of prenatal testosterone propionate on the sexual development of male and female rats: a dose-response study.

Testosterone plays a major role in male sexual development. Exposure of females to testosterone in utero can induce masculine characteristics such as anovulation, increased anogenital distance (AGD), absence of nipples, retention of male-like tissues, and agenesis of the lower vagina. In addition, high levels of androgens during fetal development can lead to toxic effects such as reduced litter size and viability.