Perturbation of male sexual behavior in mice (Mus musculus) within a discrete range of perinatal bisphenol-A doses in the context of a high- or low-phytoestrogen diet.

Differentiation of masculine and feminine behavior in mammals depends on perinatal sex steroids. As bisphenol-A (BPA) can be estrogenic and anti-androgenic, we examined impacts of perinatal exposure upon adult sexual behavior and morphology of male mice. In Experiment 1, dams were fed either a high- or low-phytoestrogen diet and received daily oral doses of 0, 0.175, 1.75, or 17.5µg BPA from gestation day 10 through post-partum day 9. Male offspring from the high-phytoestrogen plus 17.5µg BPA condition showed reduced mass of vesicular-coagulating but not other male glands, and showed increased latency to insemination when paired with females. In Experiment 2, these procedures were replicated but with all animals fed the high-phytoestrogen diet and perinatal BPA doses of 0, 17.5, 175, or 1750µg/day. Adult masses of testes and male-accessory glands and levels of urinary steroids were not significantly affected. When males each encountered a sexually receptive female, there were fewer intromissions among those given 17.5 or 175µg and fewer ejaculations among those given 17.5µg, but the 1750µg dose had no effect. Perinatal BPA dosages thus influenced male sexual behavior non-monotonically, with impairment evident in a discrete dose range among males on a high-phytoestrogen diet.

Transfer of [³H]estradiol-17ß and [³H]progesterone from conspecifics to cohabiting female mice.

Estradiol-17ß (E2) and progesterone (P4) play critical roles in female reproductive physiology and behavior. Given the sensitivity of females to exogenous sources of these steroids, we examined the presence of E2 and P4 in conspecifics' excretions and the transfer of excreted steroids between conspecifics. We paired individual adult female mice with a stimulus male or female conspecific given daily injections of [³H]E2 or [³H]P4. Following 48  h of direct interaction with the stimulus animal, we measured radioactivity in the uterus, ovaries, muscle, olfactory bulbs, mesencephalon and diencephalon (MC+DC), and cerebral cortex of the untreated female cohabitant. Radioactivity was significantly present in all tissues of female subjects after individual exposure to a stimulus male or female given [³H]E2. In females exposed to males given [³H]P4, radioactivity was significantly present in the uterus, ovaries, and muscle, but not in other tissues. In females exposed to stimulus females given [³H]P4, radioactivity was significantly present in all tissues except the MC+DC. In mice directly administered [³H]steroids, greater radioactivity was found in the urine of females than of males. Among females directly administered [³H]steroids, greater radioactivity was found in urine of those given [³H]P4 than of those given [³H]E2. When females were administered unlabeled E2 before exposure to [³H]E2-treated females, less radioactivity was detected in most tissues than was detected in the tissues of untreated females exposed to [³H]E2-treated females. We suggest that steroid transfer among individuals has implications for the understanding of various forms of pheromonal activity.

Oestradiol transmission from males to females in the context of the Bruce and Vandenbergh effects in mice (Mus musculus).

Male mice actively direct their urine at nearby females, and this urine reliably contains unconjugated oestradiol (E(2)) and other steroids. Giving inseminated females minute doses of exogenous E(2), either systemically or intranasally, can cause failure of blastocyst implantation. Giving juvenile females minute doses of exogenous E(2) promotes measures of reproductive maturity such as uterine mass. Here we show that tritium-labelled E(2) ((3)H-E(2)) can be traced from injection into novel male mice to tissues of cohabiting inseminated and juvenile females. We show the presence of (3)H-E(2) in male excretions, transmission to the circulation of females and arrival in the female reproductive tract. In males, (3)H-E(2) given systemically was readily found in reproductive tissues and was especially abundant in bladder urine. In females, (3)H-E(2) was found to enter the system via both nasal and percutaneous routes, and was measurable in the uterus and other tissues. As supraoptimal E(2) levels can both interfere with blastocyst implantation in inseminated females and promote uterine growth in juvenile females, we suggest that absorption of male-excreted E(2) can account for major aspects of the Bruce and Vandenbergh effects.

Excretion and binding of tritium-labelled oestradiol in mice (Mus musculus): implications for the Bruce effect.

Male mouse urine contains 17beta-oestradiol (E(2)) and other steroids. Given that males actively direct urine at proximate females and intrauterine implantation of blastocysts is vulnerable to minute amounts of exogenous oestrogens, males' capacity to disrupt early pregnancy could be mediated by steroids in their urine. When male mice were implanted with osmotic pumps containing tritium-labelled E(2) ((3)H-E(2)) or injected i.p. with (3)H-E(2), radioactivity was reliably detected in their urine. Following intranasal administration of (3)H-E(2) to inseminated females, radioactivity was detected in diverse tissue samples, with there being significantly more in reproductive tissues than in brain tissues. When urine was taken from males injected with (3)H-E(2), and then intranasally administered to inseminated females, radioactivity was detected in the uterus, olfactory bulbs, and mesencephalon and diencephalon (MC+DC). When inseminated and ovariectomised females were perfused at the point of killing to remove blood from tissues, more radioactivity was detected in the uterus than in muscle, olfactory bulbs, MC+DC and cerebral cortex. Pre-treatment with unlabelled E(2) significantly reduced the uptake of (3)H-E(2) in the uterus. Taken with evidence that males deliver their urine to the nasal area of females, these results indicate that male urinary E(2) arrives in tissues, including the uterus, where it could lead to the disruption of blastocyst implantation.