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PubMed2005

The evolutionary origin of signa in female Lepidoptera: natural and sexual selection hypotheses.

Signa are structures of the inner wall of the female corpus bursae (structure where males deposit a spermatophore during copulation) of many Lepidoptera that assist in tearing open spermatophores. In this paper, three hypotheses on the evolutionary origin of signa are proposed. The first hypothesis considers natural selection pressures arising from ecological changes that favor an increase in oviposition rate as the force behind the evolution of signa. The other two hypotheses involve sexual selection. The second hypothesis proposes that sexually antagonistic coevolution is responsible of the evolution of signa: According to this hypothesis, the inverse relation between the length of the female's refractory period and the amount of ejaculate remaining in her corpus bursae, observed in most Lepidoptera studied, selects in males a decreased rate of spermatophore digestion (e.g. a thicker spermatophore envelope or a higher chitin content) that increases the length of the refractory period beyond the female's optimum; in response, females evolved signa as a counteradaptation to restore the female's optimum by increasing the rate of spermatophore digestion. The last hypothesis considers that signa may have evolved as a female device for cryptic choice of males based on the ability of these to influence the length of post-copulatory female refractory period. The different hypotheses make different predictions of the sequence of appearance of specific ecological factors and novel phenotypic traits through evolutionary time. Therefore, testing the relative importance of the hypotheses requires a formal comparative analysis.

Adaptation, Physiological↗
PubMed2005

Phytoestrogenic effects of black tea extract (Camellia sinensis) in an oophorectomized rat (Rattus norvegicus) model of osteoporosis.

The adverse side effects of currently available anti-osteoporotic agents warrant the search for compounds with less toxic effects. In this study, we assessed the phytoestrogenic potentiality of whole aqueous extract of black tea (BTE) in a bilaterally oophorectomized rat model (2.5%, 1 ml/100 g body weight/day for 28 days). Although the supplementation was given for 28 days but, sign of revival of copulation period (estrous stage) from non-receptive diestrous stage was first noticed after 21 days of BTE supplementation in bilaterally oophorectomized rats. This was accompanied by a significant increase in serum estradiol level. To test whether this increase in serum estradiol level could have an influence upon the oophorectomy-induced damage of bone, we assessed marker parameters of bone resorption and osteoclastic activity (tartrate-resistant acid phosphatase), collagen degradation (urinary hydroxyproline), bone loss (bone ash mineral content) and bone breaking strength (bone density). Results indicated that increase in serum estradiol level after BTE supplementation could significantly diminish oophorectomy-induced decaying changes in bone. This study proposes that aqueous BTE may be assessed as a phytoestrogenic compound for prevention against estrogen deficiency-related osteoporotic damages.

Acid Phosphatase↗
PubMed2005

Sympathetic and T helper (Th)2 bias may ameliorate uterine fibroids, independent of sex steroids.

We propose that inadequate sympathetic bias and Th2 bias in the uterine environment contributes to the formation of fibroids, independent of the sex steroid status. We also propose that fibroids represent a modern maladaptation that partly results from decreasing exposure to seminal fluid, which contains catecholalmines, transforming growth factor beta1 (TGFbeta1), aldosterone, prostaglandins, and other factors that shift the uterine environment to sympathetic and T helper (Th)2 bias. Lower risk of fibroids is associated with pre-menarche, post-menopause, pregnancy, exposure to contraceptives, smoking, earlier age of first pregnancy, shorter interval since last pregnancy, higher parity, and non-obesity. These associations are currently attributed to alterations of sex steroids. However, the association may also be explained by the observation that pre-menarche, post-menopause, pregnancy, and smoking represent periods of sympathetic and Th2 bias. Furthermore, use of contraceptives, early age of first pregnancy, short interval since last pregnancy, high parity, abnormal pap smear, and non-obesity may represent surrogates for increased sexual activity and increased exposure to seminal fluid. Catecholalmines, aldosterone, TGF, and prostaglandins are among the seminal fluid components that promote sympathetic and Th2 bias. Vasectomized copulations protect against fibroids, an observation that undermines the steroid hypothesis and supports our hypothesis. The putative mechanism of action of uterine artery embolization (UAE) for fibroid treatment is starvation of blood supply, but the extensive collaterals that protect uterine perfusion would presumably also buffer against fibroid hypoperfusion. Instead, the sympathetic and Th2 responses to UAE-related ischemia may contribute to fibroid regression. A potential explanation for the association of fibroids with intrauterine devices may be a Th1 cell-mediated immune response to the foreign body, which may also enhance the contraceptive effect. Novel methods of preventing and treating fibroids by promoting sympathetic and Th2 shift through natural, pharmacologic, and neuromodulatory means are envisioned. Fibroids are likely a modern dysfunction given the high Darwinian fitness cost of fibroid-related infertility, and may be attributable to reduced intercourse frequency. Fibroids have been observed among animals in captivity that are presumably reproductively isolated.

Female↗
PubMed2004

Nitric oxide mediates glutamate-evoked dopamine release in the medial preoptic area.

Dopamine (DA) release in the medial preoptic area (MPOA) of the hypothalamus is an important facilitator of male sexual behavior. The presence of a receptive female increases extracellular DA in the MPOA, which increases further during copulation. However, the neurochemical events that mediate the increase of DA in the MPOA are not fully understood. Here we report that glutamate, reverse-dialyzed into the MPOA, increased extracellular DA, which returned to baseline after the glutamate was removed. This increase was prevented by co-administration of the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME), but not by the inactive isomer, Nw-nitro-d-arginine methyl ester (D-NAME). In contrast, extracellular concentrations of the major metabolites of DA were decreased by glutamate, suggesting that the DA transporter was inhibited. These decreases were also inhibited by L-NAME, but not D-NAME. These results indicate that glutamate enhances extracellular DA in the MPOA, at least in part, via nitric oxide activity. Therefore, glutamatergic stimulation of nitric oxide synthase may generate the female-induced increase in extracellular DA in the MPOA, which is important for the expression of male sexual behavior.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2004

Distribution of androgen receptor immunoreactivity in the brainstem of male rats.

Gonadal steroids such as testosterone and estrogen are necessary for the normal activation of male rat sexual behavior. The medial preoptic area (MPOA), an important neural substrate regulating mating, accumulates steroids and also expresses functional androgen receptors (AR). The MPOA is intimately connected with other regions implicated in copulation, such as the bed nucleus of the stria terminalis and medial amygdala. Inputs to the MPOA arise from several areas within the brainstem, synapsing preferentially onto steroid sensitive MPOA cells which are activated during sexual activity. Given that little is known about the distribution of AR protein in the brainstem of male rats, we mapped the distribution of AR expressing cells in the pons and medulla using immunocytochemistry. In agreement with previous reports, AR immunoreactivity (AR-ir) was detected in ventral spinal motoneurons and interneurons. In addition, AR-ir was detected in areas corresponding to the solitary tract, lateral paragigantocellular and alpha and ventral divisions of the gigantocellular reticular nuclei, area postrema, raphe pallidus, ambiguus nucleus, and intermediate reticular nucleus. Several regions within the pons contained AR-ir, such as the tegmental and central gray, parabrachial nucleus, locus coeruleus, Barrington's nucleus, periaqueductal gray, and dorsal raphe. In contrast with in situ hybridization studies, auditory and somatosensory areas were AR-ir negative, and, except for very light staining in the prepositus nucleus, areas carrying vestibular information did not display AR-ir. Additionally, cranial nerve motoneurons of the hypoglossal, facial, dorsal vagus, and spinal trigeminal did not display AR-ir in contrast to previous reports. The data presented here indicate that androgens may influence numerous cell groups within the brainstem. Some of these probably constitute a steroid sensitive circuit linking the MPOA to motoneurons in the spinal cord via androgen responsive cells in the caudal ventral medulla.

Animals↗
PubMed2005

Sexual behavior activates the expression of the immediate early genes c-fos and Zenk (egr-1) in catecholaminergic neurons of male Japanese quail.

We analyzed the expression of the immediate early genes c-fos and Zenk (egr-1) in the brain of male quail that were gonadally intact (I) or castrated and treated (CX+T) or not (CX) with testosterone and had been exposed for 60 min either to a sexually mature female (F), or to an empty arena (EA) or were left in their home cage (HC). Alternate sections in the brains collected 90 min after the start of behavioral interactions were stained by immunocytochemistry for the proteins FOS or ZENK alone or in association with tyrosine hydroxylase (TH), a marker of catecholaminergic neurons. C-fos and Zenk expression was statistically increased in six brain areas of sexually active birds (I+F, CX+T+F) compared with controls (CX+F, CX+T+EA, CX+T+HC), i.e. the preoptic area, bed nucleus striae terminalis, arcopallium, nucleus intercollicularis, periaqueductal gray and the ventral tegmental area. Interestingly, c-fos and Zenk expression was high in the nucleus intercollicularis, a midbrain vocal control nucleus, of I+F and CX+T+F birds that displayed copulatory behavior but emitted few crows but not in the nucleus intercollicularis of CX+T+EA birds that crowed frequently. Increases in c-fos expression were observed in TH-immunoreactive cells in the periaqueductal gray and ventral tegmental area, but not in the substantia nigra, of I+F and CX+T+F birds indicating the activation of dopaminergic neurons during sexual behavior. Together, these data confirm the implication of the steroid-sensitive preoptic area and bed nucleus striae terminalis in the control of copulation and support the notion that dopamine is involved in its control.

Animals↗
PubMed2004

Chronic cocaine pretreatment facilitates Pavlovian sexual conditioning in male Japanese quail.

Repeated drug exposure that results in behavioral sensitization has been shown to enhance sex-seeking behaviors in rats as well as facilitate Pavlovian excitatory and inhibitory conditioning. In the present experiment, male Japanese quail were given repeated presentations of cocaine (10 mg/kg, i.p.) that resulted in increased locomotor activity relative to saline. After a 10-day withdrawal period, subjects received sexual conditioning trials that consisted of presentation of an object conditioned stimulus (CS) followed by sexual reinforcement. Results showed that birds that previously received chronic cocaine demonstrated more conditioned approach behavior to the CS object, a shorter latency to copulate with a female, and made more cloacal contacts (copulatory behavior) during sexual reinforcement than saline-treated birds. The findings suggest that chronic cocaine later facilitates Pavlovian conditioning in a sexual behavior paradigm. This may be the result of cocaine facilitating learning via the dopaminergic system. The findings are discussed in the context of the incentive sensitization theory and possible neuronal mechanisms.

Animals↗
PubMed2006

Monoamine levels in the nucleus accumbens correlate with male sexual behavior in middle-aged rats.

The correlation between monoamine levels in the nucleus accumbens (NAcc) and male sexual behavior was studied in middle-aged rats. Male rats (18-19months) were assigned to three groups: (1) Group MIE consisted of rats showing mounts, intromissions, and ejaculations; (2) Group MI was composed of rats showing mounts and intromissions, but no ejaculation; and (3) Group NC were non-copulators showing no sexual behavior. Young adult rats (4-5months), displaying complete copulatory behavior, were used as the control group. Levels of dopamine (DA), serotonin, and norepinephrine and their metabolites in the NAcc were measured by high-pressure liquid chromatography with electrochemical detection. No difference was seen in DA levels between MIE rats and young controls, whereas DA levels in NC rats were significantly lower than those in both MIE and MI rats. Serotonin levels in NC rats were significantly higher than those in MIE and MI rats. Conversely, norepinephrine levels in NC rats were lower than those in MIE rats. These results suggest that monoamine levels in the NAcc correlate with sexual performance in male rats and that changes in NAcc monoamine levels might affect male sexual behavior in middle-aged rats.

Animals↗
PubMed2006

Role of glutamate receptors in the ventromedial hypothalamus in the regulation of female rat sexual behaviors I. Behavioral effects of glutamate and its selective receptor agonists AMPA, NMDA and kainate.

Bilateral infusions of glutamate or kainate to the ventromedial hypothalamus (VMH) have been shown previously to produce a rapid inhibition of lordosis in estrogen-primed female rats induced by manual flank stimulation. The present study examined whether glutamate or selective ionotrophic glutamate receptor agonists can disrupt appetitive and consummatory sexual behaviors following bilateral infusions to the VMH of females during copulation with male rats. Ovariectomized, sexually experienced female rats were implanted bilaterally with guide cannulae aimed at the ventrolateral VMH. After recovery from surgery, females were primed with estradiol benzoate and progesterone and infused with different doses of glutamate, AMPA, NMDA or kainate (n=9-10 in each dose group) 3 min prior to a test with sexually vigorous males in bilevel chambers. Glutamate infusions decreased the display of hops and darts and produced a trend toward decreased lordosis. AMPA infusions decreased the display of solicitations, hops and darts, and lordosis. NMDA infusions decreased lordosis and increased defensive behaviors and pacing. Kainate infusions decreased solicitations, hops and darts, and lordosis, and increased defensive behaviors and pacing. These data indicate that the activation of glutamate receptors in the VMH is inhibitory for both appetitive and consummatory aspects of sexual behavior in the female rat.

Animals↗
PubMed2006

Neural and hormonal control of muscular activity of the spermatheca in the locust, Locusta migratoria.

The spermatheca in insects is a tubular structure within the female that acts as a repository for spermatozoa deposited by the male during copulation. The spermatozoa remain viable within the spermatheca for extended periods of time, and are then delivered to the site of fertilization during oviposition (egg-laying). Thus, the production of viable offspring is dependent upon the coordination of events associated with fertilization, including the passage of the egg through the lateral and common oviducts and the passage of spermatozoa along the spermathecal duct. The egg and the spermatozoa are propelled along their respective tracts by contractions of the visceral muscles intrinsic to the oviduct and spermatheca. The neural and hormonal control of muscular activity of the locust oviducts has been well reviewed, with more recent studies examining the control over the spermatheca. This review highlights more recent literature, including new data, for neural and hormonal control of muscular activity of the spermatheca of the locust, Locusta migratoria, making reference to examples in other insects where relevant. A variety of neuronal types project to the spermatheca in L. migratoria, and a variety of neuroactive chemicals, including neuropeptides and amines, influence contraction. A comparison is made between the control of oviducts and spermatheca in L. migratoria with regard to their neural substrate and the composition of neuroactive chemicals.

Animals↗
PubMed2004

The effects of aromatase inhibition on testosterone-dependent conditioned rhythmic cloacal sphincter movements in male Japanese quail.

Male Japanese quail produce a foam that, along with semen, is transferred to the quail hen during copulation. This foam has been reported to increase fertility, prolong sperm motility, and enhance sperm competition. Action of the cloacal sphincter muscles in response to visual exposure to a female produces the foam. The rhythmic cloacal sphincter movements (RCSM) responsible for foam production in male quail is elicited by a conditioned stimulus (CS) previously paired with access to a quail hen. These conditioned RCSM are testosterone-dependent. The present experiment was conducted to explore whether, as is the case with most other testosterone-dependent male sexual behaviors in the quail, conditioned RCSM are mediated by the aromatization of testosterone. Castrated, testosterone-treated male quail were presented with paired presentations of an arbitrary focal CS and visual access to a female. Once conditioned RCSM had developed, subjects received twice daily injections of the aromatase inhibitor Vorozole (R083842) during a series of extinction test presentations of the CS. Injections of Vorozole significantly decreased the number of RCSMs elicited by a sexual CS. This decrease was specific to sexual RCSM; cloacal sphincter movements that occurred following defecation were not affected by Vorozole. Conditioned sexual RCSM are therefore mediated by the aromatization of testosterone, most likely due to effects on central aromatase activity related to sexual motivation.

Animals↗
PubMed2004

Hormonal regulation of brain circuits mediating male sexual behavior in birds.

Male sexual behavior in both field and laboratory settings has been studied in birds since the 19th century. Birds are valuable for the investigation of the neuroendocrine mechanisms of sexual behavior, because their behavior can be studied in the context of a large amount of field data, well-defined neural circuits related to reproductive behavior have been described, and the avian neuroendocrine system exhibits many examples of marked plasticity. As is the case in other taxa, male sexual behavior in birds can be usefully divided into an appetitive phase consisting of variable behaviors (typically searching and courtship) that allow an individual to converge on a functional outcome, copulation (consummatory phase). Based primarily on experimental studies in ring doves and Japanese quail, it has been shown that testosterone of gonadal origin plays an important role in the activation of both of these aspects of male sexual behavior. Furthermore, the conversion of androgens, such as testosterone, in the brain to estrogens, such as 17beta-estradiol, is essential for the full expression of male-typical behaviors. The localization of sex steroid receptors and the enzyme aromatase in the brain, along with lesion, hormone implant and immediate early gene expression studies, has identified many neural sites related to the control of male behavior. The preoptic area (POA) is a key site for the integration of sensory inputs and the initiation of motor outputs. Furthermore, prominent connections between the POA and the periaqueductal gray (PAG) form a node that is regulated by steroid hormones, receive sensory inputs and send efferent projections to the brainstem and spinal cord that activate male sexual behaviors. The sensory inputs regulating avian male sexual responses, in contrast to most mammalian species, are primarily visual and auditory, so a future challenge will be to identify how these senses impinge on the POA-PAG circuit. Similarly, most avian species do not have an intromittent organ, so the projections from the POA-PAG to the brainstem and spinal cord that control sexual reflexes will be of particular interest to contrast with the well characterized rodent system. With this knowledge, general principles about the organization of male sexual circuits can be elucidated, and comparative studies relating known species variation in avian male sexual behaviors to variation in neural systems can be pursued.

Androgens↗
PubMed2005

Hormonal and social modulation of cloacal muscle activity in female Japanese quail.

Japanese quail are an important model for the discovery of neuroendocrine mechanisms of sexual behavior. In common with most birds and many other vertebrates, there are no genitalia of the mammalian kind (no phallus or vagina). Instead, close contact between the cloacal openings of the male and female is critical for successful mating. Prior research has shown that males produce distinctive rhythmic movements of the foam gland portion of the cloacal sphincter muscle (RCSMs) in response to social stimuli (presentation of a conspecific female or male). These RCSMs enhance the male's fertilization success. Females, unlike males, do not show cloacal sphincter movements to social stimuli (Experiment 1) and female cloacal sphincter muscle activity immediately following copulation does not predict fertilization success (Experiment 2). Females implanted with testosterone propionate (TP), however, show large numbers of male-typical RCSMs in response to social stimuli (Experiment 3). The results of Experiment 3 show that rhythmic movements of the cloacal sphincter muscle shown by TP-treated females are regulated by distal (visual) stimuli and therefore by the brain. They also show that the absence of socially modulated RCSMs in normal females is an activational hormone phenomenon (a sex difference produced by adult hormonal dimorphism), rather than a reflection of prior hormonal organization. These results add to an understanding of the hormonal basis of sex differences in motor mechanisms of sexual behavior in non-mammalian species.

Anal Canal↗
PubMed2004

Has dopamine a physiological role in the control of sexual behavior? A critical review of the evidence.

The role of dopaminergic systems in the control of sexual behavior has been a subject of study for at least 40 years. Not surprisingly, reviews of the area have been published at variable intervals. However, the earlier reviews have been summaries of published research rather than a critical analysis of it. They have focused upon the conclusions presented in the original research papers rather than on evaluating the reliability and functional significance of the data reported to support these conclusions. During the last few years, important new knowledge concerning dopaminergic systems and their behavioral functions as well as the possible role of these systems in sexual behavior has been obtained. For the first time, it is now possible to integrate the data obtained in studies of sexual behavior into the wider context of general dopaminergic functions. To make this possible, we first present an analysis of the nature and organization of sexual behavior followed by a summary of current knowledge about the brain structures of crucial importance for this behavior. We then proceed with a description of the dopaminergic systems within or projecting to these structures. Whenever possible, we also try to include data on the electrophysiological actions of dopamine. Thereafter, we proceed with analyses of pharmacological data and release studies, both in males and in females. Consistently throughout this discussion, we make an effort to distinguish pharmacological effects on sexual behavior from a possible physiological role of dopamine. By pharmacological effects, we mean here drug-induced alterations in behavior that are not the result of the normal actions of synaptically released dopamine in the untreated animal. The conclusion of this endeavor is that pharmacological effects of dopaminergic drugs are variable in both males and females, independently of whether the drugs are administered systemically or intracerebrally. We conclude that the pharmacological data basically reinforce the notion that dopamine is important for motor functions and general arousal. These actions could, in fact, explain most of the effects seen on sexual behavior. Studies of dopamine release, in both males and females, have focused on the nucleus accumbens, a structure with at most a marginal importance for sexual behavior. Since accumbens dopamine release is associated with all kinds of events, aversive as well as appetitive, it can have no specific effect on sexual behavior but promotes arousal and activation of non-specific motor patterns. Preoptic and paraventricular nucleus release of dopamine may have some relationship to mechanisms of ejaculation or to the neuroendocrine consequences of sexual activity or they can be related to other autonomic processes associated with copulation. There is no compelling indication in existing experimental data that dopamine is of any particular importance for sexual motivation. There is experimental evidence showing that it is of no importance for sexual reward.

Animals↗
PubMed2005

Central control of penile erection: role of the paraventricular nucleus of the hypothalamus.

The paraventricular nucleus of the hypothalamus is an integration centre between the central and peripheral autonomic nervous systems. It is involved in numerous functions from feeding, metabolic balance, blood pressure and heart rate, to erectile function and sexual behaviour. In particular, a group of oxytocinergic neurons originating in this nucleus and projecting to extra-hypothalamic brain areas (e.g., hippocampus, medulla oblongata and spinal cord) control penile erection in male rats. Activation of these neurons by dopamine and its agonists, excitatory amino acids (N-methyl-D-aspartic acid) or oxytocin itself, or by electrical stimulation leads to penile erection, while their inhibition by gamma-amino-butyric acid (GABA) and its agonists or by opioid peptides and opiate-like drugs inhibits this sexual response. The activation of these neurons is secondary to the activation of nitric oxide synthase, which produces nitric oxide. Nitric oxide in turn causes, by a mechanism that is as yet unidentified, the release of oxytocin in extra-hypothalamic brain areas. Other compounds recently identified that facilitate penile erection by activating central oxytocinergic neurons are peptide analogues of hexarelin, a growth hormone releasing peptide, pro-VGF-derived peptides, endogenous peptides that may be released by neuronal nerve endings impinging on oxytocinergic cell bodies, SR 141716A, a cannabinoid CB1 receptor antagonist, and, less convincingly, adrenocorticotropin-melanocyte-stimulating hormone (ACTH-MSH)-related peptides. Paraventricular oxytocinergic neurons and similar mechanisms are also involved in penile erection occurring in physiological contexts, namely noncontact erections that occur in male rats in the presence of an inaccessible receptive female, and during copulation. These findings show that the paraventricular nucleus of the hypothalamus plays an important role in the control of erectile function and sexual activity. As the male rat is a model of sexual behaviour and penile physiology, which has largely increased in the last years our knowledge of peripheral and central mechanisms controlling erectile function (drugs that induce penile erection in male rats usually do so also in man), the above results may have great significance in terms of a human perspective for the treatment of erectile dysfunction.

Animals↗
PubMedDate not supplied

Ruta graveolens aqueous extract retards mouse preimplantation embryo development.

This work was undertaken to examine possible embryotoxicity of Ruta graveolens (rue), a plant used by indigenous communities for the purposes of therapeutic and fertility regulation. Superovulated mice were mated and isolated after copulation. They were given aqueous extract of R. graveolens (5, 10, and 20% w/v) or plain water (control) orally for 4 days. Ninety-eight hours post-human chorionic gonadotrophin (hCG), embryos were flushed from oviducts and uterine horns to assess their state of development and extent of embryo transport. Ingestion of rue at 10 and 20% resulted in a high proportion of abnormal embryos (36.7 and 63.6%, respectively, P<0.05). Cell number was diminished (P<0.01) and embryo transport was slightly delayed in the highest dose group. These findings demonstrate that oral administration of R. graveolens extract can interfere with preimplantation development and embryo transport.

Animals↗
PubMedDate not supplied

Intrauterine position and postnatal growth in Sprague-Dawley rats and ICR mice.

In rodents, steroid hormones are thought to be transported between adjacent fetuses, and male or female fetuses that develop in utero between female fetuses may have higher serum levels of estradiol, and lower serum levels of testosterone, relative to siblings of the same sex that develop between two male fetuses. The consequence in the variation of postnatal growth, development, and function in the intrauterine position, using various parameters such as anogenital distance, preputial separation and vaginal opening, estrous cycle, locomotor activity, and growth of reproductive organs, were examined in Sprague-Dawley rats. ICR mice were treated with 17beta-estradiol before copulation and during pregnancy to address the interaction with endogenous estradiol during pregnancy. In rats, no evidence of effects of prior intrauterine position was observed for any of the parameters examined. Mouse fetal exposure via the mother to low-dose 17beta-estradiol revealed no changes in the rate of postnatal growth in males and females that developed in any intrauterine position in utero. The results of this study suggested that the intrauterine position of the embryos/fetuses did not affect the postnatal growth of the reproductive organs, sexual maturation, or behavior in rats and mice.

Anal Canal↗
PubMed2004

Developmental effects of inhalation exposure to 2-bromopropane in rats.

2-Bromopropane (2-BP), known as a reproductive and hematopoietic toxicant in humans, was assessed for developmental toxicity. Sprague-Dawley rats were exposed by inhalation to 2-BP at a concentration of 0 (control), 125, 250, 500, or 1000 ppm for 6 h per day, 7 days per week during 2 weeks of the pre-mating period, during the mating period until copulation and during the period of gestation days 0-19. After parturition, dams were allowed to breast feed their pups until postnatal day 4. 2-BP exposure resulted in no signs of maternal toxicity as assessed by clinical observations and body weight gain. On the other hand, the inhalation exposure to 1000 ppm markedly decreased the number of pups born, although the number of implantations did not decrease. No effect of 2-BP on pups weights or survival until postnatal day 4 was found. It was found that the repeated inhalation exposure of rats to 1000 ppm 2-BP induced fetal lethality during the post-implantation period.

Abnormalities, Drug-Induced↗