Abnormalities Of Reproductive Organs Research Articles

Ethynylestradiol feminizes gene expression partly in testis developing as ovotestis and disrupts asymmetric Müllerian duct development by eliminating asymmetric gene expression in Japanese quail embryos.

In avian embryos, xenoestrogens induce abnormalities in reproductive organs, particularly the testes and Müllerian ducts (MDs). However, the molecular mechanisms remain poorly understood. We investigated the effects of ethynylestradiol (EE2) exposure on gene expression associated with reproductive organ development in Japanese quail embryos. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis revealed that the left testis containing ovary-like tissues following EE2 exposure highly expressed the genes for steroidogenic enzymes (P450scc, P45017α, lyase, and 3β-HSD) and estrogen receptor-β, compared to the right testis. No asymmetry was found in these gene expression without EE2. EE2 induced hypertrophy in female MDs and suppressed atrophy in male MDs on both sides. RNA sequencing analysis of female MDs showed 1,366 differentially expressed genes between developing left MD and atrophied right MD in the absence of EE2, and these genes were enriched in Gene Ontology terms related to organogenesis, including cell proliferation, migration and differentiation, and angiogenesis. However, EE2 reduced asymmetrically expressed genes to 21. RT-qPCR analysis indicated that genes promoting cell cycle progression and oncogenesis were more highly expressed in the left MD than in the right MD, but EE2 eliminated such asymmetric gene expression by increasing levels on the right side. EE2-exposed males showed overexpression of these genes in both MDs. This study reveals part of the molecular basis of xenoestrogen-induced abnormalities in avian reproductive organs, where EE2 may partly feminize gene expression in the left testis, developing as the ovotestis, and induce bilateral MD malformation by canceling asymmetric gene expression underlying MD development.

GPER and Testicular Germ Cell Cancer.

The G protein-coupled estrogen receptor (GPER), also known as GPR30, is a widely conserved 7-transmembrane-domain protein which has been identified as a novel 17β-estradiol-binding protein that is structurally distinct from the classic oestrogen receptors (ERα and ERβ). There are still conflicting data regarding the exact role and the natural ligand of GPER/GPR30 in reproductive tracts as both male and female knock-out mice are fertile and have no abnormalities of reproductive organs. Testicular germ cell cancers (TGCCs) are the most common malignancy in young males and the most frequent cause of death from solid tumors in this age group. Clinical and experimental studies suggested that estrogens participate in the physiological and pathological control of male germ cell proliferation. In human seminoma cell line, while 17β-estradiol (E2) inhibits in vitro cell proliferation through an ERβ-dependent mechanism, an impermeable E2 conjugate (E2 coupled to BSA), in vitro cell proliferation is stimulated by activating ERK1/2 and protein kinase A through a membrane GPCR that we further identified as GPER/GPR30. The same effect was observed with low but environmentally relevant doses of BPA, an estrogenic endocrine disrupting compound. Furthermore, GPER/GPR30 is specifically overexpressed in seminomas but not in non-seminomas and this overexpression is correlated with an ERβ-downregulation. This GPER/GPR30 overexpression could be linked to some genetic variations, as single nucleotide polymorphisms, which was also reported in other hormone-dependent cancers. We will review here the implication of GPER/GPR30 in TGCCs pathophysiology and the arguments to consider GPER/GPR30 as a potential therapeutic target in humans.

The effectiveness of Heatsynch protocol in dairy cows with abnormalities of reproductive organ

The aim of this study was to determine the incidence of abnormalities of reproductive organs, and to determine the effectiveness of Heatsynchprotocol in dairy cows that suffered from abnormalities of reproductive organs. This study was conducted in smallholder dairy farms in Panette, Cendana Sub-district, Enrekang Regency and the study was conducted in two stages. The first stage; a total of 77 dairy cows were used to determine the incidence of reproductive organs abnormalities. The second stage; a total of 20 dairy cows that suffered from reproductive organs abnormalities were divided into two groups. The first 10 dairy cows were treated with Heatsynch, and the other 10 dairy cows were used as a negative control (without Heatsynch treatment). For positive control, 10 dairy cows that did not suffered from abnormalities of reproduction organs were used. The results of this study showed that the incidence of reproductive organs abnormalities was 36.4% and the highest of abnormalities was uterine disorders at 26%. The percentage of cows suffered from reproductive organs abnormalities that became pregnant after treated with Heatsynch was 60%, while none cows become pregnant without treatment. The average interval from calving to pregnancy in Heatsynch group was 512 days, and in control negative cows, none become pregnant up to 557 days after calving. It can be concluded that the incidence of abnormalities of reproductive organs in dairy cattle was still high. The Heatsynchprotocol can improve the abnormalities of the reproductive organs in the dairy cows and improve reproductive efficiency by increase the pregnancy rate and shortening calving interval.

Evaluation of the effects of low concentrations of bisphenol AF on gonadal development using the Xenopus laevis model: A finding of testicular differentiation inhibition coupled with feminization

Developmental exposures to estrogenic chemicals possibly cause structural and functional abnormalities of reproductive organs in vertebrates. Bisphenol AF (BPAF), a bisphenol A (BPA) analogue, has been shown to have higher estrogenic activity than BPA, but little is known about the effects of BPAF on gonadal development, particularly gonadal differentiation. We aimed to determine whether low concentrations of BPAF could disrupt gonadal differentiation and subsequent development using Xenopus laevis, a model species for studying feminizing effects of estrogenic chemicals. X. laevis tadpoles were exposed to BPAF (1, 10, 100 nM) or 17β-estradiol (E2, positive control) from stages 45/46 to 53 and 66 in a semi-static exposure system, with a prolonged treatment with the highest concentration to the eighth week post-metamorphosis (WPM8). Gonadal morphology and histology as well as sexually dimorphic gene expression were examined to evaluate the effects of BPAF. All concentrations of BPAF caused changes in testicular morphology at different developmental stages compared with controls. Specifically, at stage 53, BPAF like E2 resulted in decreases in both the size and the number of gonadal metameres (gonomeres) in testes, looking like ovaries. Some of BPAF-treated testes remained segmented and even became discontinuous and fragmented at subsequent stages. Histological abnormalities were also observed in BPAF-treated testes, such as ovarian cavity at stages 53 and 66 and poorly developed seminiferous tubules on WPM8. At the molecular level, BPAF inhibited expression of male highly expressed genes in testes at stage 53. Correspondingly, BPAF, like E2, inhibited cell proliferation in testes at stage 50. All results show that low concentrations of BPAF inhibited testicular differentiation and subsequent development in X. laevis, along with feminizing effects to some degree. Our finding implies a risk of BPAF to the male reproductive system of vertebrates including humans.

Roles of phytohormone changes in the grain yield of rice plants exposed to heat: a review.

During its reproductive phase, rice is susceptible to heat stress. Heat events will occur at all stages during the reproductive phase of rice as a result of global warming. Moreover, rice yield traits respond differently to heat stress during panicle initiation, flowering and grain filling. The reduction in the number of spikelets per panicle of heat-stressed plants is due to the attenuated differentiation of secondary branches and their attached florets as well as the promotion of their degradation during the panicle-initiation stage but is not affected by heat stress thereafter. Spikelet sterility as a result of heat stress is attributed not only to physiological abnormalities in the reproductive organs during the flowering stage but also to structural and morphological abnormalities in reproductive organs during the panicle-initiation stage. The reduced grain weight of heat-stressed plants is due to a reduction in nonstructural carbohydrates, undeveloped vascular bundles, and a reduction in glume size during the panicle-initiation stage, while a shortened grain-filling duration, reduced grain-filling rate, and decreased grain width contribute to reduced grain weight during the grain-filling stage. Thus, screening and breeding rice varieties that have comprehensive tolerance to heat stress at all time points during their reproductive stage may be possible to withstand unpredictable heat events in the future. The responses of yield traits to heat stress are regulated by phytohormone levels, which are determined by phytohormone homeostasis. Currently, the biosynthesis and transport of phytohormones are the key processes that determine phytohormone levels in and grain yield of rice under heat stress. Studies on phytohormone homeostatic responses are needed to further reveal the key processes that determine phytohormone levels under heat conditions.

A 4‐year study of the proportional distribution of male reproductive organ abnormalities in cattle slaughtered at Nyagatare abattoir, Eastern Rwanda

Male reproductive performance has more impact on overall herd productivity than in the female. In order to assess herd productivity in cattle in Nyagatare, Eastern Rwanda, the proportional distribution of male reproductive organ abnormalities was investigated in 3087 bulls slaughtered over a 4‐year period. The aim of the study was to investigate the proportional distribution of male reproductive organ abnormalities in exotic and indigenous bulls slaughtered over a 4‐year period at Nyagatare abattoir in Eastern Rwanda. Positioning of the testicles was observed and recorded as the animals were assembled before slaughter. After slaughter, the internal and external reproductive organs of all bulls were removed, labelled and analysed for pathology. Significantly more indigenous (79.01%) than exotic (20.99%) animals were slaughtered (P < 0.05; N = 3 087). Overall occurrence of abnormalities was significantly higher in exotic (20.83%) than in indigenous (10.33%) animals (P < 0.05). Overall, abnormal location of testicles was the most common abnormality (4.08%) followed by abnormal prepuce and penis (2.33%), orchitis (1.94%), enlarged vesicular gland (0.91%), scrotal hernia (0.87%), unilateral cryptorchidism (0.81%), testicular hypoplasia (0.81%) and hydrocoele (0.78%). Abnormal location of testicles, abnormal prepuce and penis, orchitis, testicular hypoplasia and enlarged vesicular glands had significantly higher prevalence in exotic animals than in indigenous animals (P < 0.05). There was no significant difference in the prevalence of unilateral cryptorchidism, hydrocoele and scrotal hernia between the exotic and indigenous breeds. The encountered reproductive abnormalities result in poor herd fertility manifesting as low first‐service conception rates, prolonged breeding seasons and reduced weaning weights accompanied by inevitable financial losses in beef production. The observed high proportion of male reproductive abnormalities in exotic breeds might offset the professed benefits from introduction of these exotic breeds with the aim of improving productivity.

Post-mortem examination of the reproductive organs of female wild boars (Sus scrofa) in Sweden.

In recent decades, wild boars (Sus scrofa) have increased in numbers and distribution in Europe. Compared to other wild ungulates of similar body size, wild boars have a high reproductive capacity. To increase the knowledge of wild boar reproduction, the objective of this study was to investigate characteristics of reproductive organs, and to provide information on the occurrence of abnormalities in reproductive organs from free-ranging female wild boars. Between December 2011 and December 2015, reproductive organs from female wild boars (>30kg body weight), were collected during hunting in four Swedish counties at estates where supplementary feeding was applied. The organs were macroscopically examined and measured. The stage of the reproductive cycle was defined according to the ovarian structures and in relation to uterus characteristics. Observed abnormalities were noted. The results from 569 animals that met the requirements to be included in this study showed significant differences in weight and length of the uterus between the various reproductive stages. Sampling region had significant effect on these differences. Abnormalities in the reproductive organs were present in approximately 10% of the examined animals. The prevalence of abnormalities increased significantly with age and was significantly affected by sampling region.

Bisphenol A Exposure Alters Developmental Gene Expression in the Fetal Rhesus Macaque Uterus

Bisphenol A (BPA) exposure results in numerous developmental and functional abnormalities in reproductive organs in rodent models, but limited data are available regarding BPA effects in the primate uterus. To determine if maternal oral BPA exposure affects fetal uterine development in a non-human primate model, pregnant rhesus macaques carrying female fetuses were exposed orally to 400 µg/kg BPA or vehicle control daily from gestation day (GD) 50–100 or GD100–165. Fetal uteri were collected at the completion of treatment (GD100 or GD165); tissue histology, cell proliferation, and expression of estrogen receptor alpha (ERα) and progesterone receptor (PR) were compared to that of controls. Gene expression analysis was conducted using rhesus macaque microarrays. There were no significant differences in histology or in the percentage of cells expressing the proliferation marker Ki-67, ERα, or PR in BPA-exposed uteri compared to controls at GD100 or GD165. Minimal differences in gene expression were observed between BPA-exposed and control GD100 uteri. However, at GD165, BPA-exposed uteri had significant differences in gene expression compared to controls. Several of the altered genes, including HOXA13, WNT4, and WNT5A, are critical for reproductive organ development and/or adult function. We conclude that second or third trimester BPA exposure does not significantly affect fetal uterus development based on morphological, proliferation, and steroid hormone receptor assessments. However, differences in expression of key developmental genes after third trimester exposure suggest that BPA could alter transcriptional signals influencing uterine function later in life.

Effects of Alternate Treatment of Estrogen Receptor Antagonist and Agonist on Morphology of Male Reproductive Organs of Adult Mice

ICI 182,780 (ICI) is known as an estrogen receptor antagonist, whereas propyl pyrazole triol (PPT) is an estrogen receptor agonist. In this study, ICI or ICI added with PPT was injected into adult male mice. Body and reproductive organ weights were reduced in the ICI added with PPT group compared to the control group. Further, the ICI and ICI added with PPT groups both showed increases in luminal areas of the seminiferous tubules of the testis, whereas cell heights of efferent ductules and the initial segment of the epididymis were reduced. Sperm count in the caudal epididymis was reduced in the ICI and ICI added with PPT groups. These results show that reproductive tissues were more deeply affected in the ICI added with PPT group. We also demonstrated that treatment with ICI resulted in histological changes in the testis, efferent ductule, and epididymis. Further, alternate treatment with ICI and PPT induced abnormalities in reproductive organs. These results indicate that a high concentration of PPT together with ICI may cause histological abnormalities instead of histological restoration in reproductive organs.

Assessment of Abnormalities in Reproductive Organs of Hot Pepper Induced by Low Night Temperature

Low night temperature (LNT) adversely affects productivity of pepper (Capsicum annuum L.) grown in unheated greenhouses. Flower abnormalities were investigated in the local hot pepper cvs. Beldi and Baklouti grown in a growth chamber at a day/night temperature regime of low (25/10°C, LNT) or optimum night temperature (ONT; 25/20°C, as a control). The LNT induced abnormalities in pepper flowers but sensitivity was cultivar dependent; increased ovary diameter in ‘Baklouti’ (40% more than that in ‘Beldi’) was associated with a decrease in style length. Numbers of ovules decreased more than 60% under LNT (more so in ‘Baklouti’). In addition, longitudinal lengths and transverse diameters of ovaries, measured by transverse section, were affected by cultivar and temperature regime. Fruit set percentage was lowest and fruit characteristics were poorest when flowers were self-pollinated under LNT, although artificial pollination with pollen from ONT increased fruit set. More seed per fruit, and heavier and longer fruit, occurred when flowers were pollinated with pollen from ONT than when pollen from LNT was used. Where LNTs have negatively influenced yield, pepper growers need to consider alternative growth and production strategies to reduce damage to flowers.

Molecular mechanisms of induction of persistent changes by estrogenic chemicals on female reproductive tracts and external genitalia

The effects of environmental endocrine-disrupting chemicals (EDCs) are a great and growing concern for human and animal development and life. The reproductive organs are considered as a primary target of EDCs, yet the effects on reproductive organs can extend to other body systems. Perinatal diethylstilbestrol (DES)-exposed mice exhibit various reproductive organ abnormalities. The perinatal DES-exposure model has allowed insight into our understanding of the mechanisms of persistent reproductive organ abnormalities elicited by exposure to estrogens and/or estrogenic EDCs. The persistent changes in the vagina of neonatally DES-exposed mice result from sustained expression of growth factors by ligand-independent transcriptional activation of the estrogen receptor. Developmental regulatory genes, such as Wnt and Hox genes, are also targets of DES during fetal stages and altered gene expression can induce malformations of the reproductive organs. In this review, we focus on the development of female reproductive tracts and external genitalia, and discuss the recent progress in understanding the disruptive effects of estrogens and EDCs on these organs.

Study of smell and reproductive organs in a mouse model for CHARGE syndrome

CHARGE syndrome is a multiple congenital anomaly syndrome characterised by Coloboma, Heart defects, Atresia of choanae, Retardation of growth and/or development, Genital hypoplasia, and Ear anomalies often associated with deafness. It is caused by heterozygous mutations in the CHD7 gene and shows a highly variable phenotype. Anosmia and hypogonadotropic hypogonadism occur in the majority of the CHARGE patients, but the underlying pathogenesis is unknown. Therefore, we studied the ability to smell and aspects of the reproductive system (reproductive performance, gonadotropin-releasing hormone (GnRH) neurons and anatomy of testes and uteri) in a mouse model for CHARGE syndrome, the whirligig mouse (Chd7Whi/+). We showed that Chromodomain Helicase DNA-binding protein 7 (Chd7) is expressed in brain areas involved in olfaction and reproduction during embryonic development. We observed poorer performance in the smell test in adult Chd7Whi/+ mice, secondary either to olfactory dysfunction or to balance disturbances. Olfactory bulb and reproductive organ abnormalities were observed in a proportion of Chd7Whi/+ mice. Hypothalamic GnRH neurons were slightly reduced in Chd7Whi/+ females and reproductive performance was slightly less in Chd7Whi/+ mice. This study shows that the penetrance of anosmia and hypogonadotropic hypogonadism is lower in Chd7Whi/+ mice than in CHARGE patients. Interestingly, many phenotypic features of the Chd7 mutation showed incomplete penetrance in our model mice, despite the use of inbred, genetically identical mice. This supports the theory that the extreme variability of the CHARGE phenotype in both humans and mice might be attributed to variations in the fetal microenvironment or to purely stochastic events.

The common reed in the Chernobyl accident Exclusion Zone: morphometric, cytogenetic and parasitologic studies

The main purposes of our research were to assess the abnormality rate of common reed’s reproductive organs to reveal possible morphological changes, to evaluate the chromosome aberration rate in root meristems and to analyse the morbidity of plants by the ergot (Claviceps purpurea) and by gall-producing arthropods in water bodies with different levels of radioactive contamination within the Chernobyl accident Exclusion Zone. The main water bodies were Glubokoye Lake and Dalekoye-1 Lake, Azbuchin Lake and Yanovsky Crawl, cooling pond of the Chernobyl NPP as well as Pripyat River and Uzh River. Average absorbed dose rate was found from 0.022 to 0.120 Gy/year for the reed from littoral and sublittoral zone of investigated water bodies: Chernobyl NPP cooling pond (0.022); Yanovsky Crawl (0.037); Azbuchin Lake (0.046); Dalekoe-1 Lake (0.053) and Glubokoe Lake (0.120). The highest rate of the absorbed dose was found for the lakes of the left-bank dammed floodplain of the Pripyat River (Dalekoe and Glubokoye), which are the most radioactive contaminated territory within the Exclusion Zone. Performed studies indicate the existence of authentic morphometric and morphological abnormalities of reproductive organs of the common reed. The most typical abnormalities are decreasing of average reed panicle length and width, decreasing of the number of flowers of a low-level blossom cluster and also modification of the shape and colour of the seeds in comparison with standard parameters for the common reed of Europe’s middle latitude. The highest chromosome aberrations rate in root meristems of the common reed (17.8-10.8 %) were registered in plants from lakes within the left-bank flood lands of the Pripyat River, the lowest one (4.5-2.2 %) - in plants from the Pripyat River and Uzh River. The high level of parasitic fungi (Claviceps purpurea) and gall-producing arthropods (Steneotarsonemus phragmitidis and S. gibber) lesion in the most contaminated water bodies within the Chernobyl NPP accident exclusion zone was registered. The damage events of common reed by larvae of gall fly of family Chloropidae, genus Lipara has been considered as well. Above mentioned phenomenon may testify upon the decreasing of the parasitical stability of the common reed under impact of long-term radiation exposure.

Relationships between the abnormalities of the male reproductive organs and the accumulation of phenol compounds in the striped field mouse, Apodemus agrarius, inhabiting Korea

The relationships between the abnormalities of the male reproductive organs in striped field mice and the accumulation of endocrine-disrupting chemicals were assessed. Most mice collected at three areas were contaminated with phenol or organotin compounds. Fourteen to 42% of the mice at each area had abnormally shrunken reproductive organs, and some of them were contaminated with high levels of phenol compounds. Moreover, all the shrunken reproductive organs were damaged in the histological structure. The damage was observed also from several mice accumulating a high level of phenol compounds even though they had normally developed reproductive organs, although no damage was found in the mice accumulating a high level of organotin compounds. Collectively, the abnormalities of the reproductive organs in the mice seemed to be related to the accumulation of phenol compounds rather than of organotin compounds.

Neonatal Exposure to Diethylstilbestrol Alters the Expression of DNA Methyltransferases and Methylation of Genomic DNA in the Epididymis of Mice

Fetal and neonatal exposure to diethylstilbestrol (DES) is known to cause many abnormalities, such as cancer, in the male and female reproductive tracts later in life, and epigenetic mechanisms, such as DNA methylation, may be involved in these processes. In the present study, newborn C57BL/6 male mice were exposed to 3 mug of DES from postnatal days 1 to 5. Subsequently, the expression levels of the DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b and the transcription factors Sp1 and Sp3, which have been reported to regulate the expression of Dnmts, were examined at days 5, 14 and 30. Furthermore, restriction landmark genomic scanning (RLGS), which can analyze genome-wide DNA methylation, was performed to clarify whether or not aberrant DNA methylation was present in the epididymis of the DES-treated mice at day 30. Increased expression of Dnmt3b was observed at days 5 and 14, followed by increased expression of Dnmt1 and Dnmt3a at day 30, as evaluated by real-time RT-PCR. The expression of Sp1 was also increased at day 30. The RLGS analysis revealed that 7 loci of the genomic DNA were demethylated and 1 locus was methylated in the epididymis of the DES-treated mice. Four of these loci specifically demethylated in DES-treated mice were cloned, and all were found to be located within CpG islands near genes. In conclusion, our results indicated the possibility that DES-induced abnormalities of reproductive organs are associated with altered expression levels of DNA methyltransferases and DNA methylation.

Prenatal developmental toxicity studies of 1,1,1‐trichloro‐2,2‐bis(4‐methoxyphenyl)ethane (methoxychlor) in rats and rabbits

ABSTRACT The studies were conducted in rats and rabbits to elucidate the potential developmental toxicity of methoxychlor in general accordance with the improved Japanese MAFF guidelines (12‐Nousan‐No. 8147, 2–1–18, 2000). Methoxychlor dissolved in corn oil was administered orally to pregnant Jcl:SD rats on gestational days (GD) 6–19 at a dose of 0,1,50, or 150 mg/kg/day and to pregnant Kbl:JW rabbits on GD 6–27 at a dose of 0,1, 15, or 45 mg/kg/day. Maternal animals were killed on the day after the last day of administration for morphological examination of their fetuses with special attention to the reproductive organs.Adverse effects on maternal animals were found at 2 higher doses in both species; i.e. vaginal red discharge (rat only), abortion or premature delivery (rabbit only), and significantly decreased body weight gains and food consumption. While the numbers of corpora lutea and implants were comparable between the control and treated groups in both species, slight increase in the percent resorptions and fetal deaths in rats and a reduction of fetal weights in both species were observed at the highest dose. Anogenital distance and testicular histology were not affected in rats. Although fetal examination revealed significant increase in the incidences of 27 presacral vertebrae at 2 higher doses in rabbits, there was no treatment‐related increase in the incidence of malformations in rats and rabbits.Based on these results, it is concluded that methoxychlor causes no malformations, including male reproductive organ abnormalities, in either rats or rabbits, although it results in decreased fetal weights and an increased incidence of fetal resorptions or skeletal variations at maternally toxic doses.

Prenatal developmental toxicity studies of 1,1,1‐trichloro‐2,2‐bis(4‐chlorophenyl)ethane (p, p‘‐DDT) in rats and rabbits

ABSTRACT The studies were conducted in rats and rabbits to elucidate the potential developmental toxicity of p, p'‐DDT in general accordance with the improved Japanese MAFF guidelines (12‐Nousan‐No. 8147,2–1–18, 2000). p, p'‐DDT suspended in 1% aqueous solution of CMC was administered orally to pregnant Jcl:SD rats on gestational days (GD) 6–19 at a dose of 0,5, 25, or 100 mg/kg/day and to pregnant KbI: JW rabbits on GD 6–27 at a dose of 0,5,20, or 80 mg/kg/day. Maternal animals were killed on the day after the last day of administration for morphological examination of their fetuses with special attention to the reproductive organs.Adverse effects on maternal animals were found only at the highest dose in both species; i.e., clonic convulsion (2/24 in rats, 5/22 in rabbits), mortality (1/24 in rats), abortion or premature delivery (4/22 in rabbits), and reduced body weight gains and food consumption. However, the control and treated groups showed comparable values for the numbers of corpora lutea and implants, percent preimplantation losses, number of live fetuses, percent resorptions and fetal deaths, sex ratio, fetal body weights, and placental weights in both species, and anogenital distance and testicular histology in rats. Although fetal examination revealed slightly increased incidence of 27 presacral vertebrae in the highest dose group in rats, there was no treatment‐related increase in the incidence of malformations in any of the species.Based on these results, it is concluded that p, p'‐DDT causes no malformations, including male reproductive organ abnormalities, in either rats or rabbits, although it results in an increased incidence of skeletal variations in rats at a maternally toxic dose.

The Development of Male Reproductive Organ Abnormalities After Neonatal Exposure to Tamoxifen Is Genetically Determined

Responses of the male reproductive organs to neonatal exposures of tamoxifen (Tx) were examined in seven different strains of mice (A/J, AKR/J, BALB/cAnN, C3H/HeJ, C57BL/6J, DBA/ 2J, and FVB/N). Male mice were given daily subcutaneous injections of 2 microg Tx from postnatal day 1 to 5, and the testes, epididymides, ductus deferens, and seminal vesicles were examined at 3 months of age. At necropsy, the testes and seminal vesicles of Tx-treated groups were significantly smaller in size than those of the control groups in all strains. Histologically, the testes of AKR/J, BALB/cAnN, and FVB/N mice showed no abnormality after neonatal treatment with Tx. In contrast, the testes of A/J, C3H/HeJ, C57BL/6J, and DBA/ 2J mice were often necrotic and highly disorganized, with severe inflammation. In the connective tissue surrounding these testes, relatively large arteries were involved in the inflammation, and the vascular lumen was occluded by the thickened tunica interna, suggesting that these testicular changes were due to infarction. Similarly, the epididymides and ductus deferens of Tx-treated A/J, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/N mice showed chronic pyogranulomatous inflammation. The epithelium of the seminal vesicles of Tx-treated A/J, C3H/HeJ, C57BU6J, DBA/2J, and FVB/N mice also exhibited moderate hyperplasia, with squamous metaplasia. These results indicate that neonatal exposure to Tx causes various abnormalities of the male reproductive organs in postpubertal mice, depending on the strains, and suggest that a genetic component plays a major role in determining the phenotypic variation observed.

Reproductive function in rats exposed neonatally to bisphenol A and estradiol benzoate

The reproductive function in rats treated subcutaneously (s.c.) with 300 μg/g bisphenol A or 2 μg/g estradiol benzoate from postnatal Day 1 to 5 was examined after puberty as well as histolopathogic changes in reproductive organs. All male and female rats treated postnatally with estradiol benzoate showed poor reproductive capability, including adverse effects on masculine sexual behavior, and marked histopathologic alterations of the reproductive organs. In addition, estradiol benzoate markedly reduced the volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in males. On the other hand, all male and female rats treated postnatally with bisphenol A showed normal reproductive function and no histopathologic abnormalities of reproductive organs. Bisphenol A did not affect the volume of the SDN-POA. These results indicated that neonatal exposure to estradiol benzoate affects reproductive function in male and female rats, and treatment with bisphenol A at a fairly high dose was ineffective if given postnatally to male and female rats.

Cellular Effects of Early Exposure to Sex Hormones and Antihormones

Publisher Summary This chapter describes the genital effects of perinatal exposure to sex hormones and the induction of nongenital abnormalities, with special emphasis on the cellular basis for the changes observed. Sex hormones and related compounds are potent molecules, which can induce a wide variety of abnormalities in male and female mice when given during the critical developmental period of genital and nongenital target organs. Perinatal treatment of female mice with sex hormones, especially natural and synthetic estrogens and phytoestrogens, causes abnormalities in reproductive organs: estrogen-dependent or estrogen-independent persistent proliferation and cornification of vaginal epithelium, adenosis, oviducal hypertrophy, uterine metaplasia, hypospadias, aplasia of uterine glands, disorganization of uterine myometrium, and infertility resulting from alterations of the hypothalamohypophyseal-ovarian axis. In male mice perinatal treatment with estrogens and androgens induces persistent suppression of spermatogenesis, atrophy of seminal vesicle and prostate, and gubernaculum degeneration resulting in cryptorchidism. In addition to these abnormalities in reproductive organs, perinatal treatment with sex hormones affects the development of bones such as those of the pelvis. The shape of the ischium is transformed to the male type under the influence of early postnatal androgen.