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Research Question: Is anogenital distance (AGD) a useful clinical tool for predicting polycystic ovarian syndrome (PCOS) and its main National Institutes of Health (NIH) phenotypes?, Design: Case-control study conducted between September 2014 and May 2016 at the Department of Obstetrics and Gynecology of the University Clinical Hospital 'Virgen de la Arrixaca' in the Murcia region (south-eastern Spain). One hundred and twenty-six cases of PCOS and 159 controls without PCOS were included. AGD measurements were taken from the anterior clitoral surface to the upper verge of the anus (AGD AC ), and from the posterior fourchette to the upper verge of the anus (AGD AF ). Parametric and non-parametric tests and receiver operating characteristic (ROC) curves were used to assess associations between AGD and the presence of PCOS and its phenotypes., Results: AGD AC , but not AGD AF , was associated with PCOS and all its phenotypes (P-values < 0.001 to 0.048). The highest area under the curve (0.62; 95% confidence interval 0.55 to 0.71) was obtained for all PCOS with AGD AC with a sensitivity and specificity of 50.0% and 73.0%, and positive and negative predictive value of 59.0% and 64.4%, respectively., Conclusions: AGD AC could moderately discriminate the presence of PCOS and may be a useful clinical tool., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The yellow fever mosquito, Aedes aegypti, has three genes that code for proteins with sequence similarity to vertebrate Na + -K + -Cl - cotransporters (NKCCs) of the solute-linked carrier 12 superfamily of cation-chloride cotransporters (CCCs). We hypothesized that these mosquito NKCC orthologues have diverged to perform distinct roles in salt secretion and absorption. In phylogenetic analyses, one protein (aeNKCC1) groups with a Drosophila melanogaster NKCC that mediates salt secretion whereas two others (aeCCC2 and aeCCC3) group with a Drosophila transporter that is not functionally characterized. The aeCCC2 and aeCCC3 genes probably result from a tandem gene duplication in the mosquito lineage; they have similar exon structures and are consecutive in genomic DNA. Predicted aeCCC2 and aeCCC3 proteins differ from aeNKCC1 and vertebrate NKCCs in residues from the third transmembrane domain known to influence ion and inhibitor binding. Quantitative PCR revealed that aeNKCC1 and aeCCC2 were approximately equally expressed in larvae and adults, whereas aeCCC3 was approximately 100-fold more abundant in larvae than in adults. In larval tissues, aeCCC2 was approximately 2-fold more abundant in Malpighian tubules compared to anal papillae. In contrast, aeCCC3 was nearly 100-fold more abundant in larval anal papillae compared to Malpighian tubules, suggesting a role in absorption. Western blots with polyclonal antibodies against isoform-specific peptides revealed stronger aeCCC2 immunoreactivity in adults versus larvae, whereas aeCCC3 immunoreactivity was stronger in larvae versus adults. The differential expression pattern of aeCCC2 and aeCCC3, and their sequence divergence in transmembrane domains, suggests that they may have different roles in transepithelial salt transport., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Dietary phytoestrogens may prevent certain human diseases, but endocrine activity has been reported in animal studies. Sprague-Dawley rats were exposed perinatally to a 1-, 10- or 100-fold "high human dietary intake" mixture of 12 phytoestrogens consisting of mainly the lignan secoisolarici resinol and the isoflavones genistein and daidzein. This mixture induced persistent adverse effects, as adult male mammary glands showed hypertrophic growth. A reduced anogenital distance in newborn males indicated an anti-androgenic mode of action. Testosterone levels, testis and prostate weights, and expression of selected genes in testis and prostate were unaffected. Decreased serum estradiol was seen in genistein-exposed dams. This study indicated adverse effects at high intake levels in rats, but does not provide evidence for risk of phytoestrogen-mediated endocrine disruption at normal human dietary consumption levels. Further studies are warranted to increase the knowledge upon which risk assessment on dietary phytoestrogen exposure during pregnancy and infancy is based., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In animal models, prenatal stress programs reproductive development in the resulting offspring, however little is known about effects in humans. Anogenital distance (AGD) is a commonly used, sexually dimorphic biomarker of prenatal androgen exposure in many species. In rodents, prenatally stressed males have shorter AGD than controls (suggesting lower prenatal androgen exposure), whereas prenatally stressed females have longer AGD than controls (suggesting greater prenatal androgen exposure). Our objective was to investigate the relationship between stressful life events in pregnancy and infant AGD. In a prospective cohort study, pregnant women and their partners reported exposure to stressful life events during pregnancy. Pregnancies in which the couple reported 4+ life events were considered highly stressed. After birth (average 16.5 months), trained examiners measured AGD in the infants (137 males, 136 females). After adjusting for age, body size and other covariates, females born to couples reporting high stress had significantly longer (i.e. more masculine) AGD than females born to couples reporting low stress (p=0.015). Among males, high stress was weakly, but not significantly, associated with shorter AGD. Our results suggest prenatal stress may masculinize some aspects of female reproductive development in humans. More sensitive measures of prenatal stress and additional measures of reproductive development are needed to better understand these relationships and clarify mechanisms., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In humans, recent studies have correlated anogenital distance (AGD) in adult men to intrinsic testicular function. Although rodent studies suggest that AGD is determined in utero and remains constant in adult life, it is not certain if AGD remains constant across a man's adult life. We sought to determine if adult male AGD varies based on age. A cross-sectional study of men being evaluated at a men's health clinic. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length (PL) were measured using digital callipers. anova and linear regression were used to determine correlations between AGD, fatherhood status and age. In all, 473 men were included in the analysis with a mean age of 43 ± 13 years. The mean AGD for the group was 39 ± 13 mm. Anogenital distance did not vary between age categories for the entire group, for fathers, and for childless men. Moreover, penile length also remained constant across age categories. On adjusted analyses stratified by fatherhood status, there was no relationship between AGDp and age. The current cross-sectional study demonstrates that anogenital distance, defined as the distance from the posterior scrotum to the anal verge, is similar for men of different ages. As such, AGD may provide a measure for genital development and function throughout adult life. However, confirmation with longitudinal studies is needed., (© 2012 American Society of Andrology and European Academy of Andrology.)

Danforth's short tail (Sd) is a semidominant mutation on mouse chromosome 2, characterized by spinal defects, urogenital defects, and anorectal malformations. However, the gene responsible for the Sd phenotype was unknown. In this study, we identified the molecular basis of the Sd mutation. By positional cloning, we identified the insertion of an early transposon in the Sd candidate locus approximately 12-kb upstream of Ptf1a. We found that insertion of the transposon caused overexpression of three neighboring genes, Gm13344, Gm13336, and Ptf1a, in Sd mutant embryos and that the Sd phenotype was not caused by disruption of an as-yet-unknown gene in the candidate locus. Using multiple knockout and knock-in mouse models, we demonstrated that misexpression of Ptf1a, but not of Gm13344 or Gm13336, in the notochord, hindgut, cloaca, and mesonephros was sufficient to replicate the Sd phenotype. The ectopic expression of Ptf1a in the caudal embryo resulted in attenuated expression of Cdx2 and its downstream target genes T, Wnt3a, and Cyp26a1; we conclude that this is the molecular basis of the Sd phenotype. Analysis of Sd mutant mice will provide insight into the development of the spinal column, anus, and kidney., Competing Interests: The authors have declared that no competing interests exist.

Experimental animal studies show that measurement of anogenital distance (AGD) and/or penis length may provide lifelong 'read-outs' of foetal androgen exposure during the masculinization programming window (MPW). However, variation in postnatal androgen exposure may complicate interpretation of such measurements. This is important to clarify if such measurements are to be applied to humans. The present aim was to evaluate effects of prenatal and/or postnatal manipulation of androgen production/action on growth of AGD and the penis in rats. Pregnant rats were treated daily before (e13.5-e21.5) and after birth (postnatal days 1-15) with either vehicle, 500 mg/kg di(n-butyl) phthalate (DBP) or 100 mg/kg flutamide (postnatal only) in prenatal + postnatal treatment combinations (N = 6 treatment combinations); DBP impairs androgen production whereas flutamide impairs androgen action. Male offspring were killed on postnatal day 8 (prepuberty), 25 (early puberty) or 90 (adulthood) when AGD was measured, the penis dissected out and its weight and length measured; plasma testosterone and ventral prostate weight were measured at day 90 to assess endogenous androgen exposure. In controls, penis length, girth and AGD increased 2.2-, 5.3-and 5.9-fold respectively from day 8 to day 90. Significant inhibition of penis growth and final length and girth was induced by treatments that inhibited postnatal androgen action. Conversely, growth and ultimate (adult) AGD was inhibited by prenatal inhibition of androgen production whereas postnatal androgen inhibition had negligible effect. Nevertheless, AGD and penis length were highly correlated at every age (R(2) > 0.33; p < 0.0001). However, altered endogenous androgen exposure may confound interpretation of changes in adults exposed prenatally/postnatally to DBP/flutamide. We conclude that AGD provides a lifelong guide to prenatal androgen exposure (in the MPW) whereas penis size reflects both prenatal + postnatal androgen exposure. At the group treatment level, prepubertal measurement of either AGD or penis size accurately predicts their size in adulthood., (© 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.)

There is now considerable interest in the intestinally derived soy isoflavone metabolite, equol, which occurs in the enantiomeric forms, S-(-)equol and R-(+)equol, both differing in biological actions. Little is known about effects of either enantiomer on reproductive development, yet such knowledge is fundamental because of the recent commercialization of S-(-)equol as a dietary supplement. S-(-)equol and R-(+)equol were therefore investigated to determine their effects on reproductive development and fertility in the Sprague-Dawley rat. Neither enantiomer affected fertility, number of litters produced, number of pups per litter, number of male and female pups born, birth weight, anogenital distance, testicular descent or vaginal opening. Histological analysis showed no major abnormalities in ovary, testis, prostate or seminal vesicle tissue with dietary exposure to S-(-)equol or R-(+)equol, but both enantiomers triggered hyperplasia of uterine tissue. With R-(+)equol this stimulatory effect subsided after exposure was discontinued, but the effect of S-(-)equol was prolonged., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: In male rodents, anogenital distance (AGD) provides a sensitive and continuous correlate of androgen exposure in the intrauterine environment and predicts later reproductive success. Some endocrine-disrupting chemicals can alter male reproductive tract development, including shortening AGD, in both rodents and humans. Whether AGD is related to semen quality in human is unknown., Objective: We examined associations between AGD and semen parameters in adult males., Methods: We used multiple regression analyses to model the relationships between sperm parameters and two alternative measures of AGD [from the anus to the posterior base of the scrotum (AGD(AS)) and to the cephalad insertion of the penis (AGD(AP))] in 126 volunteers in Rochester, New York., Results: AGD(AS), but not AGD(AP), was associated with sperm concentration, motility, morphology, total sperm count, and total motile count (p-values, 0.002-0.048). Men with AGD(AS) below (vs. above) the median were 7.3 times more likely (95% confidence interval, 2.5-21.6) to have a low sperm concentration (< 20 × 10⁶/mL). For a typical study participant, sperm concentrations were 34.7 × 10⁶/mL and 51.6 × 10⁶/mL at the 25th and 75th percentiles of (adjusted) AGD(AS)., Conclusions: In our population, AGD(AS) was a strong correlate of all semen parameters and a predictor of low sperm concentration. In animals, male AGD at birth reflects androgen levels during the masculinization programming window and predicts adult AGD and reproductive function. Our results suggest, therefore, that the androgenic environment during early fetal life exerts a fundamental influence on both AGD and adult sperm counts in humans, as demonstrated in rodents.

Purpose: Our laboratory has developed and implanted a novel bioengineered internal anal sphincter (IAS) to treat anal incontinence. Fibroblast growth factor-2 (FGF-2) has been used in mice; however, the optimal growth factor for successful IAS implantation is unclear. This study compares several growth factors in order to optimize IAS viability and functionality., Methods: Bioengineered IAS rings were implanted subcutaneously into the dorsum of wildtype C57Bl/6 mice, with an osmotic pump dispensing FGF-2, vascular endothelial growth factor (VEGF), or platelet-derived growth factor (PDGF) (n = 4 per group). Control mice received IAS implants but no growth factor. The IAS was harvested approximately 25 days post-implantation. Tissue was subjected to physiologic testing, then histologically analyzed. Muscle phenotype was confirmed by immunofluorescence., Results: All implants supplemented with growth factors maintained smooth muscle phenotype. Histological scores, blood vessel density and muscle fiber thickness were all markedly better with growth factors. Neovascularization was comparable between the three growth factors. Basal tonic force of the constructs was highest with VEGF or PDGF., Conclusion: All growth factors demonstrated excellent performance. As our ultimate goal is clinical implantation, our strong results with PDGF, a drug approved for use in the United States and the European Union, pave the way for translating bioengineered IAS implantation to the clinical realm.

Purpose: The epithelial lining of the anorectum still raises discussions concerning the levels of transition between the various zones and leads to an incomplete understanding of the immmunoprofile of rectal carcinoma. Since the expression of cytokeratins depends on the epithelial cell-type and the parahox-gene CDX2 is important for the development of the colorectal epithelium, we investigated different cytokeratins and CDX2 in the anorectum of human prenatal stages and in adult normal and neoplastic anorecta., Materials and Methods: The differentiation and spatiotemporal distribution of the epithelial zones were examined in 33 human embryos and fetuses, in a 2-year-old child and four adults. In comparison, 17 specimens of ultralow rectal adenocarcinoma and 4 specimens of anal carcinoma were investigated. Monoclonal antibodies were directed against cytokeratin (CK) 18, 20, 7 and 14 and CDX2., Results: Due to the cytokeratin profile and to CDX2 expression, the different anorectal zones could already be differentiated in human prenatal life. We showed that anorectal epithelial differentiation including the squamous epithelia ran in a craniocaudal direction, and that the anorectal zone was a transitional zone between rectal zone and anal transitional zone where CK 7, 18, 20 and CDX2 are simultaneously expressed. All cases of rectal adenocarcinoma showed positivity for CK 18, 20 and CDX2, and three also labelled for CK 7, whereas CK 14 was only expressed in the cases of anal carcinoma., Conclusions: Our results elucidate the connection between the prenatal pattern and the origin of the different types of anorectal carcinoma.

Perinatal di(2-ethylhexyl) phthalate (DEHP) exposure was examined in time-mated Wistar rats gavaged from gestation day 7 to postnatal day 16 with doses from 3 to 900 mg/kg-d. These doses covered the whole dose-response curve for the demasculinizing effects of DEHP including low-dose effects. At a relatively low dose of 10 mg/kg-d, DEHP caused adverse anti-androgenic effects on male rat development as male anogenital distance was decreased, the incidence of nipple retention was increased, weight of levator ani/bulbocavernosus muscles and prostate was reduced and mild external genitalia dysgenesis was observed. Higher doses of DEHP induced histopathological effects on the testes, reduced testis weight, and expression of androgen-regulated genes in the prostate. The results provide new evidence of low-dose effects of DEHP and are consistent with the EU NOAEL of 5 mg/kg for DEHP. Our results also indicate a reason for concern about human exposure to DEHP., (Copyright 2010 Elsevier Inc. All rights reserved.)

The aim of this study was to investigate long-term effects of prenatal betamethasone exposure on sexual partner preference, testosterone level, and sexual behavior. Pregnant rats received 0.1 mg/kg of betamethasone or saline on the 12th, 13th, 18th, and 19th days of pregnancy. Parameters in male offspring were evaluated at 90 days of age. Male rats from the betamethasone group did not show any difference in sexual partner preference as expressed by the total number of visits to the female or male zone. However, these males spent significantly less total time and shorter duration per visit in the female zone than their controls. Therefore, prenatal exposure to betamethasone led to a significantly lower sexual female partner preference score compared to the control group. These animals also presented diminished testosterone levels in adulthood. Prenatal exposure to betamethasone induced a delay in the latency to first ejaculation, as well as a decrease in the numbers of postejaculatory intromissions, total intromissions and total ejaculations. Although 80% of the betamethasone-treated animals exhibited male sexual behavior, when they were castrated and pretreated with estrogen, 50% of them showed lordosis and accepted mounts of another sexually experienced male. These results suggest that the prenatal treatment with betamethasone, by increasing maternal corticosteroid level, may have diminished testosterone peak in male pups, a peak crucial to brain sexual differentiation. As a consequence, the prenatal betamethasone treatment reduced the testosterone level in adulthood and altered partner preference and sexual behavior.

Most bilaterian animals possess a through gut with a separate mouth and anus. It is commonly believed that during the transition from radial to bilateral symmetry, both openings evolved simultaneously by the lateral closure of a slit-like blastopore. Molecular phylogenies however, place the acoel flatworms, which have only one opening to their digestive system, as the sister group to all remaining Bilateria. To address how this single body opening is related to the mouth and anus of the protostomes and deuterostomes, we studied the expression of genes involved in bilaterian foregut and hindgut patterning during the development of the acoel Convolutriloba longifissura. Here we show that the genes brachyury and goosecoid are expressed in association with the acoel mouth, suggesting that this single opening is homologous to the mouth of other bilaterians. In addition, we find that the genes caudal, orthopedia and brachyury-which are expressed in various bilaterian hindguts-are expressed in a small region at the posterior end of the animal, separated from the anterior oral brachyury-expressing region by a dorsal domain of ectodermal bmp2/4 expression. These results contradict the hypothesis that the bilaterian mouth and anus evolved simultaneously from a common blastoporal opening, and suggest that a through gut might have evolved independently in different animal lineages.

Purpose: The internal anal sphincter (IAS) plays an important role in the pathophysiology of constipation and incontinence. We hypothesized that functional bowel obstruction in premature infants is because of a poorly developed IAS. We investigated the neuromuscular development of IAS in fetal, newborn, and adolescent pigs., Methods: Paraffin sections of IAS from 5 different age groups, E60, E90, 1 day, 4, and 12 weeks old, were stained with protein gene product 9.5 (PGP9.5), *-smooth muscle actin (*-SMA), caldesmon (CALD), calponin (CALP), and desmin (DES) antibodies. Quantification of results was performed by grading the density of immunostaining., Results: The PGP9.5-positive ganglion cells were observed in the myenteric and submucosal region of the entire length of the IAS at E60. An increase in ganglion cell size and density was observed with increasing age. There were striking differences in the density of PGP9.5, alpha-SMA, DES, CALD, and CALP immunoreactive fibers between prenatal and postnatal period with gradient increase in the number of fibers from after birth to 12 weeks of age., Conclusion: This study shows for the first time that there are age-related differences in the distribution of neurons and smooth muscle cell components in the IAS. The decreased expression of contractile and cytoskeleton proteins in smooth muscle cells together with decreased expression of neurons in the IAS in the perinatal period may lead to motility dysfunction causing functional intestinal obstruction seen in premature infants.

The anorectal canal has two origins; the upper part is derived from endoderm and the lower part is derived from ectoderm. The process of ectodermal contribution to the canal remains unclear. To understand the development of this area, serial sagittal sections of mouse embryos were made every 12h from embryonic day 13.0 (E13.0) to E18.5. Three-dimensional (3-D) reconstructions were obtained from these sections. At the time of the disappearance of the cloacal membrane (E13.5), the endodermal lining reached the site of disintegrated membrane. Thus, the whole canal was of endodermal origin. The transitional zone between the dorsal end of the primary perineum and tail was thicker than other ectodermal epithelia. In this region, it changed from an acute to obtuse angle. After it straightened out and formed the canal, the secondary perineum appeared caudally. During these processes, the external sphincter appeared in the underlying mesenchyme of the thick ectoderm and functioned as a drawstring to form the ectodermal anal canal.

Triazole fungicides associated with a range of reported male reproductive effects in experimental animals were selected to assess potential toxic modes of action. Wistar Han rats were fed myclobutanil (M: 100, 500, or 2000 ppm), propiconazole (P: 100, 500, or 2500 ppm), or triadimefon (T: 100, 500, or 1800 ppm) from gestation day 6 to postnatal day (PND) 120. One male per litter was necropsied on PND1, 22, 50, or 92. Measurements included anogenital distance (AGD) at PND0, body and organ weights, serum hormone levels, age at preputial separation (PPS), sperm morphology and motility, and fertility and fecundity. AGD was increased by the high dose of all three triazoles, indicating hypervirilization. Triadimefon delayed PPS, consistent with delayed puberty, at 1800 ppm. Relative liver weights were increased at PND1, 50, and 92 by all three triazoles. Hepatocellular hypertrophy was present at PND50 from propiconazole and triadimefon and at PND92 from all three high-dose triazole treatments. Relative pituitary weights were decreased at PND92 by middle- and high-dose myclobutanil treatment. Absolute testis weights were increased at PND1 by myclobutanil, at PND22 by myclobutanil and triadimefon, and at PND50 by propiconazole and triadimefon treatment. Relative ventral prostate weights were increased at PND92 by myclobutanil and triadimefon treatment. Serum testosterone was increased at PND50 by triadimefon and at PND92/99 by all three triazole treatments. Insemination and fertility were impaired by myclobutanil and triadimefon treatment. In addition to the reproductive system effects, total serum thyroxine levels were decreased at PND92 by high-dose triadimefon. These reproductive effects are consistent with the disruption of testosterone homeostasis as a key event in the mode of action for triazole-induced reproductive toxicity.

Larvae of endoparasitoids undergo extensive morphological changes and often have special features to allow their development inside the host. We present the first detailed study on the development of the anal vesicle and the gut. The analyses reveal that the anal vesicle is first seen on the dorsal side of the abdomen as an internal structure covered by a membrane. The morphology of the abdomen then changes intensively: new segments are formed and the anal vesicle develops from a crest of large cells to a protrusion. Towards the end of the first instar, the anal vesicle is fully evaginated and no longer covered by a membrane; the large epithelial cells have microvilli on their apical side which suggests uptake of nutrients from the host's haemolymph. When the larva has moulted to the second instar, the ultrastructure of the anal vesicle begins to change and shows signs of degeneration. In this stage the epithelium of the midgut is fully developed and has a brush border which suggests that nutrient uptake occurs now primarily through the midgut. The anal vesicle then degenerates completely. The salivary glands are prominent already in first instar larvae and appear to produce and release a host regulatory 212 kD protein.

Macro-microscopical and histological methods were used to study the age-related peculiarities of human anal glands in 267 practically healthy subjects of both sexes of various ages (from newborns to 102 years). Topography of anal glands was described, their numbers and dimensional parameters were determined in the subjects of different age. Maximal total number of these glands, maximal length and width of their initial region, as well as maximal number of initial portions within it, were found at the age of 22-35 years. Subsequently, as the age increased, these parameters tended to decrease. Connective tissue fiber content in the glands was found to increase during postnatal ontogenesis. Along the course of common excurrent duct in submucosa and in mucosa, some dilated regions were found, especially in aged and senile persons.

Involution of lymphoid tissues in relation to age has not been defined for bottlenose dolphins (Tursiops truncatus). Twenty-five bottlenose dolphins from the coast of Texas and western Louisiana were examined and complete necropsies were performed with histological samples taken of nearly all tissues. Ages ranged from several days to 27 years. The histology of four lymphoid organs-thymus, pharyngeal tonsil, mucosa-associated lymphoid tissue (MALT) of the colon, and anal tonsil-was assessed. Numerical scores were assigned to specific morphological features, thus creating an involution score. Definable and scorable features of each organ were selected for evaluation and determination of loss of lymphoid elements. Neonatal dolphins were recorded as the reference standard for no involution. The highest score for each organ represented the greatest amount of retention of tissue elements. Thus, the lower the score, the greater degree of involution. Comparing involution scores to tooth age permitted an assessment of involution over time. The greatest degree of involution was found in the MALT of the colon. The MALT of the colon declined dramatically so that after age 10 it was absent from 4 of 14 animals and minimally present in 8 others. Thymic tissue also suffered a precipitous drop in volume after about age 5, but was found in animals up to 24 years of age. Involution was moderate and variable in both pharyngeal and anal tonsils. In some animals, these tissues were reduced in volume early, and prominent in others well into adult life (over 20 years)., ((c) 2004 Wiley-Liss, Inc.)

Lines of turkeys selected for rapid growth and high meat yield have an increased incidence of prolapse of the oviduct compared with unselected or traditional strains of turkeys. The development of the reproductive system and changes in plasma estrogen concentrations were compared in sire line and traditional turkeys with the aim of identifying any morphological or hormonal differences that could be associated with the high incidence of prolapse in the male line. Four turkeys from each strain were killed weekly from 0 to 7 wk postphotostimulation, and samples from prolapsed birds were obtained from field cases. There were no differences in the rate of development of the ovary, oviduct, uterus, vagina, sphincter ani muscle, or muscular cord of the ventral ligament between the two strains that could predispose the sire line to prolapse. Histological investigation of the uterus, vagina, muscular cord of the ventral ligament, and sphincter ani muscle 5 wk postphotostimulation in traditional, sire line, and prolapsed sire line turkeys did not reveal any differences that could be associated with prolapse. No prelay peak in plasma estradiol concentration was observed in either strain, and there was no evidence to suggest that plasma estradiol was higher in the sire line compared with the traditional turkeys. It was concluded that prolapse of the oviduct in sire line turkeys was not associated with any anatomical abnormalities or high plasma estradiol during reproductive development.

In Drosophila, the homeotic gene Distal-less (Dll) has a fundamental role in the establishment of the identity of ventral appendages such as the leg and antenna. This study reports the expression pattern of Dll in the genital disc, the requirement of Dll activity for the development of the terminalia and the activation of Dll by the combined action of the morphogenetic signals Wingless (Wg) and Decapentaplegic (Dpp). During the development of the two components of the anal primordium - the hindgut and the analia - only the latter is dependent on Dll and hedgehog (hh) functions. The hindgut is defined by the expression of the homeobox gene even-skipped. The lack of Dll function in the anal primordia transforms the anal tissue into hindgut by the extension of the eve domain. Meanwhile targeted ectopic Dll represses eve expression and hindgut formation. The Dll requirement for the development of both anal plates in males and only for the dorsal anal plate in females, provides further evidence for the previously held idea that the analia arise from two primordia. In addition, evaluation was made of the requirement for the optomotor-blind (omb) gene which, as in the leg and antenna, is located downstream to Dpp. These results suggest that the terminalia show similar behaviour to the leg disc or the antennal part of the eye-antennal disc consistent with both the proposed ventral origin of the genital disc and the evolutive consideration of the terminalia as an ancestral appendage.

To explore the role of androgens in early development on adult hypothalamic-pituitary-adrenal (HPA) function in males, we administered flutamide or vehicle injections: (1) to pregnant dams on embryonic days 15-20; (2) to neonatal pups on days 0-5; or (3) to adults on days 55-60. At approximately 70 days of age, trunk blood was collected to determine corticosterone levels (1) upon removal from the home cage, (2) immediately after 30 min of restraint stress, or (3) 60 min after return to home cage following the stressor. Flutamide treatment resulted in higher basal levels of testosterone and stress levels of corticosterone compared to vehicle treatment, and there was no interaction of treatment with age at time of treatment. This suggests that testosterone is less effective at inhibiting HPA function in flutamide-treated males. In addition, prenatally treated males had higher stress levels of corticosterone than neonatally and adult-treated males, regardless of the type of treatment. There were no differences in CBG levels among the groups. The results suggest that, in males, flutamide treatment has a long-lasting effect on HPA function. These results are consistent with our previous research on neonatally gonadectomized males and the hypothesis of organizational effects of sex hormones on HPA function., (Copyright 1999 Academic Press.)

In twelve Chinese miniature pigs (CMP), of both sexes and ranging from newborn to 5 months of age, the postnatal developmental features of the cleavage lines of the skin of the whole body were examined by the stab-wound method, using a metal probe with a sharp conical point. 1). The CL patterns of the skin in the 5-month-old CMP were largely similar to those of adult Landrace-strain pigs (Wakuri et al., 1993). 2). At each monthly stage, the CL of the skin of the inter-ocular area, medial ocular angle, umbilicus, preputial orifice and anus presented a convergent arrangement. An annular pattern was found in the skin around the eye, the base of the ear, and the vulva. 3). Some alterations in CL patterns were seen during the general and regional growth of CMP, as shown in the skin of the lateral side of the trunk, the prepuce and the scrotum.

By means of complex histological and injection methods, including roentgenovasography and morphometry, 140 preparations of the human rectum have been studied during the late and middle fetal period, as well as during all periods of the postnatal ontogenesis. On the lateral walls of the columnar zone of the anal canal, places where the internal haemorrhagic nodes occur especially often, peculiar incapsulated and nonincapsulated microglomal cavernous bodies have been revealed. A large vascular peduncle connects them with the superior rectal artery and vein (according to 2-4 and 8-10 o'clock on the clock face) as complexes consisting of 2-3 penicilli and glomeruli. They are connected with the portocaval anastomoses of the initial multicanal anal-columnar sources of the superior and inferior rectal veins. The latter have various obturative mechanisms represented as microvalves, subintimal muscular toruli and arteriol-venular shunts of the obturative glomal and combined type.

The development of the anorectum was studied in forty-four embryos and foetuses of pig varying in length from 9 mm total length to 210 mm crownrump length and in three newborn pigs. The presence of some features during critical stages in the development of the cloaca in the pig such as an epithelial mass protruding into the dorsal cloaca near its intestinal orifice and distinct differences in the type of epithelium in different regions of the cloacal system greatly facilitated the study of the developmental process. Thus it could be established that a change in position of the dorsal cloaca and adjacent structures such as the distal part of the gut and the urorectal septum via the dorsal part of the cloacal plate towards the tailgroove is of major importance for the partition of the cloaca into a separate intestinal and urogenital division. A subsequent disintegration of the dorsal part of the cloacal plate results in two separate openings for both the systems at the same time. Disintegration of the ventral part of the cloacal plate leads only to a further widening of the external opening of the urogenital system. In the cloacal system three distinct zones were discerned, a dorsal and ventral cloacal and a cloacal plate region. From the dorsal cloacal epithelium the whole anorectal segment between the intestinal mucosa and the anal epidermis develops. The epithelium of ventral cloacal origin seems to disappear completely . Cloacal plate epithelium forms the epithelial lining of distal parts of the urogenital system. The penile urethra in the male is formed by a ventralward movement of the urogenital opening by the growing perineum and not by fusion of genital folds.

In EMG recordings of the external anal sphincter there is a brief contraction in response to rapid rectal distension, and a preserved or increased activity during a prolonged substantial rectal distension in healthy adults. In order to determine if this activity develops during childhood 30 healthy children, aged 2 months to 15 years, were examined with their parents' consent. EMG of the external anal sphincter during rest and during rectal distension was performed. All those children who had gained voluntary anal control showed an EMG recording similar to the adults. The 10 youngest children who had not gained voluntary control showed another EMG pattern. Instead of a brief contraction they had a brief loss of activity in response to rectal distension. During a prolonged rectal distension the external sphincter activity decreased and finally ceased. An intermediate state was found in the two youngest children who had gained voluntary control. The EMG pattern showed a good correlation with the maturation and gain of voluntary control of defaecation.

To investigate the exact nature of anorectal continence, a manometric evaluation was performed in 88 healthy test persons with a two-balloon catheter. The pressure in the anal canal (PAC) and the rectal ampulla at rest (PAR), the maximum squeeze pressure (PAC max) and pressure rise in the anal canal after dilatation of the rectal ampulla delta PAC) were evaluated separately for men and women, and the test persons were divided into 3 age groups (group I: under 40 years, group II: 40-60 years, group III: over 60 years). PAC showed a statistically significant difference between men and women and a constant decrease with age--statistically significant for men and for women between groups II and III--whereas the statistical significance of the 3 other values had to be restricted to a constant decrease with advance in years. Anorectal continence is characterized by a PAC at rest of over 40 mm Hg, a PAC max reaching at least 80 mm Hg, a pressure gradient between rectal ampulla and anal canal of over 20 mm Hg and a delta PAC of more than 10 mm Hg. These values as well as the differences depending on age and sex should be kept in mind for the evaluation of the continence function.