Levels of testosterone, progesterone and oestradiol in pregnant-lactating does in relation to aggression during group housing

The neuroendocrine regulation of rabbit maternal behaviour has been explored in detail. However, little is yet known about the hormonal regulation of aggression in concurrently pregnant-lactating does, a reproductive condition that prevails during group housing of rabbits on farms. Therefore, in this study we determined the relation between a) the levels of progesterone, testosterone, and oestradiol during lactation; b) the anogenital distance at artificial insemination; and c) the timing of grouping with the intensity of agonistic behaviour, published previously. We performed four consecutive trials, where three groups of eight does each were artificially inseminated on day 10 postpartum (pp) and grouped on either day 12, 18 or 22 pp. Using Dipetalogaster maxima, a reduviid blood-sucking bug, we collected blood samples during the pregnant-lactating phase (days 13, 15, 17, 19, 21, 23 pp) on one or two randomly chosen does per treatment group. Testosterone levels varied little across the pregnant-lactating phase, agreeing with results from pregnant-only rabbits, while progesterone levels increased from day 3 (=13 dpp) to day 7 (=17 dpp) and remained unchanged until day 13 (=23 dpp) of pregnancy. All oestradiol concentrations fell below the limit of detection. Overall, all concentrations were slightly lower in comparison to rabbit studies with pregnantonly does. The agonistic behaviour was not related to the respective hormonal concentrations at grouping. In conclusion, the time point of grouping does after artificial insemination (AI) in the semi-group housing system only had a weak influence on aggression and the hormonal profile did not indicate an optimum time for grouping.

Melatonin Ameliorates Developmental Landmarks Induced by Gestational and Lactational Coexposure to Chlorpyriphos and Cypermethrin in F1 Male Rats

The ameliorative potentials of melatonin (ML) on developmental changes evoked by gestational and lactational co-exposure to chlorpyriphos (CP) and cypermethrin (CY) was investigated in male Wistar rats. Pregnant dams were divided at random into 6 groups of 10 animals each and treated orally by gavage from gestation day 1 to postnatal day 21 with the following regimens: The DW, SO and ML groups were administered distilled water (2 ml/kg), soya oil (2 ml/kg) and melatonin (0.5 mg/kg), respectively; CC group was co-administered CP (1.9 mg/kg) and CY (7.5 mg/kg); MC group was pretreated with ML (0.5 mg/kg) and followed by co-administration of CP and CY while the CM group was administered CP and CY and then treated with ML. We evaluated the developmental parameters on the F1 generation male rats at different postnatal intervals following parturition. Alterations in litter size and weight, number of live/dead pups, anogenital distance, crown-rump length, time of eye and ear openings, and testicular descent induced by gestational and lactational exposure to CP and CY in F1 male rats were mitigated by pre- and post-administration of ML. These curative and prophylactic potentials of ML may be partly attributed to its widely known antioxidant property.

Predictors of successful outcome of tubularized incised plate for primary distal hypospadias repair

Background Several preoperative factors affect the outcome of Tabularized Incised Plate (TIP) repair. Our aim was to collect and analyze all these factors to define what the most important predictive factors are. Methods Hundred patients (1–5 years old) with primary distal hypospadias were included. Exclusion criteria included previous penile operations and hormonal treatment or associated congenital anomalies. Anogenital distance (AGD), stretched penile length (SPL), meatal site, glanular shape, chordee and torsion degree, plate width and glans meatus shaft (GMS) score were assessed. TIP repair was done to all patients and followed up for one year. The outcome was correlated with the above parameters. Results Mean ± SD of age of patients was 3.5 ± 1.5 years, while weight was 14.1 ± 3.0 kg. Complication rate was 18% including urethrocutaneous fistula (UCF) and meatal stenosis 14%, repair breakdown 1% and urethral stricture 3%. Patients with chordee degree < 30° and distal penile meatal location were associated with increased risk for complications by 11.6 and 8.2 times; 95% CI was (1.46–91.75) and (1.02–66.52), respectively (p < 0.05 for each). Plate width ≥ 9 mm, AGD > 5 cm, GMS score ≤ 7 (p < 0.001 for each), age of patient ≤ 2 years old, and SPL > 3.5 cm (p < 0.01 for each) were associated with successful outcome of repair. Conclusion The proposed successful criteria of TIP repair were absent chordee, coronal/subcoronal penile meatal location, plate width ≥ 9 mm, AGD > 5 cm, age of patient ≤ 2 years old, GMS score ≤ 7, SPL > 3.5 cm and grooved glanular shape.

On the Use and Interpretation of Areola/Nipple Retention as a Biomarker for Anti-androgenic Effects in Rat Toxicity Studies

Areola/nipple retention (NR) is an established biomarker for an anti-androgenic mode of action in rat toxicity studies. It is a mandatory measurement under several OECD test guidelines and is typically assessed in combination with anogenital distance (AGD). Both NR and AGD are considered retrospective biomarkers of insufficient androgen signaling during the masculinization programming window in male fetuses. However, there are still aspects concerning NR as a biomarker for endocrine disruption that remains to be clarified. For instance, can NR be regarded a permanent adverse effect? Is it a redundant measurement if AGD is assessed in the same study? Is NR equally sensitive and specific to anti-androgenic chemical substances as a shortening of male AGD? In this review we discuss these and other aspects concerning the use of NR as a biomarker in toxicity studies. We have collected available literature from rat toxicity studies that have reported on NR and synthesized the data in order to draw a clearer picture about the sensitivity and specificity of NR as an effect biomarker for an anti-androgenic mode of action, including comparisons to AGD measurements. We carefully conclude that NR and AGD in rats for the most part display similar sensitivity and specificity, but that there are clear exceptions which support the continued assessment of both endpoints in relevant reproductive toxicity studies. Available literature also support the view that NR in infant male rats signifies a high risk for permanent nipples in adulthood. Finally, the literature suggests that the mechanisms of action leading from a chemical stressor event to either NR or short AGD in male offspring are overlapping with respect to canonical androgen signaling, yet differ with respect to other mechanisms of action.

Effect of anogenital distance on stress urinary incontinence

Background To clarify the effect of anogenital distance (AGD) on stress urinary incontinence (SUI) in female patients. Methods Charts of patients who admitted to urogynecology polyclinic between December 2020 and February 2021 were analyzed retrospectively. The AGD parameters including anogenital distance from the anus to the clitoris (AGDAC), anogenital distance from the anus to the fourchette (AGDAF) and genital hiatus (GH) were measured. To identify effect of ADG parameters on SUI, patients were divided into the two subgroups (patients with SUI and without SUI). Demographic characteristics of patients and perineal anatomy measurement were compared between groups. Results Totally, 256 female patients met study inclusion criteria. In comparison of patients with and without SUI, demonstrated that age, weight, height, and BMI were similar between groups (p = 0.200, p = 0.455, p = 0.131, and p = 0.215, respectively). The AGDAF was measured 22.6 mm in patients with SUI and 25.5 mm in patients without SUI (p = 0.014). In contrast, AGDAC was significantly longer in patients with SUI (81.1 mm vs. 72.2 mm, p = 0.001). Also, GH was significantly longer in patients with SUI (p = 0.016). Multivariate logistic regression analysis revealed that one mm increment in AGDAC and GH, is associated with 1.108- and 1.038-fold time of SUI development risk, respectively (p = 0.001 and p = 0.004). In contrast, decrease in AGDAF is resulted with significantly higher risk for SUI (p = 0.001). Conclusion The present study demonstrated that shorter AGDAF, and longer AGDAC and GH were resulted with significantly higher incidence of SUI. Considering the ease and non-invasiveness of anogenital distance measurement, an important implication of the results of current study is that it is a measurement that can be easily performed during routine gynecological and obstetric examinations as a suitable tool for use in the prediction of women who will develop stress incontinence in the future.

Association Between Neonatal Thyroid Function and Anogenital Distance from Birth to 48 Months of Age

BackgroundEvidence from animal studies has indicated that neonatal thyroid function is vital for the reproductive development. Anogenital distance (AGD), a sensitive biomarker of the fetal hormonal milieu, can be used to predict adult reproductive disorders. However, few human studies have examined the association between neonatal thyroid function and AGD. We aimed to explore their associations in a birth cohort study.MethodsConcentrations of thyroid stimulating hormone (TSH) and thyroid hormones (THs), including total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), and free thyroxine (FT4) were measured in cord plasma in the Shanghai-Minhang Birth Cohort. The offspring AGD (AGDAP [anus–penis] and AGDAS [anus–scrotum] for boys and AGDAC [anus–clitoris] and AGDAF [anus–fourchette] for girls), body weight and anogenital index (AGI = AGD/weight [mm/kg]) were obtained at each follow-up visit. In total, 344 children (194 boys and 150 girls) with cord plasma concentrations of THs and TSH and at least one AGD measurement at birth and at 6, 12, and 48 months of age were included. Multiple linear regression and generalized estimating equation (GEE) models were used to examine the associations of cord plasma concentrations of THs and TSH with AGI.ResultsMultiple linear regression models showed inverse associations of TT4, FT3, and FT4 with female AGI, although statistical significance was only reached at birth, 6 and 48 months of age. These associations were also found in GEE models: higher TT4 and FT4 concentrations were associated with lower AGIAC (TT4: β = -0.27, 95% CI: -0.50, -0.03 for middle vs. lowest tertile; FT4: β = -0.38, 95% CI: -0.61, -0.16 for middle and β = -0.30, 95% CI: -0.55, -0.04 for highest vs. lowest tertile). Besides, girls with the highest tertile of FT3 concentrations had lower AGIAF than those with the lowest tertile (the highest vs. lowest tertile: β = -0.22, 95% CI: -0.36, -0.08). Positive associations between TSH and AGI at birth and at 12 months of age were observed in boys.ConclusionsThis study provides further evidence on the effects of neonatal thyroid function on reproductive development at an early life stage.