Male Reproductive Tract Organs Research Articles

OR25-1 Bilateral and Unilateral Malformations of Male Reproductive Tracts in Mice with Androgen Receptor Gene Deletion in the Mesenchyme

Abstract Congenital unilateral defects of male reproductive tracts have been documented in men, suggesting the potential left-right asymmetry in male reproductive tract development. However, classic textbooks of endocrinology have been teaching us that the development of the paired male reproductive tract is governed by the universal action of the androgen receptor (Ar). During sexual differentiation, testis-derived androgens activate the Ar to promote the stabilization of the bilateral Wolffian ducts, the progenitor for the male reproductive tract. The Wolffian ducts then differentiate into the paired male reproductive tract organs, which include the epididymes, vas deferentes, and seminal vesicles. The Ar is expressed both in the epithelium and mesenchyme of the male reproductive tract during fetal development. Landmark tissue recombinant studies and the observation of normal morphology in the epithelium-specific Ar knockout mouse all support the notion that Ar action in the mesenchyme dictates the morphogenesis of the male reproductive tract. However, no genetic study has been performed to investigate the consequence of the loss of mesenchymal Ar on male reproductive tract development. To test the functional significance of the mesenchymal Ar, we designed a mesenchyme-specific Ar knockout mouse model (ARcKO) to ablate Ar specifically in the mesenchyme prior to the initiation of sexual differentiation. We performed immunohistochemistry of AR to confirm that Ar expression was absent in the mesenchyme while epithelial Ar remained intact in this ARcKO model. Based on the widely accepted notion that mesenchymal Ar regulates epithelial morphogenesis of the male reproductive tract, we expected to see abnormal patterning of the male reproductive tract. Indeed, the epididymis lost its characteristic coiling and became cystic. However, 40% of the 23 collected ARcKO males displayed these abnormalities on both horns; 43% and 17% displayed these abnormal phenotype solely on the left and right horn, respectively. This surprising observation might result from asynchronous activities of Cre on the left and right horns. However, when the Cre was crossed with a reporter (tdTomato), we observed comparable reporter expression on both horns at the onset of sexual differentiation of reproductive tracts. These observations suggest that the developmental programs in the morphogenesis of the left and right male reproductive tracts are asymmetrical and there could be a compensation mechanism for the loss of mesenchymal AR. We are currently in the process of comparing the left and the right horns in Ar knockout male mice to determine any biased signaling. Taken together, our study provides a unique model for not only studying congenital defects of male reproductive tracts but also for investigating the potential asymmetry in the masculinization program. Presentation: Monday, June 13, 2022 11:00 a.m. - 11:15 a.m.

Reduction of Female Mating Receptivity after Injection of Male-Derived Extracts inTrigonotylus caelestialium(Heteroptera: Miridae)

AbstractThe effects of male-derived extracts on female receptivity to remating were investigated in Trigonotylus caelestialium (Kirkaldy) (Heteroptera: Miridae). The aqueous extracts of male reproductive tracts were observed to reduce receptivity both at 3 h and at 1 d after injection into the abdomens of females. Next, ultrafiltration was used to divide the aqueous extracts of the male reproductive tracts into three molecular-weight (MW) fractions: <3.5 kDa, 3.5–14 kDa, and >14 kDa. The filtrate containing the MW substances <3.5 kDa reduced female receptivity 3 h after injection, whereas the fraction containing MW substances >14 kDa inhibited receptivity at 1 and 2 d after injection. Finally, the male reproductive tract organs were divided into the accessory glands, testes, and the remaining reproductive organs, including the seminal vesicles. Aqueous extracts of the accessory glands reduced the receptivity of females both at 3 h and 2 d after injection, whereas those of the testes decreased the receptivity of females at 3 h after injection. Together, the results indicate that more than one mechanism may be involved in the effects of male-derived substances on female receptivity in T. caelestialium. The findings suggest that low-MW male-derived substances in the accessory glands and testes cause short-term inhibition and that the high-MW substances in the accessory gland inhibit female mating at a later period.

Mechanism underlying transient gestational-onset hypothyroidism–induced impairment of posttesticular sperm maturation in adult rats

To understand the mechanism underlying gestational-onset hypothyroidism-induced male infertility. Controlled laboratory study. Research laboratory in a university department of endocrinology. Wistar rat. Pregnant rats were exposed to methimazole from embryonic days 9 to 14, 18, and 21, covering specific fetal periods of differentiation and development of male reproductive tract organs. Fertility of male rats was assessed by testing sperm count, forward motility, and in vivo fertilizing ability. Secretory activity of the epididymis was evaluated by quantifying sialic acid, carnitine, and glycerylphosphorylcholine. Bioavailability of androgens was assessed by quantifying testosterone in serum and testicular interstitial fluid and epididymal 5alpha-reductase activity/mRNA expression. Androgen receptor (AR) status in the epididymis was tested by detecting the expression levels of its mRNA and protein, as well as ligand binding activity. Data were analyzed statistically by one-way analysis of variance. Gestational exposure to methimazole decreased sperm forward motility, in vivo fertilizing ability, bioavailability of androgens, AR status, and secretory activity of the epididymis in adult rats. Transient gestational-onset hypothyroidism affects male fertility by impairing posttesticular sperm maturation process in the epididymis, owing to subnormal androgen(s) bioavailability, AR expression, and AR functional activity.

Female mating receptivity after injection of male-derived extracts in Callosobruchus maculatus

The effects of male-derived extracts on female receptivity were investigated in Callosobruchus maculatus (Coleoptera: Bruchidae). Injection of aqueous extracts of the male reproductive tract into the abdomen of females reduced receptivity. Aqueous extracts of male reproductive tracts were divided to three molecular weight (MW) fractions by ultrafiltration: Fractions: (I) MW < 3 kDa, (II) 3–14 kDa, and (III) >14 kDa. Fraction II reduced female receptivity from 3 h after injection, and Fraction III reduced female receptivity from 2 days after injection. On the other hand, no effect on receptivity was found for Fraction I. Furthermore, male reproductive tract organs were divided into accessory gland, testis, and seminal vesicle including the ejaculatory duct. Aqueous extracts of the seminal vesicle reduced receptivity of females immediately following injection, while aqueous extracts of the accessory gland reduced receptivity at the second day. The results suggest that the components of Fraction II existed in the seminal vesicle, and those of Fraction III in the accessory gland. The results of the present and the previous studies in Callosobruchus chinensis, a species closely related to C. maculatus, were compared and are discussed from the viewpoint of the significance of ejaculation in the two species.

Female mating receptivity inhibited by injection of male-derived extracts in Callosobruchus chinensis

The effects of male-derived extracts on female receptivity to remating were investigated in Callosobruchus chinensis (Coleoptera: Bruchidae). Injection of aqueous extracts of male reproductive tracts into the abdomen of females reduced receptivity. When aqueous extracts of male reproductive tracts were divided to three molecular weight (MW) fractions by ultrafiltration: <3, 3–14, and >14kDa, the filtrate containing MW substances <3kDa reduced female receptivity 3h and 1 day after injection, whereas the fraction containing MW substances >14kDa inhibited receptivity 2 and 4 days after injection. Finally, male reproductive tract organs were divided into accessory gland, seminal vesicle, and testis. Aqueous extracts of testis reduced receptivity of females on the second day and at 3h, and aqueous extracts of accessory gland reduced receptivity of females on the second day after injection. On the other hand, aqueous extracts of seminal vesicle did not reduce female receptivity. The results indicate that more than one mechanism may be involved in producing the effects of male-derived substances on female receptivity; low MW male-derived substances, which possibly exist in testis, cause short-term inhibition, while high MW substances, which possibly exist in the accessory gland, inhibit female mating later than low MW substances in C. chinensis.

Neonatal low- and high-dose exposure to estradiol benzoate in the male rat: II. Effects on male puberty and the reproductive tract.

Environmental contaminants with estrogenic properties have been cause for heightened concern about their possible role in inducing adverse health effects. Brief exposure of rodents to high doses of natural estrogens early in life results in permanent alterations of the male reproductive tissues, but the question of whether environmentally relevant doses can cause the same effects remains controversial. The current project was designed to determine the dose-response relationship between neonatal estradiol exposure and the development of the male reproductive tract in the rat. Neonatal male Sprague-Dawley (SD) and Fisher 344 (F344) rats were exposed to beta-estradiol-3-benzoate (EB) at concentrations ranging from 0.015 microg/kg body weight (BW) to 15.0 mg/kg BW and 0.15 microg/kg BW to 1.5 mg/kg BW, respectively. Results showed an inverted U-shaped dose-response profile for testis and epididymis weights in 35-day-old SD rats, with increased organ sizes at the low-dose end of the treatment. This effect was transient and was not sustained into adulthood. Increased hepatic testosterone hydroxylase activities in low-dose animals suggest an advancement of puberty as the cause for increased reproductive organ weights. On postnatal day (PND) 90, a stimulatory low-dose response to EB was present in SD rat testicular and epididymal weights, however at one order of magnitude lower dose than that seen on PND 35, suggesting a separate effect. All SD male reproductive tract organs and serum hormones showed a permanent inhibitory response to high doses of neonatal EB. F344 rats exhibited greater estrogen sensitivity on PND 90. Despite this heightened responsiveness, F344 rats did not exhibit a low-dose effect for any endpoint. These low-dose responses to estradiol are organ and strain specific.

Multiple drug resistance mutations in human immunodeficiency virus in semen but not blood of a man on antiretroviral therapy

The concept that the male reproductive tract harbors isolated reservoirs of human immunodeficiency virus (HIV) infection has now been widely accepted. The significance of semen viral burden to sexual transmission of HIV is obvious; however, its contribution to disease progression is unknown. We report a case study that demonstrates the emergence of resistance-conferring mutations to antiviral therapy in infected seminal leukocytes from a man with asymptomatic prostatitis associated with leukospermia. This finding demonstrates the potential importance of male reproductive tract organs to the development of therapy resistance in HIV-infected men.

Human immunodeficiency virus in semen

Infected semen is a principal mode of spread of the HIV disease. The characteristics of male reproductive tract organs that protect spermatozoa from immunologic attack may also create a unique environment for HIV. Understanding the pathobiology of HIV in the male reproductive tract is therefore essential for the design of effective strategies of prophylaxis and treatment.

Evaluation of the site of synthesis of rabbit sperm acrosome stabilizing factor using immunocytochemical and metabolic labeling techniques.

Antibodies to rabbit acrosome stabilizing factor (ASF) were raised in mice and proved monospecific on Western electroblots . Anti-ASF was utilized to immunolabel tissue sections of male reproductive tract organs. Staining of principal cell cytoplasm was observed primarily in the corpus epididymidis (Regions 6 and 7), and secondarily in the cytoplasm of principal cells of the distal cauda epididymidis (Region 8b ) and the columnar cells of the vas deferens epithelium. The microvilli of principal cells in the proximal cauda epididymidis (Region 8a ) were densely stained. Spermatozoa appeared uniformly stained within the lumen of the corpus epididymidis and staining intensity increased distally. The Golgi region of corpus principal cells was not stained, nor were other cell types in this region. Testis, caput epididymidis, and accessory sex organs were not stained. Synthesis of ASF by corpus epididymidis was shown by immunoprecipitation of radiolabeled ASF from organ cultures of specific epididymal segments. Scant amounts of synthesis were also detected in the cauda epididymidis and vas deferens. The large subunit of ASF, immunoprecipitated from the corpus epididymidis, is 2000-4000 daltons larger than the large subunit of ASF from more distal regions of the reproductive tract, suggesting modification of this component.