Reproductive Tissues

Noncontraceptive Uses of Progestins. Progestins have other therapeutic uses aside from contraception. Hormone-dependent tumors and cysts involving reproductive tissues respond to progestins. Megestrol acetate and MPA are the two most commonly used progestins to treat breast cancer... 

OTR is also expressed in male reproductive tissues, like testis, epididymis and in the prostate. OT increases the resting tone of prostatic tissue from guinea pig, rat, dog and human. The activation of these receptors could lead to the contraction of the prostate and the resulting expulsion of prostatic secretions during ejaculation. 

Endosulfan administered by gavage at 1.5 mg/kg/day for 30 days to ovariectomized rats did not influence the relative weights or histology of the uterus, cervix, or vagina compared to ovariectomized control rats that did not receive endosulfan (Raizada et al. 1991). Rats in a positive control group received intraperitoneal injections of estradiol and showed increased relative organ weights and normal development of female reproductive tissues compared to the untreated ovariectomized control rats. 

In vivo studies in animals suggest that endosulfan may disrupt normal reproductive hormone levels in male animals, but that it is not an endocrine disrupter in females. Persistent depressed testicular testosterone was seen in male rats after intermediate duration oral exposures to endosulfan. In ovariectomized female rats, orally administered endosulfan did not induce normal development of female reproductive tissues, and in female mice and immature female rats, acute parenteral exposure to endosulfan did not affect several endocrine-related end points. In vitro studies have evaluated endosulfan for estrogen receptor (ER) and cytosolic protein binding affinity, ER-mediated reporter gene expression, estrogenic induction of cell proliferation, and alteration of relative abundance of active estradiol metabolites. Overall, in vitro evidence in favor of endosulfan estrogenicity indicates relatively weak potency compared to 17[3-estradiol. Apparently contradictory results were reported in different... 

Tinidazole, a second-generation nitroimidazole with protozoal and anaerobic activity, has been available outside the United States for over 30 years.18 Recently, the Food and Drug Administration (FDA) approved it for use in the United States. As a single 2-g dose, tinidazole has an efficacy equivalent to a 2-g dose of metronidazole. Tindazole also has a longer half-life than metronidazole, 14 and 7 hours respectively, and penetrates into male reproductive tissue better than metronidazole. 

Likewise, no treatment-related gross reproductive tract alterations after intermediate-duration exposure were observed in male or female rabbits or in male hamsters continuously exposed to aerosols of Fyrquel 220 at concentrations <100 mg/m3 (MacEwen and Vemot 1983). Two male rabbits exposed for 1-4 hours/day, 4-5 days/week, for 11-26 days to 2,000 mg/m3 aerosol of Cellulube 220 (Carpenter et al. 1959) showed no histological evidence for effects on reproductive tissues. No acute or chronic inhalation studies examining reproductive effects in animals were located. 

In a 2-year feeding study in rats, ovarian interstitial cell hyperplasia was observed in rats exposed to 15 mg/kg/day tricresyl phosphate, but no effect was seen at 7 mg/kg/day (NTP 1994). No effects on male reproductive tissues were seen at < 13 mg/kg/day. No effects on reproductive tissues in either sex were observed in 2-year feeding studies in mice (27 mg/kg/day in males, 37 mg/kg/day in females). 

Finasteride has been clinically proved to reduce the median volume of the prostate in patients and is currently prescribed for the treatment of BPH. The compound also has demonstrated efficacy in the treatment of male pattern baldness and is prescribed for this indication as well. Subsequent to the discovery of finasteride, it was found that there are two isoforms of steroid 5a-reductase in mammals, type 1 and type 2. The type 2 isoform is primarily active in reproductive tissue, while the type 1 isoform contributes to DHT formation in the skin, liver, and reproductive tissue. Finasteride inhibits both isozymes in rats, but selectively inhibits the type 2 isozyme only in humans. It is hypothesized that dual inhibition of both isoforms of steroid 5a-reductase might prove more effective in treating BPH. Hence the GlaxoSmithKline group identified and developed dutasteride (Figure 8.18C). Dutasteride inactivates both human isoforms of steroid 5a-reductase by a mechanism similar to that described for finasteride (Bramson et al., 1997 see also the Web site www.avodart.com). Both finasteride and dutasteride have demonstrated clinical efficacy and are currently used in the treatment of BPH. 

Agusti, J., M. Zapater et al. (2007). Differential expression of putative 9-cw-epoxycarotenoid dioxygenases and abscisic acid accumulation in water stressed vegetative and reproductive tissues of citrus. Plant Sci. 172(1) 85-94. 

PGF2a-1,15-lactone-11-acetate (140) and PGF3ct-l,15-lactone-11-acetate (141) [174-176]. Further, T. fimbria reproductive tissues and egg masses contained a relatively high concentration of saturated and unsaturated long-chain fatty acid esters of PGF2 and PGF3(r (142, 143) [177, 178]. 

Foetal development promotes growth and differentiation of foetal cells and organogenesis Promotes longitudinal body growth and increased body weight Promotes enhanced functioning of the male and female reproductive tissue Promotes growth and differentiation of neuronal tissue... 

Gundersen, D.T. and W.D. Pearson. 1992. Partitioning of PCBs in the muscle and reproductive tissues of paddlefish, Polyodon spathula, at the falls of the Ohio River. Bull. Environ. Contam. Toxicol. 49 455-462. 

Revelli A, Massobrio M, Tesarik J (1998) Nongenomic actions of steroid hormones in reproductive tissues. Endocr Rev 19 3... 

Hendrix SL, McNeeley SG (2001) Effect of selective estrogen receptor modulators on reproductive tissues other than endometrium. Ann NY Acad Sci 949 243-250... 

Qu Q, Zheng H, Dahllund J, Laine A, Cockcroft N, Peng Z, et al. (2000) Selective estrogen effects of a novel triphenylethylene compound, FC1271a, on bone, cholesterol level, and reproductive tissues in intact ovariectomized rats. Endocrinology 141 809-820... 

Nuttall ME, Nadeau D, Stroup G, Hoffman S, Vasko-Moser J, Gowen M (1998) Idoxifene antagonizes the effects of estrogen in the breast and endometrium a therapeutically favorable profile over estrogen in reproductive tissues. In ASBMR IBMS joint meeting, San Francisco, December 1998. Bone 23(Suppl) S611... 

Prenatal and postnatal exposures to fenvalerate reduced prostate and seminal vesicle weights and plasma testosterone levels in male rats [55], A chronic study showed no adverse effects on reproductive tissues at a high dose level of 1,000 ppm [142]. In vivo and in vitro studies with rats and mice suggested that fenvalerate may affect male and female reproduction, possibly due to calcium transport alteration [143-146], One paper reported that fenvalerate affected human sperm count and sperm motility of male workers who were exposed to fenvalerate in a pesticide factory [147]. 

In contrast, no reproductive effects were observed in male Sprague-Dawley rats exposed to 500 ppm -hexane 22 hours a day for 6 months (IRDC 1981). No treatment-related lesions were noted in any of the reproductive tissues examined (seminal vesicles, prostate, testis, epididymis). Similar results were reported in both sexes of weanling Fischer 344 rats exposed to up to 10,000 ppm -hexane 6 hours a day, 5 days a week for 13 weeks (Cavender et al. 1984). No treatment-related histopathologic lesions were present in any of the following reproductive tissues ovaries, uterus, oviducts, vagina, cervix, seminal vesicles, prostate, testis, or epididymis. 

Target Organ Toxicity. -Hexane exposure is documented to cause toxicity in peripheral nerves of humans (both sensory and motor). In rats, -hexane exposure causes toxicity in the peripheral and central nervous system and in male reproductive tissues. Effects on respiratory tissue have been observed in mice and rabbits. The toxic agent in nervous system and reproductive tissues is believed to be the -hexane metabolite 2,5-hexanedione (Graham et al. 1995). 

Reproductive Effects. Reproductive effects have not been examined in humans after exposure to -hexane. A dominant-lethal test in mice showed no effect on male fertility (Litton Bionetics 1980). No effects were seen on reproductive tissues in male rats after intermediate-duration inhalation exposure at 500 ppm (IRDC 1981) or in either sex of mice after intermediate-duration inhalation exposure to up to 10,000 ppm -hexane (Dunnick et al. 1989 NTP 1991). However, inhalation exposure in male rats to higher concentrations of -hexane showed effects after acute-duration exposure to 5,000 ppm (spermatid and spermatocyte degeneration and exfoliation) and atrophy of testicular germinal epithelium after intermediate-duration exposure to 1,000 ppm (De Martino et al. 1987 Nylen et al. 1989). Testicular atrophy in rats was also noted after intermediate-duration oral exposure at 4,000 mg/kg/day (Krasavage et al. 1980). Similar to -hexane neurotoxicity after inhalation exposure, effects on the testes in rats can be reproduced by oral administration of the w-hexane metabolite 2,5-hexanedione (Chapin et al. 1982 ... 

Simon GS, Egle JL, Dougherty RW, et al. 1986. Dominant lethal assay of chlordecone and its distribution in the male reproductive tissues of the rat. Toxicol Lett 30 237-245. 

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