Female reproductive studies

Female Reproductive Studies. Before entering a female into a clinical study, it is necessary to have completed the entire reproductive toxicology program, which consists of the following studies. 

Rabbit New Zealand White, SPF, Oryctolagus cuniculus female Reproductive studies including range finding studies in pregnant rabbits, embryo-fetal development study, teratogenecity studies... 

Breast Cancer. Many studies have observed low incidences of hormone-dependent cancers, particularly breast cancer, in Asian countries compared with Western countries and it is becoming increasingly accepted that dietary factors play an important role. Although breast cancer can occur in either males or females, only about 1 % of all cases occur in men, and male breast cancer is a rare disease in all parts of the world." Although there appear to be some similar risk factors for breast cancer in males and females, there is no indication in the literature that diet is either a risk or a protective factor for male breast cancer. The development of breast cancer is known to be highly dependent on the hormones associated with female reproductive functions, while established genetic factors have been... 

In a three-generation reproduction study with DOSS on rats [76] it was shown that administering DOSS in the diet of three successive generations of rats at levels of 0.5% and 1.0% caused a reduction in body weight for parental males in all generations and for FI and F2 females. However, the reduced body weight did not interfere with development of normal reproductive performance. 

In summary, although the available reproductive studies indicate endosulfan has no adverse effects on reproductive performance in animals, adverse effects on male reproductive organs have been seen in young rats and mice. The lack of effects seen in the studies that examined reproductive performance (specifically fertility rate) in treated males and females seems difficult to explain, given the finding of altered spermatogenesis in the more recent studies. 

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... 

Similar results were also observed in a two-generation reproductive study using brown Ranch Wild mink that ingested 0, 16, 45, or 262 mg/kg/day (males) or 0, 20, 57, or 330 mg/kg/day (females) (Bucci et al. 1997). No changes in brain acetylcholinesterase were observed in either the Fj or F2 offspring. 

Liu J, Yu K, Tong S, el al. 1988. [Study on mutagenesis of lead and its influence on female reproductive function] Bulletin of Hunan Medical College 13 132-135. (Japanese)... 

Uterine leiomyomas are the most frequent benign disease of the female reproductive apparatus. At least 20-25% of women of fertile age and 50% of women studied in postmortem have uterine leiomyomas (Stewart 2001 Palomba et al. 2005a). In between 20 and 50% of cases, the uterine leiomyomas cause a clinically relevant symptomatology (such as menorrhagia, infertility, recurrent abortion, pelvic pain, and so on) and treatment is required (Stewart 2001 Palomba et al. 2006a). Thus, this disease is one of the main causes of health expense in the field of gynecology (Stewart 2001 Palomba et al. 2006a). In fact,... 

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]. 

Advantages and Disadvantages. Advantages of using monkeys in safety assessment studies include their phylogenetic proximity, as well as their physiological, behavioral, and, often, metabolic similarities, to humans (Table 16.13). An example is the similarity between the ovarian cycle of female monkeys and women (Mazue and Richez, 1982), which makes the monkey the ideal animal model for reproductive studies. Another advantage associated with most species of monkeys used in safety assessment studies is that they are much smaller than nonrodents such as the dog and, thus like the ferret, require less test compound. 

In a dominant lethal test, treatment of male mice with a single oral dose of 5 mg/kg disulfoton had no effect on male fertility (Herbold 1980). In a three-generation reproductive study, exposure of male and female rats to disulfoton in the diet at 0.5 mg/kg/day resulted a "slight" reduction of litter sizes in... 

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