Document 2qYrX6rNV7RELqxkoXVREaMda

pCR . effect-i on mammalian reproduction . . . By .. J, E. KihlotrOm, J, Orberg, C. Lundberg, P. O, Danieleson and J. Sydhoff Institute of Zoophyelology, Uppsala Sweden Like many other chlorinated hydrocarbons PCB enhances the hepatic metabolism of sex steroids such as testosterone and estradiol (Peakall 1967, Nowicki and Norman 1972). It might therefore be suspected that toe occurrence of PCB in animals would disturb the sexual functions and, perhaps,cause a decrease of the procreative ability of the animals, resulting in a continued decrease of the number of Individuals per generation. From this point of view we have studied some sexual Junctions In mice of the NMRI-straln, given PCB In amounts corresponding to those found in wild life (Jensen et al, 1969, Jensen and Odsjd 1972). 1. Length of the estrous cycle,. The occurrence of heat In female animals Is dependent upon the amount of estrogeno circulating in the body. Consequently, a change In the catabolism of these hormones could be suspected to change the regular reappearing of heat periods. Therefore, we have studied the estrous cycle In mice by means of daily vaginal smears before and after one single lntraperlotoneal injection of PCB (Cloplien A 60, 20 mg/kg body weight). As seen fromtfbe following tablet the mean length of the estrous cycle Increases upon administration of PCB (Orberg et al, 1972). .Length of_the_e stjrou(j. cycle befor_ and after onj jingle^Injection qiPCg ^20 body weight) Number of animals Control animals Experimental animals 24 IZ Total number of cycles studied 96 48 Mean length In days Before After Injection Analyst# P 5.6 5,6 1.81 0.04 5.5 6.6 ii il ., 4 . DSW 032251 STLCOPCB4016213 -z- Howevcr, in the natural state PCB mainly enter* tho animal* in food and water. For this reason we have given mice PCB orally, die solving the drug in peanut oil. Mice happen to have a fancy for peanut oil and,consequently they consume the oil portions immediately and completely. The dose was 0, 025 mg PCB/day/ /animal, approximately corresponding to 5 ppm in the food, and the experiments lasted for 62 daya. The controls were given the corresponding volume of the peanut oil vehicle. The results are given in the following table (Orberg and KihlstrOm 1972), .. Effectsjpf_ingeeto_d_PCBJO,02Jj n\g,/dajr/anlrnial_for_62 Juce8*lve_da-jrj)_uopithe longth_ojf the jsstrous. cycl Number of animals Control animals 14 Experiment tel animals n Total number of cycles studied 120 69 Mean length, days 6.6 8.7 Analysis t P< 5. 79 0. 0005 Tho observed prolongation of the estrous cycle Implies a prolonged interval between the short periods of sexual receptivity In females, probably resulting in a decreased number of pregnancies per individual, 2. Frequency of implanted ova 2,1, Fonoahsj ingeeting_PCB a_a_dult* The process of Implantation of fertilised ova In the uterus demands a very subtle balance between progesterone and estradiol. This balance might be disturbed by an Increased metabolism of these steroids. For this reason we counted the num ber of corpora lutea and Implanted embryo* In females Ingesting 0.025 mg PCB/day/anlmal during 62 day* before being mated and also during early preg nancy until being sacrificed on day 8-10 of pregnancy. The results given below (CJrbcrg t al, 1972) show a decreased frequency of implanted ova In the treated animals. OSW 032252 STLCOPCB4016214 y rcgucnc^ oMmgl anted ova _in_fmaje _inggstingJPCB JO^ 02b mgy/dajr^animalJ Control animals Experi mental animals Number of animals 22 23 Number of cor pora lutea 288 313 Number of ova Per cent of , Implanted ova implanted "XT P < 250 87 5.60 0. 025 249 80 2,2 Malea and females sucking PCB-containlng milk , It is well known (Harris 1965 and others) that the tax steroids present during the early postnatal period determine the development o the sexual (unctions and thus influences the reproductive ability o( the adult animal. Sucking o( PCBcontaining milk during this period, possibly resulting in an increased catabo lism of steroids, could therefore be deleterious to the sexual activity in the adultb. In order to tackle thle question we reared 20 different Utters of mice. On the day of parturition ten mothers were given 50 mg PCB/kg body weight intrapcritoneally and the ten remaining mothers the corresponding volume of the oil ' vehicle. Tho injections were repeated once a week throughout the period of lactation. When reaching sexual maturity the young animals coming from these litters were mated according to the scheme In the table below. The pregnant females were sacrificed on day 10-12 of pregnancy and the number of corpora lutea and placentae counted. The experiments are still going on. Consequently, the results in the following table are preliminary. When mating a control animal with an experimental one no effects upon the frequency of implantation have been observed so far. However, when both the animals of *e(tuple had been sucking PCB-containing milk there is a significant decrease in the frequency of implanted ova. Freguencj of__implanted ova_in_animals Jhaylng .sucked PCB-contahiing_ mUk_ Paired animals Male Female Control Control Experi- Control mental Control Experi mental Experl- Experimental mental Number of pairs 16 17 19 21 Number of otrpora lutea 211 216 240 262 Implanted ova Number Per cent Analyst a P- 199 94 - * 200 93 0. 27 0.7 219 91 1.13 0. 3 191 73 35. 57 0.0005 Thus, even small doses of PCB, given for short periods, may cause a decrease inthc number of youngs per litter in mice. DSW 032253 STLCOPCB4016215 References Harris, G.W, Endocrinol. 75, 627, 1967, Jensen, S. and OdsjO, T,, Personal communication 1972, Jensen, S. , Johnels, A, G., Olason, M. and Otterllnd, G, Nature 224. 247, 1969, Nowicki, H, G. and Norman, A, W, , Steroids 19, 85, 1972, Peakall, D. B,, Nature 216, 505, 1967, . Orbcrg, J, and Klhlstrdm, J. E, In manuscript. 1972. Orberg, J., Johansson, N,, KihlstrOm, J, E, and Lundberg, C, Amblo 1. 148, 1972. DSW 032254 STLCOPCB4016216