The effects of vagotomy on compensatory ovarian hypertrophy and follicular activation after unilateral ovariectomy.код для вставкиСкачать
THE ANATOMICAL RECORD 214%-66 (1986) The Effects of Vagotomy on Compensatory Ovarian Hypertrophy and Follicular Activation After Unilateral Ovariectomy HUBERT W. BURDEN, IRVIN E. LAWRENCE, JR.,CARLTON P. SMITH, JR., JEANNE HOFFMAN, MARILYN LEONARD, DONALD J. FLETCHER, AND CHARLES A. HODSON Departments of Anatomv IH. W B.. I. E. L.C.PS.. J. H.. M. L.D.J . E ) and Obstetrics a n t i Gvneco1og.v fC.A.H.). School o f Metircrnc~.Enst Corolinn Uniuersit.v. Grc.c,rrr-rlle, NC27834 ABSTRACT Following unilateral ovariectomy in the rat, the remaining ovary undergoes rapid compensatory changes including a n increase in the number of antral follicles (follicular activation) and a n increase in ovarian weight (compensatory ovarian hypertrophy). The ovary is innervated by the vagus nerve (Burden et al., 1983). In the present study, the effects of right and left cervical vagotomy and abdominal vagotomy on follicular activation and compensatory ovarian hypertrophy in the remaining right or left ovary were compared 15 days after unilateral ovariectomy. Neither right nor left cervical vagotomy affected compensatory ovarian hypertrophy of the right or left ovaries but abdominal vagotomy depressed compensatory ovarian hypertrophy in both the right and left ovaries. Left cervical vagotomy did not inhibit follicular activation, but right cervical vagotomy prevented follicular activation in the right but not left ovary. Also, abdominal vagotomy inhibited follicular activation in the right but not the left ovary. In animals with both ovaries which were subjected to the left or right cervical vagotomy or abdominal vagotomy follicular counts in both right and left ovaries were similar. Collectively, these data indicate that the vagus nerve participates in follicular activation after unilateral ovariectomy. The data also indicate that the right ovary is more dependent on vagal influences for follicular activation than the left ovary. Removal of one ovary from a cycling rat results in a n increase in the number of antral follicles [follicular activation (FA)] and a n increase in ovarian weight [compensatory ovarian hypertrophy (COH)] (Hatai, 1913; Arai, 1920). Twice the normal number of ova are produced by the remaining ovary in the next cycle (Peppler and Greenwald, 1970). This follicular compensation is attributable to a n increased proliferation of smaller follicles rather than decreased follicular atresia and results in a doubling of the number of large follicles which ultimately mature (Peppler and Greenwald, 1970). The proliferation of small antral follicles and increased ovarian weight subsequent to unilateral ovariectomy (ULO) are believed to result from increased pituitary gonadotropin secretion brought about by decreased serum concentrations of ovarian steroids, i.e., reduced negative feedback (Ramirez and Sawyer, 1974; DeGreef et al., 1975). However, Aron et al. (1948) noted the rapidity of compensatory ovarian responses subsequent to ULO and suggested that nerves were also involved in this phenomenon. Recently, our laboratory (Burden and Lawrence, 1977; Curry et al., 1984) and others (Gerendai and HaIasz, 1976; Gerendai et al., 1978; Gerendai, 1979; 1980; Nance et al., 1983) have reported results which corroborate the suggestion that nerves are involved in compensatory ovarian responses. 0 1986 ALAN R. LISS. INC. The existence of direct neural connections between the hypothalamus and ovaries has been postulated (Gerendai, 1979; Gerendai, 1980; 1984; Gerendai and Halasz, 1981; Kawakami et al., 1981; Nance et al., 1984) and recently the existence of a functional difference in the two halves of the hypothalamus in neuroendocrine regulation has been proposed (Nance et al., 1980; 1983; 1984; Mizunuma et al., 1983; Gerendai, 1984). There is evidence that sensory components from the vagus nerve terminate in the ovary (Burden et al., 1983); however, the precise intraovarian site of these terminals has not been determined. We have previously shown that abdominal vagotomy decreased COH after ULO (Burden and Lawrence, 1977). In the present study, we analyzed the effects of right vs. left cervical vagotomy and abdominal vagotomy on compensatory weight gain of the ipsilateral and contralateral ovary. We also morphometrically analyzed the effects of these neural lesions on the proliferation of follicles in the ovary remaining after unilateral ovariectomy. Because of the possible nonspecific debilitating effects of abdominal vagotomy, we also determined the effects of this surgery on selected functional aspects of an additional endocrine Received May 24,1985; accepted August 25,1985. H.W. BURDEN ET AL. 62 TABLE 1. Effect of right (R) or left (L) cervical vagotomy (CV) or abdominal vagotomy (AV) on body weight (mean f SEM) and ovarian weight (mean f. SEMI on day 15 after surgery Body weight (g) Group day 1 Body weight (g) day 15 Left ovary weight (mg) Right ovary weight (mg) Sham (ovaries and vagi exposed) (6)' 191.0 f 2.7 219.6 f 4.2 30.5 f 1.9 30.9 k 3.0 LCV (10) RCV (9) AV (6) 189.2 f 1.9 189.4 2.9 196.0 k 4.9 220.3 f 4.3 213.6 f 4.8 188.5 f 14.2* 34.1 f 1.8 31.4 +_ 2.6 20.7 f 2.2** 36.5 f 2.0 28.6 k 2.0 23.6 k 2.2*** + 'Number of rats in parentheses. *Significantly different from Sham and LCV (P < ,051. **Significantly different from other groups (P < .05). ***Significantly different from LCV (P < .05). gland, viz., the endocrine pancreas. This organ is in- glucagon, and somatostatin were assayed. Serum from volved in numerous metabolic processes and is known trunk blood collected at the time of death was also frozen to be innervated by the vagus (see review by Miller, and later assayed for glucose and insulin concentration. 1981) and we felt it might be a site where generalized Glucose and Hormone Determinations debilitating effects would be manifested. Serum glucose was measured by the micromethod of MATERIALS AND METHODS Hoffman (1937) using a Technicon autoanalyzer (TechAnimals nicon Instruments, San Francisco, CAI. Insulin was deNulliparous Sprague-Dawley rats obtained from the termined by radioimmunoassay (Morgan and Lazarow, Animal Resources Center, East Carolina University, 1963) with crystalline rat insulin (Novo Research Instiwere used in the study. All animals were 8-9 weeks old tute, Copenhagen, Denmark) for the standard. Guinea and weighed between 180 and 200 g at the initiation of pig anti-insulin serum and rabbit anti-guinea pig serum the study. The rats were housed in a room with con- were raised and characterized in our laboratory. Gluca trolled lighting (lights on 0500-1900 hours) and pro- gon was measured by radioimmunoassay (McEvoy et al., vided food and water ad libitum. The estrous cycle was 1977)with antiserum 2OC (provided by Dr. R.C. McEvoy, monitored daily by vaginal lavages and only those rats Mount Sinai School of Medicine) and porcine pancreatic showing two consecutive 4-5-day cycles were used in glucagon (Novo Research Institute) for standard. Somatostatin was determined by radioimmunoassay experiments. (Fletcher et al., 1980)with synthetic cyclic somatostatin General Surgical Technique (Calbiochem Biochemicals, San Diego, CA) and antiAnimals were anesthetized at estrus (day 1) with serum R10 (provided by Dr. J.K. Stewart, Virginia Comchloral hydrate (350 mgikg intraperitoneally) and either monwealth University). The intra- and interassay left or right cervical vagotomy or abdominal vagotomy coefficients of variation for the insulin assay were 2.8% was performed. For cervical vagotomy, the vagus nerve and 11.1%, respectively; for glucagon, 2.8% and 9.3%; was isolated from the carotid sheath and a 5-mm portion for somatostatin, 2.5% and 6.9%. of the nerve was resected. For abdominal vagotomy, the Morphometric Analysis liver was reflected, the esophagus was exposed, and the anterior and posterior vagal trunks were separated from Ovaries were embedded in paraffin, serially sectioned the esophagus and carefully avulsed with fine forceps. a t 7 pm, and stained with hematoxylin and eosin. The The presence of a n enlarged distended stomach was tissue was viewed with a Zeiss Photomicroscope I1 interinterpreted as positive evidence for a complete abdomi- faced with a n Apple ne Microcomputer and a Bioquant nal vagotomy. In sham-operated animals, the cervical II (R&M Biometrics, Nashville, TN) image analysis sysvagus was exposed bilaterally, but not cut. In the unilat- tem. The procedure for counting follicles was modified eral ovariectomy studies, either the left or right ovary from Peppler (1971). Briefly, each section was examined was exposed through a dorsolateral incision, ligated at and antral follicles containing a n oocyte with a nucleothe hilar area, removed, weighed, and fixed in Bouin's lus were measured. Follicles containing a n oocyte with solution. At day 15, all animals were decapitated, and a pyknotic nucleus or ten or more granulosa cells with the remaining ovary was weighed and fixed in Bouin's pyknotic nuclei were designated atretic. All antral follisolution for morphometric analysis. cles, both healthy and atretic, were assigned to one of The pancreas was dissected, trimmed of gut and major three size classifications: 150-415 pm, 416-570 pm, and lymph nodes, weighed, and kept a t 0°C until homogeni- over 570 pm diameter. These diameters were calculated zation. Cold acid-ethanol was added and the pancreas from area measurements based on the assumption that was homogenized using a Polytron homogenizer (Brink- the follicles were spheres. To obtain follicular area (pm'), mann Instruments, Westbury, NY). Homogenates were the microscope image was projected on a television monheated for 5 minutes in a 70°C water bath, adjusted to itor interfaced with a digitizer pad. The projected follicle a volume a t 5 ml, and stored at -20°C until insulin, was measured utilizing the digitizer pad and cursor of 63 VAGOTOMY AND OVARIAN HYPERTROPHY TABLE 2. Effect of right (R)or left (L) cervical vagotomy (CV) or abdominal vagotomy (AV) on body weight (mean SEMI and weight of the remaining ovary (mean f SEMI on day 15 after unilateral ovariectomy (ULO) in rats Group 1 RULO (913 LULO (7) LCV-RULO (14) LCV-LULO (21) RCV-RULO(14) RCV-LULO (18) AV-RULO (16) AV-LULO (15) Body weight (g) day 1 Body weight (g) day 15 Weight (mg) of initial ovary Weight (mg) of remaining ovary 187.8 f 2.8 188.1 f 1.9 190.2 k 2.0 187.5 f 1.3 189.1 & 2.0 191.2 + 2.0 192.8 f 1.8 189.0 f 1.7 220.4 f 3.7 214.0 f 3.0 215.4 f 2.7 215.3 f 2.1 213.5 f 2.5 219.1 k 2.9 190.4 f 9.7 166.2 f 8.7* 36.2 -)r 1.0 38.0 f 2.0 31.7 f 2.0 29.5 1.3 29.5 f 1.4 31.0 f 0.7 35.3 f 1.2 33.0 1.3 55.4 f 2.2 56.0 + 3.0 51.3 k 1.7 48.8 f 1.7 49.5 f 1.1 48.8 + 1.4 34.6 f 2.6 31.1 +_ 3.1 Percent gain in ovarian weight',' * 53.4 5.3 48.2 f 6.1 67.2 f 8.0 69.5 k 7.4 72.2 k 8.1 58.1 f 4.3 -2.4 f 6.6* -2.2 + 9.5" 'Calculated in relation to initial ovary weight. 'ARCSIN conversion was used for calculation of significance of percent gain in body weight. 3Number of rats in parentheses. *Significantly different from other groups (P < ,0001). TABLE 3. Effect of abdominal vagotomy at estrus (day I) in unilaterally ovariectomized rats on serum and pancreas parameters (mean f SEM) 15 days later Group Sham Abdominal (g) Insulin concentration (ng/mgwet weight) Glucagon concentration (ng/mg wet weight) concentration (ngimg wet weight) 0.70 k 0.04 (12) 0.75 k 0.04 (13) 50.6 f 5.3 (12) 44.3 f 3.0 (13) 2.11 f 0.17 (12) 2.46 f 0.16 (13) 0.19 k 0.03 (12) 0.21 k 0.02 (13) Serum glucose (mg/dl) Serum insulin (ng/ml) Wet weight pancreas 129 f 3 (19)l 126 f 5 (13) 1.5 f 0.1 (19) 1.4 k 0.2 (13) Somatostatin vapotomv 'Number in parentheses is number of animals. the image analysis system. The basement membrane of ble 2). Also, abdominal vagotomy combined with either the follicle image was circumscribed and the measure- left or right unilateral ovariectomy reduced ovarian weight at day 15 (Table 2). ment so obtained was stored for subsequent analysis. Statistics Pancreatic Weight and Islet Hormone Values Multisample numerical data were analyzed by analysis of variance (ANOVA). If significance was obtained with ANOVA, the Scheffe's test was used for group comparisons. Differences between right and left ovarian weights and right and left ovarian follicle populations in animals with both ovaries were assessed with the paired t test. Also in the ULO study, the number of follicles in the remaining ovary a t day 15 was compared to the number at day 1using the paired t test. Glucose, insulin, glucagon, somatostatin, and pancreatic weight values in sham-operated and vagotomized rats were compared with the Student's t test. Abdominal vagotomy did not alter serum levels of insulin or glucose, pancreatic wet weight, or the concentration of insulin, glucagon, or somatostatin in the pancreas (Table 3). RESULTS Body and Ovary Weights Ovarian Follicles In rats bearing both ovaries, neither right nor left cervical vagotomy nor abdominal vagotomy at day 1 altered the number of follicles in the right or left ovary at day 15 (Table 4). In the sham-operated rats, there were more healthy large antral follicles in the right ovary (Table 4). After left or right unilateral ovariectomy at day 1, there was a n increase in the number of healthy antral follicles in a t least one size category in the remaining ovary at day 15 (Table 5). This ovarian response is referred to as follicular activation (FA). Left cervical vagotomy did not alter FA in the left or right ovary, but right cervical vagotomy inhibited FA in the right, but not left ovary. Likewise, abdominal vagotomy also inhibited FA in the right, but not the left ovary (Table 5). ' In animals bearing both ovaries, neither sham surgery nor left or right cervical vagotorny altered body weight nor left or right ovarian weight on day 15 after surgery. In contrast, abdominal vagotomy depressed body weight and both left and right ovarian weight at this time (Table 1). In rats subjected to unilateral ovariectomy, neither DISCUSSION sham surgery nor left or right cervical vagotomy altered The results of the present study indicate that compenbody weight or ovarian weight at day 15 (Table 2). In contrast, abdominal vagotomy combined with left uni- satory weight gain of the remaining left or right ovary lateral ovariectomy reduced body weight at day 15 (Ta- after ULO is not altered by ipsilateral or contralateral 64 H.W. BURDEN ET AL TABLE 4. Effect of right (R) or left (L) cervical vagotomy (CV) or abdominal vagotomy (AV) at estrus on follicular development (mean number of follicles f SEM) in the right and left ovary 15 days after surgery Group Sham (4)' Right ovary Left ovary RCV (4) Right ovary Left ovary LCV (4) Right ovary Left ovary AV (4) Right ovary Left ovary 150-415 p m 416-570 p m Over 570 pm Healthy Atretic Total antral follicles Healthy Atretic Healthy Atretic 55.5 f 2.4 52.5 f 12.0 27.0 f 3.5 23.0 f 5.9 16.5 f 1.6 17.3 t 5.7 7.5 f 0.6 10.3 rf- 1.1 2.5 f 0.6 1.5 0.6 1.3 f 0.5 O* 0.8 f 0.5 0.5 f 0.3 40.5 k 5.0 47.5 f 11.3 18.5 f 3.6 21.8 k 8.1 14.3 k 1.9 16.8 f 2.9 2.3 k 1.3 3.8 f 1.3 0.5 f 0.5 1.3 f 0.6 4.0 f 1.4 3.8 f 1.5 0.8 f 0.8 0.3 f 0.3 56.8 f 5.2 52.5 f 4.7 30.5 f 3.6 30.0 f 3.0 20.3 f 3.1 15.0 f 2.3 5.0 f 2.0 4.5 f 1.7 0.8 f 0.5 2.0 f 0.7 0.3 f 0.3 0.5 f 0.3 0 0.5 f 0.3 42.3 f 6.6 43.8 f 6.5 18.0 f 2.3 17.0 t 2.1 19.8 ir 3.3 21.0 f 5.1 4.0 ir 1.5 4.3 f 1.8 0.5 f 0.5 1.5 f 0.6 0 0 0 + 0 'Number in parentheses is number of animals. *Significantly different from right ovary (P < .05). TABLE 5. Effect of right (R) or left (L) cervical vagotomy (CV) or abdominal vagotomy (AV) and R or L unilateral ovariectomy NJLO)at estrus (day 1) on follicular activation (mean number follicles f SEM) in the remaining left or rkht ovary 15 days later Group Right ULO (4)' Day 1R ovary Day 15 L ovary Left ULO (3) Day 1L ovary Day 15 R ovary LCV-RULO (4) Day 1R ovary Day 15 L ovary LCV-LULO (5) Day 1L ovary Day 15 R ovary RCV-RULO (4) Day 1R ovary Day 15 L ovary RCV-LULO (3) Day 1L ovary Day 15 R ovary AV-RULO (3) Day 1R ovary Day 15 L ovary AV-LULO (4) Day 1L ovary Day 15 R ovary 416-570 p m 150-415 pm Total antral follicles Healthv 53.3 If- 9.6 78.8 f 7.2 Over 570 p m Healthv Atretic Atretic Healthv Atretic 31.5 f 6.7 31.5 f 3.2 19.3 f 2.5 30.3 6.6 1.0 k 0.7 11.0 k 3.1* 1.3 f 0.8 1.3 f 0.5 0 4.5 f 4.2 0.3 f 0.3 0.3 f 0.3 42.3 f 8.5 56.0 f 4.6 22.3 f 3.8 27.7 f 2.7 19.0 f 5.0 13.0 f 4.0 0.3 t 0.3 13.3 f 2.4* 0.3 f 0.3 1.3 f 0.9 0 0.7 f 0.3 0.3 f 0.3 0 34.5 f 3.8 61.3 f 10.1* 20.5 f 4.1 33.0 f 8.8 10.0 f 0.6 17.3 f 2.1* 2.3 k 1.0 8.8 f 3.0 1.0 f 0.4 1.5 f 0.6 0 0.3 f 0.3 0.8 f 0.5 0.5 k 0.3 49.0 t 8.5 60.4 f 9.4 26.6 k 5.1 31.8 f 5.0 18.6 f 4.2 12.8 f 3.1 2.8 f 1.2 8.4 f 1.7* 0.8 f 0.4 4.0 f 1.0* 0 1.0 k 0.8 0.2 f 0.2 1.8 f 0.8 48.3 f 6.8 50.5 f 6.8 28.0 f 4.9 21.5 3.2 18.8 f 2.8 12.8 f 2.9 0.5 t 0.5 11.3 f 0.9* 0.5 k 0.3 2.3 f 0.5* 0 2.5 f 2.5 0.5 f 0.5 0.3 t 0.3 50.0 f 2.5 57.7 f 4.1 28.0 f 4.2 29.0 f 1.7 20.7 f 2.0 22.7 f 4.6 0 4.3 f 2.2 1.0 f 0.0 1.3 f 0.7 0.3 f 0.3 0.3 f 0.3 0 0 50.7 f 14.7 59.3 f 15.0 30.0 f 7.6 25.3 k 6.6 16.3 t 7.7 17.0 f 5.3 0.3 f 0.3 6.7 k 1.9* 0.7 f 0.7 4.3 f 2.4 3.0 t 2.1 5.0 f 2.6 0.3 f 0.3 1.0 f 0.6 54.7 f 8.4 51.0 & 5.6 33.7 f 6.2 21.0 I 2 . 9 13.0 f 1.7 20.0 f 2.6 5.3 t 2.6 5.0 f 2.6 1.7 f 0.3 4.7 f 2.0 0.7 f 0.7 0.3 t 0.3 0.3 f 0.3 0 ~ + 'Number in parentheses is number of animals. *Significantly different from day 1 (P < .05). cervical vagotomy at 15 days. Gerendai and Nemeskeri (1983) reported that when right cervical vagotomy was combined with left ovariectomy, the weight of the remaining right ovary 48 days later was significantly less than that from animals with unilateral ovariectomy alone. Since there was a trend toward this in our study, perhaps a period longer than the 15 days after ULO is required for this effect. In contrast to cervical vagotomy, abdominal vagotomy a t the time of unilateral ovariectomy inhibited compensatory weight gain of both the left or right ovary 15 days later. This corroborates our previous studies (Burden and Lawrence, 1977) but is in contrast to the results of Sanders and Peppler (1982). These investigators maintained that abdominal vagotomy did not alter ovarian weight gain following ULO but did alter ovarian function in rats with both ovaries (Sanders and Peppler, 1982). In an earlier study, it was reported that abdominal vagotomy did not affect ovarian weight a t 15 days in rats with both ovaries intact (Burden and Lawrence, 1977). In the present study we report that abdominal vagotomy decreased ovarian weight a t 15 days in rats VAGOTOMY AND OVARIAN HYPERTROPHY with both ovaries intact. We offer the following explanation for these discrepant results: In the earlier study ovarian weights (average of 2 ovaries) were reported as mgI100 g body weight. In the present study, absolute ovarian weights, both left and right, are reported and the right ovary is heavier than the left in abdominally vagotomized rats. Also right ovarian weight of abdominally vagotomized rats is not significantly different from right ovarian weight of the sham group in the current study. We believe that the combination of averaging the weight of the right and left ovaries and expressing the results as mg/100 g body weight masked differences in ovarian weight attributable to vagotomy in the earlier study. In the current study, right cervical vagotomy and abdominal vagotomy produced seemingly disparate results in the remaining right ovary after ULO: compensatory ovarian hypertrophy was not significantly altered at 15 days, but follicular activation was reduced. It is generally believed that compensatory weight gain of the ovary remaining after ULO is caused by a n increased number of corpora lutea, resulting from a doubling of the number of follicles which ovulate (Peppler and Greenwald, 1970). Perhaps follicular activation did occur in the animals in the cycle immediately after ULO, but by 15 days, this response was attenuated, while ovarian weight was still elevated, because of the presence of older corpora lutea. Alternatively, perhaps follicular activation and compensatory ovarian hypertrophy may not be a cause and effect phenomenon. Nerves might participate in the process of follicular development without affecting the weight of the ovary. The loss of body weight following abdominal vagotomy has been reported by numerous workers (see review by Louis-Sylvester, 1983)and this effect has been employed by some investigators as a criterion for completeness of surgery (Clarkson et al., 1982). Because of this weight loss, the possibility of nonspecific effects of this surgery on ovarian function is always a question. In the present study, we evaluated selected parameters of the endocrine pancreas as a control because this organ is also innervated by the vagus nerve (Miller, 1981).Since the pancreas is involved in numerous metabolic processes, we felt the condition of this organ would reflect the generalized metabolic state of the animal. We found no differences in pancreatic weight, serum glucose, or insulin, nor in pancreatic hormone concentrations 15 days after abdominal vagotomy. Although we cannot rule out the possibility that abdominal vagotomy may affect pancreatic function over a longer time interval (e.g., 6-8 weeks), it would appear that the endocrine pancreas is less sensitive to this procedure than is the ovary. It is clear that the results obtained with the ovary are attributable to the vagotomy itself and not to the reduced weight loss, i.e., reduced metabolism, of the animal. Previous studies have also demonstrated that levels of high- and low-density lipoproteins were normal in abdominally vagotomized rats (Ojeda et al., 1983).Ovarian function is not altered in animals subjected to reduced food intake to mimic the body weight loss induced by vagotomy (Burden and Lawrence, 1977; Allen et al., 1983). Collectively, these observations suggest that altered ovarian functions subsequent to vagotomy are not nonspecific effects attributable to weight loss. Rather, 65 we believe the ovarian effects are caused, a t least in part, by interruption of specific vagal-ovarian nerves (Burden et al., 1983). The results of the current study indicate that neither left nor right cervical vagotomy nor abdominal vagotomy in rats bearing both ovaries preferentially alters left or right ovarian weight on day 15. In contrast, following left ULO, the data indicate that the compensatory follicular responses of the right ovary are facilitated by a n intact vagus nerve. Both right cervical vagotomy and abdominal vagotomy inhibited follicular activation in the right ovary after ULO. One might expect cutting the left cervical vagus to have no effect on ovarian function since this nerve contributes primarily to the anterior vagal trunk which innervates the liver, stomach, and pancreas (Hebel and Stromberg, 1976). In contrast, the right cervical vagus contributes primarily to the posterior vagal trunk, which goes into the celiac ganglion and is subsequently distributed to more caudal viscera (Niederhausern, 1953).Our data also show more large, healthy follicles in the right ovary in intact rats bearing both ovaries. This corroborates a n earlier observation of Buchanan (1974). Our data also suggests that function of the right ovary is more dependent than the left ovary on intact vagal connections. This difference is more obvious after left unilateral ovariectomy. We have demonstrated previously that nerves are involved in follicular development after ULO in guinea pigs (Curry et al., 1984).The mechanism by which nerves promote folliculogenesis after ULO is uncertain; however, the present study in rats indicates that follicular development after ULO in the right ovary, but not the left, is modulated by the vagus nerve. We hypothesize that right ovarian function is relatively more dependent on vagal innervation than left ovarian function. Experiments to test this hypothesis are currently in progress. ACKNOWLEDGMENTS The authors gratefully acknowledge the secretarial help of Sue Chapman. This work was supported by grant HD 06899 from the National Institute of Child Health and Human Development, United States Public Health Service. LITERATURE CITED Arai, H. (1920) On the cause of the hypertrophy of the surviving ovary after semi-spaying (albino rat) and on the number of ova in it. Am. J. Anat., 28:59-79. Aron, M., C. Aron, and J. 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