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R. Domínguez

ABSTRACT

Differences were observed in the ovulation rates of the right and left ovaries in response to unilateral lesions of the cervico-vaginal plexus (CVP) followed by pseudopregnancy or by anaesthesia of the CVP induced with panthocaine plus adrenaline (right ovary 6·7±0·4 (s.e.m.) vs left ovary 4·6 ± 0·9; P<0·05). Pseudopregnancy (days showing a dioestrous smear after copulation with a vasectomized male before an oestrous smear following a pro-oestrous one) lasted longer in rats with a lesion in the CVP than in a control pseudopregnant group (14·9 ± 0·5 vs 11·2 ± 0·5; P < 0·01). Anaesthesia of the CVP performed on each day of the oestrous cycle did not modify the ovulation rate compared with laparotomized animals. Both laparotomy and anaesthesia of the CVP performed on oestrus or day 1 of dioestrus blocked ovulation but when they were performed on day 2 of dioestrus or pro-oestrus they failed to do so (laparotomy 9/18 vs 12/14, P<0·05; anaesthesia of CVP 3/11 vs 17/17, P < 0·05). The number of ova shed by the left ovary in animals with anaesthetized CVP was lower than by the right ovary (4·5 ± 0·6 vs 6·2 ± 0·5; P<0·05). These results add further support to the idea that the CVP participates in the regulation of ovulation rate, and that the left ovary is less adaptable than the right when innervation is challenged.

Journal of Endocrinology (1990) 124, 43–45

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R Chávez and R Domínguez

Abstract

The effects were analysed of section of the superior ovarian nerve on compensatory ovulation and ovarian hypertrophy, in adult rats with the left or right ovaries extirpated during the oestrous cycle and autopsied 6 or 20 days later. Rats with hemiovariectomy or hemiovariectomy plus denervation recovered their oestrous cyclicity between 2 and 3 days after surgery. Six days after hemiovariectomy 14 out of 17 rats ovulated on the expected day of oestrus. All the animals were hemiovariectomized on the day of pro-oestrus. The mean ± s.e.m. number of ova shed was similar to the group of animals with both ovaries (7·8 ± 1·2 vs 9·5 ± 0·2 Compensatory ovarian hypertrophy was observed in the right ovary when left hemiovariectomy was performed on day 2 of dioestrus or pro-oestrus; similar results were observed in the left ovary when the right one was extirpated at oestrus or pro-oestrus. Section of the right superior ovarian nerve in left-hemiovariectomized rats caused a reduction in ovulation rate and number of ova released. Compensatory ovarian hypertrophy was modified in the opposite way by unilateral section of the superior ovarian nerve to the in situ ovary depending on the day of the cycle when hemiovariectomy was performed. Twenty days after treatment, ovulation rate, compensatory ovulation and ovarian hypertrophy were similar in both left- or right-hemiovariectomized rats. Compensatory ovarian hypertrophy increased in all animals with section of the superior ovarian nerve, except when hemiovariectomy was carried out at oestrus or the left ovary was extirpated on day 1 of dioestrus. The results suggest that modulation of compensatory ovarian hypertrophy by neural information arriving at the ovary by way of the superior ovarian nerve varies during the oestrous cycle.

Journal of Endocrinology (1994) 140, 197–201

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A. Flores and R. Domínguez

ABSTRACT

The noradrenergic innervation of the ovary of prepubertal rats causes an inhibitory response of the follicles to gonadotrophins, leading to ovulation. We investigated the possibility that noradrenergic peripheral denervation at birth, produced by treatment with guanethidine, modifies the positive feedback effects of gonadotrophins and oestradiol in prepubertal rats, and also the possibility that peripheral denervation can modify the anovulatory syndrome induced by androgenization at birth.

Noradrenergic peripheral denervated rats of 18 days of age treated with pregnant mare serum gonadotrophin (PMSG) ovulated 96 h later, while normal animals did not ovulate (4/9 vs 0/12, P < 0·05) and the number of ova shed was lower than in rats which ovulated spontaneously at first vaginal oestrus (3·5 ± 0·6 vs 8·3 ± 0·4 (s.e.m.), P < 0·01). Oestradiol benzoate (10 μg) did not induce ovulation in either normal or denervated animals (0/11 and 0/11). The anovulatory syndrome induced by the administration of testosterone propionate (75 μg) at birth was partially blocked by noradrenergic peripheral denervation (4/7 ovulated vs 0/10).

The results suggest that some neural information arising from the ovary modulates, in an inhibitory way, the stimulatory feedback mechanisms required to induce ovulation. Partial inhibition of the anovulatory syndrome resulting from androgenization caused by peripheral noradrenergic denervation suggests that noradrenergic neural information sent by the ovary to the hypothalamus results in a decreased concentration of noradrenaline in the hypothalamus and in the aromatization of androgens to oestrogens.

Journal of Endocrinology (1992) 135, 415–420

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R. Chávez, M. E. Cruz and R. Domínguez

ABSTRACT

The possible existence of peripheral asymmetry in the neuroendocrine mechanisms participating in the response of the ovary to gonadotrophins, and the participation of the vagus nerve, was investigated. At oestrus, the ovulation rate (number of ovulating/number of treated rats) of the left ovary in right unilaterally ovariectomized rats was lower than that in the right ovary in left unilaterally ovariectomized rats (42 vs 84%). No differences in the number of ova shed per ovulating animal nor in compensatory ovarian hypertrophy (COH) were observed. Bilateral section of the vagus nerve resulted in reduced COH only in those animals with the left ovary in situ (right unilaterally ovariectomized). Section of the left vagus nerve induced different effects depending upon which ovary was left in situ. When the left ovary was in situ an increase in ovulation rate, COH and number of ova shed was observed; however, when the right ovary was left in place the above three parameters decreased. Section of the right vagus nerve produced a decrease only in COH in both right and left unilaterally ovariectomized animals. It is concluded that in the unilaterally ovariectomized rat the right ovary seems more able to react to compensatory regulatory systems than does the left. The character of the information carried by the left and right vagus nerve is different.

J. Endocr. (1987) 113, 397–401

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M. E. Cruz, J. Castro and R. Domínguez

ABSTRACT

The effects were analysed of a unilateral implant of atropine on ovulation in intact and hemiovariectomized adult rats, together with the response of the atropine-implanted rats to hormone replacement. An outer cannula directed to the left or right preoptic (POA)-anterior-hypothalamic area (AHA) was implanted into cyclic adult rats. A group of animals in oestrus was hemiovariectomized and some were also implanted with a cannula. After two consecutive 4-day cycles, the hemiovariectomized animals were implanted with atropine (23 ± 4 μg) or cholesterol (25 ± 2 μg) on the day of oestrus. Atropine implanted into the left side of the POA-AHA blocked ovulation and compensatory ovarian hypertrophy, whilst implants in the right side had no effects. Administration of gonadotrophin-releasing hormone (GnRH; 3·7 μg/kg) at 13.00 h on the expected day of pro-oestrus induced ovulation in six out of seven treated animals. Of 19 rats with an implant of atropine in the left side of the POA-AHA, one ovulated after treatment with pregnant mare serum gonadotrophin (PMSG) on oestrus, or oestradiol benzoate or human chorionic gonadotrophin (hCG) on day 2 of dioestrus. The effects on ovulation of a unilateral implant of atropine into the POA-AHA of cyclic adult rats and the responses of such rats to GnRH, PMSG, hCG and oestradiol benzoate replacement were also studied. Ovulation was induced in rats with a unilateral implant of atropine and which had been treated with GnRH or hCG at 13.00 h on the expected day of pro-oestrus after the implant. In rats with an atropine implant, treatment with PMSG on the day of implantation or with oestradiol benzoate on day 2 of dioestrus restored ovulation in those with the implant in the left side of the hypothalamus, but was ineffective in those with the implant in the right side. The results suggested that in the adult rat the muscarinic mechanisms regulating preovulatory GnRH release, as well as the stimulatory effects of oestrogen, are lateralized. As the results observed in intact and hemiovariectomized animals subjected to the same treatments were different, it was concluded that the cholinergic neuroendocrine mechanisms regulating ovulation are related to the neural information arising from the ovaries and reaching the POA-AHA.

Journal of Endocrinology (1992) 133, 205–210

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L Hinojosa, R Chavira, R Dominguez and P Rosas

The effects of thymulin administration beginning on days 19 or 24 of age on spontaneous puberty and gonadotrophin-induced ovulation were analysed in female normal and hypothymic mice. In normal and hypothymic mice, the daily administration of thymulin at 24 days of age resulted in a delay in the age of vaginal opening, with an increase in serum progesterone levels. Normal mice treated with 200 ng thymulin beginning on day 19 of age and injected with pregnant mare serum gonadotrophin (PMSG) 24 h later had an increase in ovulation rate, number of ova shed and weight of the ovaries. None of the hypothymic mice treated with thymulin on day 19 and PMSG on day 20 ovulated. PMSG treatment on day 25 induced ovulation in hypothymic mice. When these animals were injected previously with 200 ng thymulin, the number of ova shed by ovulating animals was lower than in PMSG-treated animals. Administration of thymulin and sequential injection of PMSG and human chorionic gonadotrophin 54 h later resulted in an increase in ovulatory response in comparison with those receiving only PMSG. The results suggest that thymulin plays a role in the regulation of spontaneous puberty through its effects on adrenal and ovarian endocrine functions. The increase in the ovarian PMSG response-treated animals, previously given thymulin, showed that this thymic hormone participates in the regulation of gonadotrophin secretion mechanisms and seems to be dose- and age-dependent. In hypothymic mice, neuroendocrine mechanisms regulating puberty are different from those of normal mice.

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L Riboni, C Escamilla, R Chavira and R Dominguez

The effects of peripheral sympathetic denervation induced by guanethidine administration to newborn and 10-day-old female guinea pigs on puberty, ovulation and the follicular population were analysed. Peripheral sympathetic denervation beginning at birth resulted in the loss of ovarian norepinephrine content (0.95. +/- 0.1 ng/mg wet tissue in untreated control animals vs non detectable in treated animals). Guanethidine administration to newborn or 10-day-old guinea pigs advanced puberty (age of vaginal opening: 27 +/- 1.2 days (newborn), 26 +/- 1.7 (10-day-old) vs 37 +/- 0.7 (control), P < 0.001) and ovulation. The number of corpora lutea in control and denervated animals was similar (3.5 +/- 0.2 vs 3.3 +/- 0.3). The relative weight (mg/100 g body weight) of the ovaries and adrenals in the denervated animals autopsied during the late follicular phase (24-48 h after vaginal opening) increased (ovaries: 27.8 +/- 1.3, 28.9 +/- 3.0 vs 20.9 +/- 0.8, P < 0.05; adrenals 36.4 +/- 1.4, 37.0 +/- 0.8 vs 31.6 +/- 1.5, P < 0.05), while the uterine weight diminished (179 +/- 13, 149 +/- 28 vs 292 +/- 20). When the animals were killed during the late luteal phase (9-11 days after vaginal closure), the relative weight of the ovaries of newborn guanethidine-treated animals was higher than that of the control animals (21.4 +/- 1.7 vs 16.8 +/- 1.4, P < 0.05). The mean number of follicles counted in the ovaries of denervated animals was significantly higher than in control animals (1736 +/- 230 vs 969 +/- 147, P < 0.05). The mean diameter of the follicles in the untouched control ovary in animals killed in the late follicular phase was significantly larger than from animals killed in the late luteal phase (263 +/- 3.9 microns vs 248 +/- 3.0 microns, P < 0.01). The mean diameter of the follicles measured in the ovaries of denervated animals was significantly higher than in controls (animals treated from birth 274 +/- 2.0 microns vs 255 +/- 2.4, P < 0.05; animals treated from day 10, 286 +/- 2.3 microns vs 257 +/- 2.3, P < 0.05). When the mean diameter of the follicles in the left and right ovary of the untouched control was analysed, the follicular diameter in the left ovary was significantly larger than in the right ovary (309 +/- 6.0 microns vs 214 +/- 3.9, P < 0.01); the response of the left and right ovaries to sympathetic denervation was the opposite. The results obtained in the present study suggest that ovarian innervation plays a role in the regulation of follicular growth, maturation and atresia which is not related to changes in steroid secretion by the ovary, but to other regulatory mechanisms.

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R. Chávez, S. Sánchez, A. Ulloa-Aguirre and R. Domínguez

ABSTRACT

The effects of unilateral section of the right or left vagus nerve (SRVN, SLVN) performed on different days of the oestrous cycle of the rat were analysed. Vagal nerve section on the day of oestrus or on day 1 of dioestrus (D1) altered oestrous cyclicity in a more significant way than when it was performed on day 2 of dioestrus (D2) or pro-oestrus (6/58 maintained normal oestrous cycles compared with 32/39 that did not; P<0.01). Ovulation rate at oestrus was lower in rats with SLVN than in the sham-operated group (32/47 vs 28/32; P < 0.05). The number of ova shed by the left ovary was reduced in sham-operated rats and in animals with SRVN and SLVN, whereas the number shed by the right ovary was not modified. The day of the oestrous cycle on which the vagus nerve was cut also influenced the number of ova shed. No changes in plasma levels of FSH at oestrus were observed in animals with SRVN or SLVN. The results indicate that vagal manipulations performed at the beginning of the oestrous cycle (day of oestrus and D1) induce more changes on oestrous cyclicity and ovulation than when they are performed during the second half of the cycle (D2 and pro-oestrus). In addition, the left ovary is more sensitive to neural manipulation than is the right one.

Journal of Endocrinology (1989) 123, 441-444

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L Garcia, L Hinojosa, R Dominguez, R Chavira and P Rosas

The effects of thymectomy performed on 10-day-old (Tx-10) mice on spontaneous puberty and the ovulatory response induced by gonadotrophin treatment were analysed, together with the effects of thymulin replacement from 10 days of age. Infantile thymectomy induced a delay of puberty, a decrease in serum 17beta-oestradiol concentration and a reduced total number of follicles. Injection of thymulin (12 ng/g body weight) to Tx-10 mice resulted in an earlier onset of puberty, a decrease in the weights of ovaries and uterus, and an increase in serum 17beta-oestradiol concentrations. In control and Tx-10 mice, treatment with pregnant mare serum gonadotrophin (PMSG) (5 IU) at 25 days of age resulted in ovulation and the numbers of ova shed by ovulating animals were similar. When the animals were injected with 1 IU PMSG ovulation did not occur. In Tx-10 mice, both 1 and 5 IU PMSG increased the number of follicles to values similar to those observed in the controls. In Tx-10 mice the sequential injection of PMSG (1 IU) and human chorionic gonadotrophin (hCG) (3 IU) resulted in ovulation, but the number of ova shed was lower than in controls. When these animals were injected daily with thymulin, an increase in the number of ova shed and serum 17beta-oestradiol concentrations was observed. The uterine weight of Tx-10 mice was always significantly reduced in response to gonadotrophin treatment. Thymulin injection in PMSG-hCG-treated Tx-10 mice provoked a significant increase in uterine weight. The results suggest that the presence of the thymus after the neonatal period is necessary to normal ovarian development and function. The increase in gonadotrophin-induced ovarian response produced by thymulin replacement indicates that this peptide has a role in this process as one of the connecting signals between thymus and ovaries.

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L Morales, R Chavez, ME Ayala and R Dominguez

The modulating effects of ovarian innervation reaching the ovary through the suspensory ovarian nerve on the reactivity of the ovaries to gonadotrophins were analysed. Juvenile rats (32 days old), with or without unilateral or bilateral section of the superior ovarian nerve, were injected with 8 iu of pregnant mare serum gonadotrophin (PMSG), 10 iu of human chorionic gonadotrophin (hCG) or with 8 iu of PMSG followed 56 h later with 10 iu of hCG. Treatments were given immediately after surgery or 4 days later, and the rats were killed on the day of first vaginal oestrus. In rats with unilateral section, treatment with PMSG did not induce full ovulatory response by the denervated ovary whether the treatment was applied immediately or 4 days after surgery (0/11 rats treated immediately ovulated vs 5/5 (sham) and 11/12 (control, P < 0.05 Fisher's exact probability test), and 4/19 did when treatment was done 4 days after surgery vs 8/10 (sham) and 11/12 (control, P < 0.05). The rats with bilateral section receiving the same hormonal treatment, PMSG administration, ovulated. The number of ova shed by the left ovary was similar to those of the control, while the right ovary released fewer ova. Stimulation with hCG immediately after unilateral section did not induce ovulation in normal or denervated ovary. When the treatment was applied 4 days after surgery, ovulation was observed only in the innervated ovary. In the rats with bilateral section, hCG injection induced ovulation in both ovaries. In those rats with unilateral section of the superior ovarian nerve, the treatment with PMSG + hCG given immediately after surgery resulted in a compensatory ovulation by the innervated ovary (the number of ova shed/ovulating animal was significantly higher than those released by control or sham-operated animals: left section, number of ova shed by the right ovary 7.6 +/- 0.3 vs 5.5 +/- 0.8 and 4.9 +/- 1 respectively, P < 0.05; right section, number of ova shed by the left ovary 10.2 +/- 0.6 vs 4.4 +/- 1.1 and 7.0 +/- 0.9, P < 0.05), while the denervated one showed a lower ovulation rate as well as a smaller number of ova shed than those by the control animals. When the hormonal replacement was given 4 days after surgery, such compensatory ovulation was observed in the left ovary of those rats with a section of the right nerve (14.3 +/- 2.6 vs 4.4 +/- 1.1 and 6.5 +/- 1.1, P < 0.05). When the PMSG + hCG treatment was applied to animals with bilateral section of the superior ovarian nerve, the ovulation rate by the right ovary was significantly lower than in control and sham-operated treated animals (2/10 vs 11/11 and 6/7, P < 0.05). Because the ovaries receive innervation through the superior ovarian nerve, the ovarian plexus and the vagus nerve, the results obtained in unilateral denervated animals suggest that the innervation of the ovary via the superior ovarian nerve regulates in a stimulatory way the effects of gonadotrophin resulting in ovulation. The ovulation induced by hormonal treatment of rats with bilateral section of the superior ovarian nerve suggests that the effects of bilateral section on ovulation are not the addition of the effects of left and right denervation, implying the existence of a modulatory effect in gonadotrophin action on ovulation via other neural pathways.