María Esther Cruz

Differences in the Ovulatory Ability Between the Right and Left Ovary Are Related to Ovarian Innervation

Peripheral innervation plays a role in the regulation of the function of the ovary. Both ovulation and endocrine functions can be modified by the alteration of ovarian innervation. Blockade or stimulation of ovarian nerves produce changes in ovarian function depending on the neural pathway and the experimental model used (1–3). Follicular development is modulated by catecholaminergic innervation, and the effects of its stimulation or blockade depends on the stage of follicular differentiation (4,5). Bilateral section of the vagus nerve induced an increase in the number of ova shed by the ovulating animal (2), while the same experiment performed in prepubertal animals induced a delay in puberty and in estrogen synthesis without changes in serum gonadotropin levels (6).

The role of the muscarinic system in regulating estradiol secretion varies during the estrous cycle: the hemiovariectomized rat model

There is evidence that one gonad has functional predominance. The present study analyzed the acute effects of unilateral ovariectomy (ULO) and blocking the cholinergic system, by injecting atropine sulfate (ATR), on estradiol (E2) serum concentrations during the estrous cycle. The results indicate that ULO effects on E2 concentrations are asymmetric, vary during the estrous cycle, and partially depend on the cholinergic innervation.Perforation of the left peritoneum resulted in lower E2 serum concentrations in the three stages of the estrous cycle. At proestrus, unilateral or bilateral perforation of the peritoneum resulted in lower E2 serum concentrations.ULO of the right ovary (left ovary in situ) resulted in significantly higher E2 concentrations than animals with ULO of the left ovary (right ovary in situ). ATR treatment to ULO rats on D1 resulted in a significant drop of E2 serum concentrations. ULO rats treated with ATR on D2 or P, resulted in an asymmetrical E2 secretion response; when the right ovary remained in situ an increase in E2 was observed, and a decrease when the left ovary remained in situ.The results obtained in the present study suggest that each ovarys ability to compensate the secretion of E2 from the missing ovary is different and varies during the estrous cycle. The results also suggest that the cholinergic system participates in regulating ovarian E2 secretion. Such participation varies according to the ovary remaining in situ and the stage of the estrous cycle of the animal.The results agree with previously stated hypothesis of a neural pathway arising from the peritoneum that participates in regulating E2 secretion, and also supports the idea of cross-talk between the ovaries, via a neural communication, that modulates E2 secretion.

Asymmetric effects of acute hemiovariectomy on steroid hormone secretion by the In situ ovary

The acute effects of hemiovariectomy on progesterone, testosterone, estradiol, and luteinizing hormone (LH) concentrations in serum were studied in rats under the following experimental conditions: control, sham-operated (left or right), hemiovariectomized, bilateral adrenalectomized, and hemiovariectomized plus bilateral adrenalectomized. One-hour after surgery, the concentration of progesterone and testosterone in the serum of right-side sham-operated rats was significantly higher than in control animals. Testosterone concentration in serum in rats with the right ovary in situ was higher than in sham-operated animals; injecting atropine sulfate 1 h before surgery blocked such increase, while the same treatment to rats with the left ovary remaining in situ resulted in a significant increase of testosterone concentration. Adrenalectomy resulted in an increase of testosterone concentration, which was higher when atropine sulfate was injected before surgery. Our results support the idea that left and right ovaries play different roles in the regulation of hormone secretion, and that such differences are related to ovarian innervation.

Endocrine profile following stimulation with recombinant follicle stimulating hormone and luteinizing hormone versus highly purified human menopausal gonadotropin.

BackgroundLuteinizing hormone (LH) activity in human menopausal gonadotropin (hMG) preparations is derived from human chorionic gonadotropin (hCG) rather than LH. Therefore, we aimed to determine whether there are similarities in the endocrine and follicular profiles of serum and follicular fluid from controlled ovarian stimulation with the recombinant gonadotropins follicle-stimulating hormone plus luteinizing hormone (rFSH + rLH) or highly purified human menopausal gonadotropin (HP-hMG).MethodsWe performed a prospective observational study with 50 oocyte donors that received either a combination of recombinant gonadotropins (rFSH + rLH) or a mixture of urinary gonadotropins (HP-hMG) plus purified urinary FSH (uFSH). Results were analyzed using Student’s t-test to compare continuous variables and the chi-squared test to compare proportions. P-values < 0.05 were considered statistically significant.ResultsAlthough more oocytes were retrieved after treatment with recombinant than urinary gonadotropins (16.5 vs. 11.8; P = 0.049), a higher proportion of metaphase II ova (71.2% vs. 80.6%; P = 0.003) were obtained using urinary gonadotropins. On day 6 and on the day of triggering, serum steroid hormone levels were slightly but not significantly elevated in the recombinant group compared with the urinary group. In follicular fluid, no statistical differences were observed for intra-follicular levels of steroid hormones between the two protocols; ongoing pregnancy rates were similar (46.1% vs. 46.1%).ConclusionsOur data suggest that endocrinological and follicular profiles do not differ between rFSH + rLH and HP-hMG stimulation.

Differential mRNA expression of alpha and beta estrogen receptor isoforms and GnRH in the left and right side of the preoptic and anterior hypothalamic area during the estrous cycle of the rat

Asymmetric mRNA expression was found in preoptic anterior and hypothalamic anterior areas of the two estrogen receptor isoforms and the gonadotropin-releasing hormone. On the right side of these areas, estrogen receptor alpha mRNA expression reached its peak on estrus day, while on the left side the peak was reached on proestrus day. Estrogen receptor beta mRNA expression peaked on both sides on the same day, diestrous-2 day, but at different hours, showing a sustained expression for the next measured hour on the left side, while peaking and dropping abruptly on the right side. Gonadotropin-releasing hormone also peaked on both sides on diestrous-2 day, being the left side peak expression significantly lower than the peak expression at the right side. The side expression differences suggest that different sides of the before mentioned areas may play different roles of endocrine reproductive functions, while differences of expression at different times may suggest interaction between sides for the same functions.

Differences in the ovulatory response to unilateral lesions in the preoptic or anterior hypothalamic area performed on each day of the estrous cycle of adult rats

The effects of a unilateral lesion made on the right or left side of the preoptic area (POA) or anterior hypothalamic area (AHA) made on each day of the estrous cycle, were analyzed. Ovulation rate decreased among the animals with a lesion performed on the day of estrous on the right side of POA (1/7 vs. 7/7, p < 0.05) and in animals with a lesion on diestrus-1 on each side AHA (4/9, 4/9 vs. 7/7, p < 0.05). Ovulation was restored by GnRH injection, while estradiol benzoate administration restored ovulation only in rats with a lesion on the right side of POA or AHA. We suggest that the participation of POA and AHA in the regulation of ovulation is asymmetric, lateralized, and changes during the estrous cycle. The estrogen-positive feedback needs the integrity of the left side of AHA on diestrus-1.

Ovulation delay induced by blockade of the cholinergic system on dioestrus-1, is related to changes in dopaminergic activity of the preoptic anterior-hypothalamic area of the rat

One hour after the injection of 100 mg/kg of atropine-sulphate at 1300 h of dioestrus-1, there was an abrupt increase of 17beta-oestradiol plasma level and a significant increase in dopaminergic neural activity in preoptic anterior-hypothalamic area, without changes in luteinizing hormone serum level, in comparison with the saline injected group. Animals injected with atropine-sulphate showed a second increase in dopaminergic neural activity in the preoptic anterior-hypothalamic at 1100 of dioestrus-2 (atropine-sulphate 0.471 +/- 0.7 vs. saline 0.241 +/- 0.03, p < 0.01). In this group of animals, the preovulatory surges of 17beta-oestradiol and luteinizing hormone occurred simultaneously at 1700 h of the expected day of oestrus; spontaneous ovulation was delayed until the expected day of dioestrus-1. Present results suggest that during dioestrus-1 there is a functional relationship between the cholinergic and dopaminergic systems in preoptic anterior-hypothalamic area, regulating the release of luteinizing hormone resulting in ovulation.

Ongoing pregnancy rates in intrauterine insemination are affected by late follicular-phase progesterone levels

OBJECTIVE To determine the relationship between serum P levels on the day of hCG administration and ongoing pregnancy rates. DESIGN Retrospective study. SETTING University-affiliated private IVF. PATIENT(S) A total of 2,458 couples undergoing IUI. INTERVENTION(S) Ovarian stimulation with human recombinant FSH. MAIN OUTCOME MEASURE(S) Ongoing pregnancy and miscarriage rates. RESULT(S) Progesterone concentrations were significantly higher given that the E2 concentration increased. Ongoing pregnancy rates were significantly decreased in women with P levels higher than 1.1 ng/mL; similar results were obtained in relation to miscarriage rates. CONCLUSION(S) Significant differences in ongoing pregnancy rates when P levels were elevated on the day of hCG administration may help clinicians to counsel patients about the reduced success rates with IUI and manage the timing of insemination to optimize implantation.

Differences in spontaneous ovulation in rats with unilateral lesion of the hypothalamus

The effects of unilateral lesion of the anterior (AH), median (MH) or posterior hypothalamus (PH) performed on diestrus 1, on ovulation and estrous cycle were analyzed in virgin rats. Only rats showing two consecutive estrous cycles of the same length were used. The lesion of AH decreased the ovulation rate (number of ovulating/number of treated rats) (14/26 vs. 24/24 of sham-operated group, p less than 0.01, Chi-square test), and the number of released ova per rat (5.0 +/- 1.1 vs. 10.3 +/- 0.8, p less than 0.05). Meanwhile, for ovulating animals no differences in the number of ova shed were observed. Lesions of the MH or PH did not modify the ovulation rate nor the number of ova shed. The left ovary of rats with MH and PH lesions, however, shed less ova than the left ovary of the control group (MH: 4.1 +/- 0.5; PH: 3.9 +/- 0.6; control: 5.7 +/- 0.5, p less than 0.05). These results suggest that neural information arising from the AH, MH or PH plays different roles in the regulation of ovulation.

Type of gonadotropin during controlled ovarian stimulation affects the endocrine profile in follicular fluid and apoptosis rate in cumulus cells.

OBJECTIVE To determine whether the type of gonadotropin affects the secretion of oocyte-specific factors, the endocrine pattern in follicular fluid, and the apoptosis rate in cumulus cells. STUDY DESIGN Prospective and observational study into an university-affiliated private in vitro fertilization setting. Ninety women included in our oocyte donation program were stimulated with human menopausal gonadotropin (hMG), recombinant follicle-stimulating hormone (FSH) or urinary FSH. Main outcome measures were growth-differentiation factor 9 (GDF-9) and bone morphogenetic protein 15 (BMP-15) expression, hormonal profile and apoptosis rate. RESULTS No statistically significant differences were observed for GDF-9 and BMP-15 among the three treatment groups. Estradiol concentrations in follicular fluid were significantly higher in women treated with hMG compared with recombinant FSH or urinary FSH. Testosterone levels were also higher in the group treated with hMG. A statistically significant association was found between the degree of apoptosis in cumulus cells and the type of gonadotropin. CONCLUSIONS The type of gonadotropin used during controlled ovarian stimulation significantly affects endocrine profiles in follicular fluid and the apoptosis rate in cumulus cells. However, there were no significant differences in the levels of oocyte-secreted factors between treatments.