Inhibition Of Follicular Development Research Articles

Impairment of ovarian follicular development caused by titanium dioxide nanoparticles exposure involved in the TGF-β/BMP/Smad pathway.

Titanium dioxide nanoparticles (TiO2 NPs) have been shown to induce reproductive system damages in animals. To better underline how TiO2 NPs act in reproductive system, female mice were exposed to 2.5, 5, or 10mg/kg TiO2 NPs by gavage administration for 60 days, the ovary injuries, follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels as well as ovarian follicular development-related molecule expression were investigated. The results showed that TiO2 NPs exposure resulted in reduction of ovary weight and inhibition of ovarian follicular development. Furthermore, the suppression of follicular development was demonstrated to be closely related to higher FSH and LH levels, and higher expression of activin, follistatin, BMP2, BMP4, TGF-β1, Smad2, Smad3, and Smad4 as well as decreased inhibin-α expression in mouse ovary in a dose-dependent manner. It implies that the impairment of ovarian follicular development caused by TiO2 NPs exposure may be mediated by TGF-β signal pathway.

Maternal exposure to cadmium from puberty through lactation induces abnormal reproductive development in female offspring

Four-week-old female ICR mice were exposed to Cd through drinking water from puberty through lactation to investigate the effects of reproductive development in female offspring. Our results showed that maternal Cd exposure from puberty to lactation induced vaginal opening delay, and disturbed estrous cycle in the offspring on postnatal day (PND) 21, without affecting the body weight at vaginal opening. The histopathology results showed the increased primordial follicles and the decreased secondary follicles, and the mRNA level of Amh increased in the offspring’s ovaries upon Cd exposure, suggesting the inhibition of ovarian follicular development on PND21. Moreover, the level of serum estradiol reduced and genes associated with steroidogenesis (3β-Hsd, P450scc and P450arom) were downregulated upon Cd exposure on PND 21. Thus, Cd may inhibit the follicular development via disturbing the mRNA level of genes associated with steroidogenesis and then the synthesis of estradiol in prepuberty. Taken together, despite the lack of attention to estrous cycle at termination, maternal Cd exposure from puberty to lactation induced the adverse effects on reproductive development of female offspring, including the delay of vaginal opening, irregular estrous cycle and inhibition of follicular development, via disturbing the mRNA level of genes associated with follicular development and steroidogenesis.

EVALUATION METABOLIC SYNDROME IN POLYCYSTIC OVARIAN SYNDROME IN REPRODUCTIVE AGE GROUP WOMEN

Background: The disorder can be morphological (polycystic ovaries) or predominantly biochemical (hyperandrogenemia). Hyperandrogenism, a clinical hallmark of PCOS, can cause inhibition of follicular development, microcysts in the ovaries, anovulation, and menstrual changes
 Objectives: To study the risk factors for developing metabolic syndrome in PCOS.
 Material and Methods: This is Prospective study, total 100 patients, department of obs and Gynae, women of reproductive agegroup (15-45yrs) attending OPD at Darbhanga medical college and Hospital Laheriasarai, Bihar. Conclusion: This study helps in recognition of this high-risk group and aid in the enforcement of preventive strategies including therapeutic lifestyle modificationsand risk factor management. This will have a promising impact on women’s health and will prevent or delay the outset of varyingcardiometabolic complications in PCOS.
 Keywords: PCOS, metabolic syndrome

Androgens as double-edged swords: Induction and suppression of follicular development.

Androgens, which are mediated via the androgen receptor (AR), play important roles in normal follicular development and female fertility. However, just like a double-edged sword, besides the positive effects of androgen on follicular development, abnormal androgen levels, especially as in hyperandrogenism, seriously suppress normal follicular development. A crucial balance exists between the importance of androgens in follicular development and their negative effects when in excess. As the first meiotic division and epigenetic reprogramming are two critical events in oogenesis, abnormal androgen levels or deficiency in androgen/AR signaling in the ovary may affect these vital events. Oocytes have a tendency to develop genomic instability, thus resulting in an increasing incidence of unpredictable adult diseases. Although many studies have explored the effects of androgens and AR on follicular development, the conclusions are controversial and there has been no thorough review of this topic. This review focuses on the roles of androgens in the physiological process of follicular development, summarizes new insights into the roles of androgens in the arrested development of follicles, and discusses the potential risk of adult diseases originating from abnormal follicular androgen levels or androgen receptor signals, which may determine areas for future studies.

Combined hormonal contraceptive use is associated with lower serum antimullerian hormone levels

There are conflicting reports of the effect of oral contraceptive use on serum AMH. Recent publications suggest hormonal contraception decreases the AMH produced by granulosa cells of the early growing follicles through inhibition of follicular development. We investigated the effect of combined hormonal contraceptives on AMH levels in an oocyte donor population.

Impact of body mass index on suppression of follicular development and ovulation using a transdermal patch containing 0.55-mg ethinyl estradiol/2.1-mg gestodene: a multicenter, open-label, uncontrolled study over three treatment cycles

BackgroundBody mass index (BMI) may influence ovulation inhibition resulting from transdermal hormone delivery. Investigation of this effect is important given the high prevalence of obesity in the US. Study DesignThis open-label, uncontrolled, Phase 2b trial stratified 173 women (18–35 years) according to three BMI groups (Group 1, n=56, ≤30kg/m2; Group 2, n=55, >30kg/m2 and ≤35kg/m2; and Group 3, n=47, >35kg/m2). Women used a contraceptive patch containing 0.55-mg ethinyl estradiol (EE) and 2.1-mg gestodene (GSD). The EE/GSD patch was used weekly for three 28-day cycles (one patch per week for 3 consecutive weeks followed by a 7-day, patch-free interval), and its effect on ovulation was assessed by the Hoogland score, a composite score that comprises transvaginal ultrasound and estradiol (E2) and progesterone levels every 3days in Cycles 2 and 3. Evaluation of pharmacokinetic parameters was a secondary aim of the study, and blood samples for analytic determination of EE, GSD and sex hormone-binding globulin were taken during the pretreatment cycle, Cycle 2 and Cycle 3. Compliance was assessed using diary information and serum drug levels. ResultsIn the per-protocol set, there were only six ovulations during the study, and no participant ovulated in both study cycles. One ovulation occurred in Group 1, three in Group 2 and two in Group 3. Ovulation inhibition was unaffected by BMI; in all groups, most participants had Hoogland scores of 1 or 2 (i.e., follicle-like structures <13mm: Group 1, ≤30kg/m2, 80.0% in Cycle 2, 85.7% in Cycle 3; Group 2, >30kg/m2 and ≤35kg/m2, 61.4% in Cycle 2, 75.0% in Cycle 3; Group 3, >35kg/m2, 78.0% in Cycle 2, 72.5% in Cycle 3). Serum levels of follicle-stimulating hormone, luteinizing hormone, E2 and progesterone were similar between groups. Body weight had a limited effect on EE clearance that was unlikely to be clinically relevant. ConclusionThe EE/GSD patch provided effective ovulation inhibition, even in women with higher BMI. ImplicationsThis is the largest-to-date study of physiologic endpoints and found no clinically important differences in ovarian suppression among obese and normal-weight users of the EE/GSD contraceptive patch, thus providing reassurance that obese women can achieve the same high level of contraceptive protection as normal-weight users.

Benzo[a]pyrene Inhibition of Follicular Development and Survival Is Associated with Dysregulation of Hsp90, Bax, CYP1A1, and CYP1B1 Expression.

Benzo[a]pyrene Inhibition of Follicular Development and Survival Is Associated with Dysregulation of Hsp90, Bax, CYP1A1, and CYP1B1 Expression.

Studies on the protective effects of pollen-originated phytoestrogens on the growth and development of ovary in rats

This present study was undertaken to investigate the effects of pollen extracts on the development of ovary in the presence of exogenous estradiol benzoate. 45-day old female Wistar rats were administered with estradiol benzoate to induce the pathological status of the ovary. Histological observation of ovarian paraffin sections revealed that interruption of the maturation of follicles was associated with massive follicular atresia. Significantly increased serum FSH level was characteristic of the rats. Exposing to estradiol benzoate also resulted in severe lesion of the liver. Abnormally elevated levels of alanine aminotransferase and aspartate aminotransferase were accompanied by increased liver weight and hepatosomatic index. Extracts of phytoestrogens from pollen exhibited protective effects on ovary and liver tissues. Histological evaluation showed that the inhibition of follicular development was markedly diminished after receiving treatment for 28 days. Serum FSH concentration was restored to the normal level. No significant difference in ovarian weight and ovary-somatic index could be detected between treated groups and the control group. The liver tissue displayed normal morphology and function. Taken together, our results demonstrated pollen-originated phytoestrogens were helpful in re-establishing the hormonal milieu and attenuating the adverse influences of estradiol benzoate on the ovary and liver tissues. Key words: Estradiol benzoate, phytoestogen, pollen, ovary, liver.

A chewable low-dose oral contraceptive: a new birth control option?

A new chewable combined oral contraceptive pill containing ethinyl estradiol (EE) 0.025 mg and norethindrone (NE) 0.8 mg in a 24/4 regimen was approved for marketing in December 2010. Each of the four inactive tablets contains 75 mg ferrous fumarate, which has no therapeutic benefit. The tablet can be taken with food but not water as this affects the absorption of EE. The Pearl index based on intention to treat women aged 18–35 years has been reported at 2.01 (confidence interval [CI] 1.21, 3.14) and for the whole population 1.65 (CI 1.01, 2.55). The effect of a body mass index of >35 was not studied. Regular withdrawal bleeding occurred for 78.6% of women in Cycle 1, but by Cycle 13 almost half the women failed to have a withdrawal bleed. This new formulation provides an intermediate dose of an EE/NE combination that will be useful for women experiencing breakthrough bleeding on the lower-dose EE/NE pill. The convenience of a low-dose pill, which can be chewed without the need for water, will be useful to enable women who have forgotten a pill to take one whenever they remember, provided they carry it with them. The advantage of a 24/4 regimen is better suppression of follicular development in the pill-free interval and may be beneficial for women who experience menstrual cycle-related problems, such as heavy bleeding or dysmenorrhea.

Evaluation of ovarian toxicity of mono-(2-ethylhexyl) phthalate (MEHP) using cultured rat ovarian follicles

Mono-(2-ethylhexyl) phthalate (MEHP) is the most toxic metabolite of di-(2-ethylhexyl) phthalate (DEHP). It has been reported that DEHP causes abnormal reproductive development in women, and suppresses estradiol synthesis and ovulation in female rats with diminished size of preovulatory follicles. The present study was conducted to evaluate the ovarian toxicity of MEHP using cultured rat ovarian follicles. Secondary follicles were isolated from the ovaries of 14-day-old female rats and cultured for 48 hr with MEHP (0, 10, 30, and 100 µg/ml). At 0, 24, and 48 hr of MEHP treatment, follicular diameters were measured. After the culture, viability and apoptosis of follicles were assessed, and progesterone, androstenedione, testosterone, and estradiol levels in culture media were measured. At 100 µg/ml, suppression of follicular development was observed, which is associated with decreased viability of follicles and apoptosis of granulosa cells. At this concentration, progesterone level increased markedly, whereas androstenedione, testosterone, and estradiol levels decreased. At 10 and 30 µg/ml, follicular development was not suppressed, no apoptotic change was observed, and the levels of all measured steroid hormones tended to increase. The combined levels of all steroid hormones increased at all concentrations of MEHP, and the increase implies that MEHP activates the synthetic pathway from cholesterol to estradiol including de novo synthesis of cholesterol. However, the progesterone/androstenedione ratio increased extremely at 100 µg/ml, and the increase implies that MEHP inhibits the conversion of progesterone to androstenedione. In conclusion, MEHP induces ovarian toxicity via suppression of follicular development and abnormal steroid hormone synthesis in cultured rat ovarian follicles.

Evaluation of ovarian toxicity of sodium valproate (VPA) using cultured rat ovarian follicles

Sodium valproate (VPA) is a major antiepileptic drug that is widely used for the treatment of epilepsy as well as other neuropsychiatric diseases. The present study was conducted to evaluate the ovarian toxicity of VPA using cultured rat ovarian follicles. Secondary follicles were isolated from the ovaries of 14-day-old female rats and cultured for 48 hr with VPA (0, 0.2, 1.0, and 5.0 mM). At 0, 24, and 48 hr of VPA treatment, follicular diameters were measured. After the culture, viability of follicles and expression of aromatase in the follicles were assessed, and progesterone, androstenedione, testosterone, and estradiol levels in culture media were measured. At all concentrations of VPA, follicular development was suppressed, and androstenedione, testosterone, estradiol, and combined levels of all steroid hormones tended to decrease in association with suppression of aromatase expression in granulosa cells. Additionally, the suppression of follicular development was associated with decreased viability of follicles and an increased progesterone level at 5.0 mM of VPA. The decrease in the combined levels of all steroid hormones implies that VPA suppresses the synthetic pathway from cholesterol to estradiol including de novo synthesis of cholesterol. In conclusion, VPA induces ovarian toxicity via suppression of development and abnormal steroid hormone synthesis in cultured rat ovarian follicles.

509. REGULATING MURINE FOLLICLE DEVELOPMENT BY STIMULATION OF THE JAK2/STAT3 SIGNAL TRANSDUCTION PATHWAY

Follicular development requires the recruitment of primordial follicles into the growing follicle pool following initiation of multiple cytokine signalling pathways. Suppression of follicular development is thought to be key to maintaining the population of primordial follicles and allowing for controlled release of these follicles throughout the reproductive lifespan of the female. However, little is known of the processes and signalling molecules that suppress primordial follicle activation and early follicle growth. Our group has identified significant upregulation of the Janus Kinase 2 (JAK2)/ Signal Transducer and Activator of Transcription 3 (STAT3) signalling pathway inhibitor the Suppressor of Cytokine Signalling 4 (SOCS4) that coincides with the initial wave of follicular activation in theneonatal mouse ovary. Further studies by our group have localised the SOCS4 protein to the granulosa cells of activating and growing follicles, suggesting SOCS4 expression may be linked to follicular activation. We have focused on examining protein localisation and gene expression patterns of the eight SOCS family members CIS and SOCS1-7. We have recently demonstrated that co-culture of neonatal ovaries with Kit Ligand (KL) for 2 days increases the mRNA levels of all SOCS genes. We also demonstrated the co-localisation of SOCS2 proteins with the KL receptor c-kit in the mural granulosa cells of antral, and large pre-antral follicles suggesting a significant role for SOCS2 in the later stages of follicular development. We have also shown that culturing ovaries with the potent JAK2 inhibitor AG490 substantially reduces mRNA levels of all SOCS and STAT genes that we have so far measured. We hypothesise a significant role for JAK2/STAT3 signalling in promoting the activation and early growth of ovarian follicles. Our investigations have identified significant roles for JAK2/STAT3 and the SOCS family in the regulation of ovarian follicle development.

Inhibition of Follicular Development, Vitellogenesis, and Serum 17β-Estradiol Concentrations in Zebrafish Following Chronic, Sublethal Dietary Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin

The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent endocrine disruptor with the ability to affect several biologic processes, including reproduction. In fish, sublethal exposure to TCDD is known to modulate overall reproductive capacity, but impacts on follicular development and vitellogenesis are unknown. Here we show that chronic, dietary exposure to 0.08, 0.32, or 0.80 ng TCDD female(-1) day(-1) decreased egg production by more than 50% and that spawning success was reduced by as much as 96%. Serum estradiol concentrations were decreased more than twofold, accounting, in part, for observed decreases in serum vitellogenin concentrations by as much as 29%. Our data suggest that decreased egg production is likely the result of TCDD-mediated inhibition of the transition from pre-vitellogenic stage follicles to vitellogenic stage follicles, as well as the induction of follicular atresia. The majority of reproductive toxicity of TCDD is likely due to direct impacts on the ovary, yet histopathologic observations suggest liver toxicity could also contribute to observed impacts on vitellogenesis. Importantly, even when overall egg production is not significantly affected, our data show that subtle physiologic changes induced by TCDD can lead to altered gonadogenesis. This suggests that long-term exposure to very low concentrations of TCDD could greatly affect fecundity and reproductive success in fishes.

Vascular endothelial growth factor receptor 2–mediated angiogenesis is essential for gonadotropin-dependent follicle development

Gonadotropins induce ovarian follicle growth that is coincident with increased follicular vasculature, suggesting a role of angiogenesis in follicle development. Functional studies performed in nonhuman primates show that administration of substances that inactivate VEGF block the development and function of preovulatory follicles as demonstrated by histological analysis or hormone measurements. Blockage of function of VEGF receptor 2 (VEGFR-2) alters follicular hormone secretion, suggesting that the intraovarian effect of VEGF might be mediated by this receptor. The specific mechanism by which follicular development was blocked in these previous studies remains unclear, however. Here we characterize the intraovarian role of VEGFR-2 activity on follicular development by choosing a model in which active feedback is absent, the prepuberally hypophysectomized mouse. Hypophysectomy prevents advanced follicle growth and maturation; however, follicle development to the preovulatory stage can be stimulated by administration of gonadotropins. We report that exogenously administered gonadotropins are unable to drive follicle development to the preovulatory stage in the presence of antiangiogenic agent, VEGFR-2–neutralizing Ab’s. This inhibition of follicular development is caused by arrests to both angiogenesis and antrum formation. We conclude that the intraovarian VEGF/VEGFR-2 pathway is critical for gonadotropin-dependent angiogenesis and follicular development.

Vascular endothelial growth factor receptor 2-mediated angiogenesis is essential for gonadotropin-dependent follicle development.

Gonadotropins induce ovarian follicle growth that is coincident with increased follicular vasculature, suggesting a role of angiogenesis in follicle development. Functional studies performed in nonhuman primates show that administration of substances that inactivate VEGF block the development and function of preovulatory follicles as demonstrated by histological analysis or hormone measurements. Blockage of function of VEGF receptor 2 (VEGFR-2) alters follicular hormone secretion, suggesting that the intraovarian effect of VEGF might be mediated by this receptor. The specific mechanism by which follicular development was blocked in these previous studies remains unclear, however. Here we characterize the intraovarian role of VEGFR-2 activity on follicular development by choosing a model in which active feedback is absent, the prepuberally hypophysectomized mouse. Hypophysectomy prevents advanced follicle growth and maturation; however, follicle development to the preovulatory stage can be stimulated by administration of gonadotropins. We report that exogenously administered gonadotropins are unable to drive follicle development to the preovulatory stage in the presence of antiangiogenic agent, VEGFR-2-neutralizing Ab's. This inhibition of follicular development is caused by arrests to both angiogenesis and antrum formation. We conclude that the intraovarian VEGF/VEGFR-2 pathway is critical for gonadotropin-dependent angiogenesis and follicular development.

A randomized cross-over study comparing pharmacodynamic and metabolic variables of a new combiphasic and a well-established triphasic oral contraceptive

In an open-label, randomized, cross-over study in 20 subjects, the short-term effects were investigated of Gracial® (DSG/EE 7 × 25/40 μg/day + 15 × 125/30 μg/day) and Trigynon® (LNG/EE 6 × 50/30 μg/day + 5 × 75/40 μg/day + 10 × 125/30 μg/day) on plasma concentrations of 17β-estradiol and progesterone as well as on carrier proteins (SHBG, CBG, ceruloplasmin), AT-III, carbohydrate metabolism (insulin, glucose, glycosylated proteins) and lipid metabolism (total cholesterol, triglycerides, phospholipids, HDL-C, LDL-C, HDL,-C, HDL3-C, HDL2-C/HDL3-C ratio, Apo A1, Apo B, Apo A1/Apo B ratio).Both preparations adequately and similarly inhibited ovulation in all subjects. Serum levels of carrier proteins were significantly higher with DSG/EE than with LNG/EE, whereas no between-group differences were observed with respect to fasting glucose and insulin, glycosylated proteins (mainly glycosylated albumin) and AT-III activity. DSG/EE showed significantly higher plasma levels than LNG/EE of estrogen-dependent lipid parameters such as triglycerides, HDL-C, HDL2-C, Apo A1, HDL2-C/HDL3-C ratio and Apo A1/Apo B ratio, whereas the levels of LDL-C and Apo B were significantly lower. Both oral contraceptive preparations were equally effective in suppression of follicular development, but combiphasic DSG/EE induced higher plasma levels of carrier proteins and higher plasma levels of potentially anti-atherogenic lipid parameters than did triphasic LNG/EE.

LHRH analogues for contraception in women

LHRH agonists have been comprehensively studied for their ability to disrupt the reproductive cycle in women and are being used in the treatment of hormone-dependent gynaecological disorders. Selected approaches have been evaluated in clinical trials for possible application to contraception. The LHRH antagonists await full clinical evaluation but preliminary clinical studies together with observations from non-human primate investigations allow their potential to be assessed. Despite the different mechanism of action of LHRH analogues and steroids for contraception, many of the issues of acceptability are common to both. The pattern of bleeding, the risk/benefit ratios in relation to cancers of the secondary organs, effects on the cardiovascular system and bone metabolism are major isssues which must be considered with any form of hormonal contraception. LHRH agonists LHRH agonists have been investigated for contraceptive application in a remarkable number of different regimens based on their ability to desensitise the pituitary gonadotroph with subsquent interference with follicular maturation, luteal function or early pregnancy. Approaches based upon intermittent administration at specific stages of the cycle remained as phase I trials (1,2 for reviews) as they seemed to be impractical. The continuous administration of LHRH agonist has been extensively evaluated using either buserelin (200-600 @day) or nafarelin (125-1000 &day) administered by nasal spray for periods of 6-24 months. Dose response studies demonstrated that a problem lay in the variation in estrogen production between individuals. A marked suppression of estrogen produced hot flushes and amenorrhea. Loss of bone mineral would also be predicted. Less suppression of follicular development caused fluctuating blood estrogen concentrations which stimulated the endometrium. Although subsequent bleeding is generally at monthly intervals and of light intensity there are concerns about long-term consequences of exposure of the endometrium to unopposed estrogen. To overcome this problem the agonist has been combined with a progestational agent in a cyclic regimen (3) but application has been limited. LHRH agonists for post-partum contraception During lactation there is a need for a reliable, acceptable and easily administered method of contraception which has no biological effect upon the infant and does not interfere with milk production. An adequate inter-birth interval is of major importance because it enables the mother to recover her physical status and emotional well-being between pregnancies, and confers advantages of improved health and development upon the child. These factors are of particular importance in developing countries. Although the process of lactation has a suppressive effect

Inhibition of Follicular Development by a Potent Antagonistic Analog of Gonadotropin-Releasing Hormone (Detirelix)*

The ability of a potent long-acting antagonistic analog of GnRH to suppress gonadotropin secretion, disrupt follicular development, and inhibit ovulation was studied in six women with normal menstrual cycles. The GnRH antagonist detirelix ([N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10++ +] GnRH; Syntex Research) was administered to six women by sc injection on alternate days during a 27-day period. Six additional women underwent blood sampling only, without receiving detirelix. Within 8 h after the initial injection of detirelix, mean (+/- SEM) serum LH and FSH concentrations decreased by 74 +/- 2% and 26 +/- 3%, respectively. Mean immunoreactive FSH levels, however, returned to baseline after the first 72 h despite continued administration of detirelix. Mean estradiol (E2) concentrations decreased from 165 +/- 15 to 70 +/- 11 pmol/L in the first 24 h. During the treatment period follicular development was inhibited, and none of the six volunteers showed evidence of ovulation, as assessed by serum progesterone (P) levels. Maximal suppression of serum LH and E2 was observed approximately 24 h after each injection of detirelix. Compared to the control volunteers, those receiving detirelix had significantly lower mean serum LH (P less than 0.001), E2 (P less than 0.001), and P (P less than 0.001) levels during treatment; mean FSH concentrations, however, were not statistically different in the treatment and control groups. Rapid recovery of pituitary-ovarian function occurred after completion of treatment. In all six volunteers receiving detirelix, a LH surge occurred 10-16 days after the final injection, followed by increased P levels (greater than 32 nmol/L), indicating ovulation and a luteal phase of normal duration (12-14 days). Detirelix injections elicited local skin reactions (erythema and pruritus), but no systemic side-effects were observed. Thus, this long-acting GnRH antagonist can rapidly suppress gonadotropin secretion, inhibit follicular development, and prevent ovulation.

Relationship between body fatness, ovarian structure and reproduction in mature females from lines of genetically lean or fat broilers given different food allowances

Abstract 1. Reproductive and other characteristics were measured at 34 and 60 weeks of age in broiler breeder hens on 6 different feeding regimes. The hens came from genetically lean and fat lines selected on the basis of low or high 7‐week plasma very low density lipoprotein (VLDL) concentration. 2. Plasma VLDL concentrations were consistently higher at all ages in fat line hens but were not affected by dietary treatment. 3. Mature body weight did not differ between the lines in birds fed ad libitum but with food restriction throughout life, fat line birds were lighter at 34 weeks. 4. There was little difference between the lines in abdominal fatness of birds fed ad libitum up to 60 weeks. Fat line birds were always fatter than lean line counterparts under food restriction. 5. Egg production was higher in lean line birds fed ad libitum but food restriction improved egg production in both lines. Peak egg productions were similar in both lines but there was evidence that the optimal food allowances for egg production was higher in the lean compared with the fat line. 6. Ovarian yellow follicle numbers were highest at 34 weeks in ad libitum fed lean line birds and declined linearly with decreasing body weight caused by food restriction but there was no such relationship in fat line birds. 7. White follicle numbers were higher and follicular atresia was lower in the lean line. 8. It is concluded that poor reproduction in fat line birds was associated with inhibition of follicular development and atresia rather than by high plasma VLDL concentrations promoting excessive yolk formation.

Ovarian follicular response of mares to an equine pituitary extract after suppression of follicular development

Follicular population dynamics were monitored in 36 mares by diagnostic ultrasonography. The objective was to identify the day of physiological selection of the ovulatory follicle in mares in which follicular development was first suppressed with an estrogen-progesterone regimen. The hypothesis was tested that the selection process involves selection for an ovulatory follicle and concurrent selection against the other follicles in the cohort from which the ovulatory follicle arose. The experimental design was based on the consideration that mares treated with equine pituitary extract (EPE) before the time of physiological selection would exhibit a superstimulatory response whereas mares given EPE after the time of selection would not. One group of mares was untreated ( n = 12) and four groups ( n = 6) were given EPE when the diameter of the largest follicle attained 15 mm, 20 mm, 25 mm, and 30 mm after suppression of follicular development with estradiol-17β and progesterone. The mares were examined until ovulation or the diameter of the largest follicle attained 35 mm. Diameters of the largest and second largest follicles and number of follicles in 6 to 10 mm, 11 to 15 mm, 16 to 20 mm, 21 to 25 mm, 26 to 30 mm, and > 30 mm diameter categories were determined. There was a main effect of day ( P < 0.0001) for diameters of the two largest follicles. The group effect and the group by day interaction were significant for diameter of the second largest follicle; the interaction appeared due primarily to increased diameter during the later portion of the experimental period in the 15-mm, 20-mm, and 25-mm groups. Mean diameter of the second largest follicle on the day that the largest follicle reached 35 mm was greater ( P < 0.05) for the 15-mm (32.5 ± 0.9 mm), 20-mm (33.2 ± 1.1 mm), and 25-mm groups (30.8 ± 1.8 mm) than for the untreated (20.1 ± 1.5 mm) and 30-mm groups (22.5 ± 2.4 mm). There was a main effect of group ( P < 0.08 to P < 0.01) and day ( P < 0.006 to P < 0.0001) for all diameter categories. There were more follicles > 30 mm ( P < 0.05) on the day that the largest follicle reached 35 mm in the 15-mm (2.5 ± 0.6) and 20-mm (2.2 ± 0.6) groups than for the untreated (0.8 ± 0.2) and > 30-mm groups (0.8 ± 0.3). The 25-mm group was intermediate (1.2 ± 0.4). In the 15-mm and 20-mm groups versus the 30-mm group there were more ( P < 0.02) follicles 21 to 25 mm and 26 to 30 mm several days before ovulation or the day that the diameter of the largest follicle reached 35 mm. Administration of EPE when the diameter of the largest follicle attained 15 mm, 20 mm, or 25 mm resulted in a superstimulatory response, indicating that selection for an ovulatory follicle and against other follicles had not yet occurred. By the time that the largest follicle reached 30 mm, the ovulatory follicle had already been selected as indicated by the lack of a superstimulatory response. Results indicated that selection of the ovulatory follicle occurred when the diameter of the largest follicle reached between 25 mm and 30 mm and supported the hypothesis that at approximately the time of physiological selection of the ovulatory follicle other follicles in the cohort are committed to atresia.