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Neuroendocrinology of melatonin in reproduction: recent developments.

The circadian melatonin rhythm with high levels in the dark period is important for the synchronization of reproductive response to appropriate environmental conditions in animals. The target sites of melatonin action on reproductive functions remain to be clarified. Using autoradiography (ARG) and radioreceptor binding assays with 2[125I]iodomelatonin, a melatonin agonist, as the radioligand, studies on the sites of melatonin action have increased significantly in the last ten years. The recent cloning of melatonin receptor subtypes also allowed the characterization of receptor(s) to the molecular level. Earlier reports have documented that the hypothalamic-pituitary axis plays a vital role in the regulation of reproduction by melatonin. This is supported in part by the demonstration of melatonin receptors in the suprachiasmatic nuclei (SCN) in the brain and pars tuberalis (PT) in the pituitary. However, the nature of SCN and PT involvement in the reproductive action of melatonin remains unknown. In addition to the hypothalamus and pituitary, the two classical sites of melatonin action, other targets have been identified. The recent demonstration of 2[125I]iodomelatonin binding sites or melatonin receptors in the testis, epididymis, vas deferens, prostate, ovary and mammary gland suggest the concept of multiple sites of melatonin action on the reproductive system. The presence of melatonin receptors in the said tissues is consistent with earlier reports of direct melatonin actions on different levels of the reproductive system. This multiple levels of melatonin action, from the hypothalamus, pituitary, gonads to other reproductive tissues form a robust system of photoperiodic control in animal reproduction. This would guarantee successful gestation and delivery of the offspring at a time with optimum food availability and ultimately favourable for the survival of species. Molecular and cellular studies of melatonin signaling system(s), its regulation and effects on downstream functional events in the future may provide new insights and directions for the study of the physiology and pharmacology of fertility and contraception in animals and humans.

Animals↗

The influence of ovarian activity and uterine involution determined by ultrasonography on subsequent reproductive performance of dairy cows.

The objective of this study was to test the hypothesis that a follicle >8 mm diameter in the ovary ipsilateral to the previously gravid uterine horn (PGUH), between 14 and 28 days postpartum, improves subsequent reproductive performance. Lactating Holstein-Friesian cows (n=284) in 3 commercial herds were examined using transrectal ultrasonography once between 14 and 28 days postpartum to determine associations between uterine and ovarian measurements and subsequent fertility. There were fewer cows with a corpus luteum in the ovary ipsilateral to the PGUH compared with the contralateral ovary (16.9% vs. 37.0%; P<0.001). In addition, in the ovary ipsilateral to the PGUH there were fewer follicles >5 mm diameter (mean +/- SEM; 0.69 +/- 0.06 vs. 1.02 +/- 0.06; P<0.001) and fewer animals with a follicle >8 mm diameter (26.1% vs. 49.6%; P<0.001). These differences between the ovaries ipsilateral or contralateral to the PGUH declined with increasing time between 14 and 28 days postpartum. The presence of a purulent vaginal discharge decreased the number of animals with a corpus luteum in the ovary contralateral to the PGUH (45/143 vs. 60/141; P<0.05), but not in the ovary ipsilateral to the PGUH. The presence of a follicle >8 mm diameter in the ovary ipsilateral to the PGUH was associated with a shorter calving to conception interval compared with animals without such a follicle (99.0 +/- 5.6 days, n=74, vs. 112.8 +/- 4.4 days, n=210; P<0.05). These observations raise an intriguing issue: how does this follicle affect subsequent fertility--does the follicle exert a local influence on the uterus, or vice versa?

Animals↗

Variation in levels of serum inhibin B, testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding globulin in monthly samples from healthy men during a 17-month period: possible effects of seasons.

To obtain information on the scale of the intraindividual variation in testicular hormone, blood samples for inhibin B determination were collected monthly in 27 healthy male volunteers during a 17-month period. In addition, the traditional reproductive hormones FSH, LH, testosterone, estradiol, and SHBG were measured. The intraindividual variation in inhibin B over the study period was, on the average, 10%, corresponding to the assay variation of the inhibin B assay, indicating that most of the observed day to day variation in inhibin B levels in men could be explained by assay variation. A seasonal variation was observed in LH and testosterone levels, but not in the levels of the other hormones. The seasonal variation in testosterone levels could be explained by the variation in LH levels. The seasonal variation in LH levels seemed to be related to the mean air temperature during the month before blood sampling, but not to the length of daylight or the hours of sunshine. In conclusion, our data showed that day to day levels of inhibin B are relatively constant in men and do not seem to be influenced by seasonal factors. In contrast, we found a seasonal variation in LH and testosterone levels in men. The peak levels of both LH and testosterone were observed during June-July, with minimum levels present during winter-early spring. Air temperature, rather than light exposure, seems to be a possible climatic variable explaining the seasonal variation in LH levels.

Adult↗

Computer modeling of human fertility: the impact of reproductive heterogeneity on measures of fertility.

As a result of the paucity of biological markers for both reproductive events and exposure to reproductive toxicants, it is likely that individual members of populations will be misclassified with respect to reproductive performance and xenobiotic exposure. A four-parameter computerized model of fertility (frequency of intercourse, male fecundity, female fecundity, and spontaneous abortion) was developed to explore the effect of misclassification of populations on several measures of fertility. The measures of fertility explored include cumulative percent pregnant, time to pregnancy, cycle specific fertility, and fecundability ratio. The cumulative percent pregnant and time to pregnancy appeared to be insensitive to small changes in reproductive competence. The fecundability ratio decreased in proportion to the size of population exposed to a reproductive toxicant. The three reproductive parameters, time to pregnancy, cumulative percent pregnant, and fecundability, do not appear useful as measures of reproductive heterogeneity in populations. The reproductive heterogeneity of a population was best defined by the change in cycle-specific fertility rate over the period of observation. These simulations suggest that the change in the cycle-specific fertility rate should be evaluated and comparable in all population groups over the period of observation to assure reproductive homogeneity.

Abortion, Spontaneous↗

Effects of deslorelin or hCG administration on reproductive performance in first postpartum estrus mares.

A tendency for deslorelin implants to suppress subsequent follicular growth and delay return to estrus following induced ovulation has been documented in nonlactating mares. To investigate this phenomenon in lactating mares, 22 broodmares in southeast Texas were administered either deslorelin or hCG to induce ovulation in the first postpartum estrus during February and March 2001. Mares were teased daily and examined twice weekly (Tuesdays and Thursdays) by transrectal ultrasonography. When a follicle >35 mm diameter was detected on Tuesday, mares were treated with either 2,500 U hCG administered intravenously or with one implant (2.1 mg) deslorelin administered subcutaneously. Mares were bred every other day until ovulation was detected or until they ceased behavioral estrus, and were examined 16 days after treatment to detect pregnancy. Follicular measurements were recorded for all mares during each examination, and interestrous intervals were recorded for mares not becoming pregnant. Treatment of mares with either hCG or deslorelin resulted in similar ovulatory responses and pregnancy rates. Deslorelin-treated mares had fewer ovarian follicles >20 mm in diameter 16 days after treatment than hCG-treated mares (P < 0.01). Interestrous intervals for mares failing to become pregnant on foal heat breeding were prolonged in deslorelin-treated compared to hCG-treated mares (P < 0.01). Date of treatment was negatively correlated with length of the interestrous interval in deslorelin-treated mares (P < 0.01), but was not correlated with length of interestrous interval in hCG-treated mares (P > 0.10). All mares failing to become pregnant from foal heat breedings became pregnant from later breedings, but the parturition to conception interval was prolonged in deslorelin-treated compared to hCG-treated mares that did not become pregnant on foal heat (P < 0.01).

Animals↗

Production from first-calf beef heifers fed a maintenance or low level of prepartum nutrition and ruminally undegradable or degradable protein postpartum.

Two experiments were conducted in consecutive years to determine the effects of prepartum nutrient level and postpartum ruminally undegraded protein intake on nutrient status, milk production, subsequent calf production, and reproductive performance of 126 crossbred, primiparous beef heifers. Prepartum treatments were low nutrient intake (LN) (approximately 2.5 kg of TDN, .5 kg of CP animal-1.d-1 and maintenance nutrient intake (MN) (5 kg of TDN, 1 kg of CP animal-1.d-1), which were fed for 75 d before parturition. Two postpartum protein supplements were formulated to provide 250 g/d of ruminally degradable protein (RD) and one to supply ruminally undegraded protein (UD) at 250 g/d of additional UD CP compared to the RD supplement. Cholesterol was lower (P less than .01) in heifers given UD than in heifers given RD. Blood urea nitrogen was higher (P less than .01) for UD-fed heifers than for RD-fed heifers and was higher in LN heifers (P less than .06) than in MN heifers. Milk production did not differ (P greater than .11) as a result of LN, MN, UD, or RD. Postpartum cow weight gain was greatest (P less than .01) for UD and LN heifers. The percentage of heifers bred during the first estrous cycle of the breeding season was greater (P less than .02) for UD than for RD. Overall, prepartum nutrition did not interact with postpartum protein supplement, nor did it have any effect on postpartum interval, whereas UD increased cow weight gain postpartum and reduced postpartum interval.

Animal Nutritional Physiological Phenomena↗

Influence of son preference on the contraceptive use and fertility of Sri Lankan women.

The effect of moderate son preference on family size is analysed using data from the 1982 Sri Lanka Contraceptive Prevalence Survey whose respondents were followed-up in the 1985 Sri Lanka Contraceptive Survey. Reported reproductive intentions on desire for additional children were not always reflected in overall contraceptive use. Complicating factors were the use of modern and traditional methods and the role of induced abortion. Longitudinal observations of the 1982-85 period relating women's individual reproductive behaviour to their intentions show no consistent behavioural difference between those with and without sons. However, at any given parity, the proportion reporting at least one additional child born during the intersurvey period was higher among those women who intended to have at least one additional child than among those who wanted to stop childbearing. This analysis suggests that son preference finds expression more through reproductive intentions than through actual fertility behaviour in the follow-up period.

Adolescent↗

Reproductive responses of male Microtus montanus to photoperiod, melatonin, and 6-MBOA.

Juvenile male Microtus montanus were examined for the effects of photoperiod, melatonin, and the naturally occurring reproductive stimulant 6-MBOA on growth and sexual maturation. 6-MBOA, present in sprouting grass, is an important environmental cue used for the initiation of reproduction in natural populations of this species. Long photoperiod (16:8) was stimulatory to body, testes, and seminal vesicle growth, while short photoperiod (8:16) inhibited these parameters. The pineal hormone melatonin, administered via daily afternoon injections (5 micrograms), was also inhibitory to all of the above parameters as well as to serum testosterone. 6-MBOA, administered via injection (0.0001-100 micrograms) or dietary means (0.1 or 1.0 microgram/gm unsifted chow), appeared unable to augment the rate of maturation in long-photoperiod-stimulated animals. When short-photoperiod animals were treated with high doses of the compound (100 micrograms injected or 1.0 micrograms/gm sifted chow), body and gonadal growth was inhibited to a greater extent than when animals were exposed to short photoperiod alone, and serum LH was reduced. Lower doses of the compound had no effect. Melatonin-treated animals experienced less maturational inhibition when simultaneously given a low dose of 6-MBOA-coated chow (1.0 micrograms/gm unsifted chow). A higher dose of 6-MBOA (1.0 micrograms/gm sifted chow) was ineffective in preventing the response to melatonin. These results indicate that 1) male M. montanus utilize photoperiod, rather than 6-MBOA, as a primary environmental cue, 2) high doses of 6-MBOA can be inhibitory under short photoperiod, 3) juvenile male voles are highly sensitive to the inhibitory effects of exogenously administered melatonin, and 4) 6-MBOA can partially prevent the inhibitory effects of melatonin on growth and sexual maturation.

Analysis of Variance↗

Postpartum reproductive function: association with energy, metabolic and endocrine status in high yielding dairy cows.

This study evaluated the effect of metabolic, endocrine and energy status on onset of ovarian cycle, days open (DO), and conception at first service in 90 multiparous Holstein cows, housed at a research farm. Dry matter intake, milk yield and body weight were measured daily from Week 2 antepartum (a.p.) to Week 20 postpartum (p.p.). Milk composition was determined four times per week and milk acetone was measured weekly. Blood samples for the determination of glucose, non-esterified fatty acids, cholesterol, creatinine, albumin, urea, beta-hydroxybutyrate, leptin, insulin, insulin-like growth factor-1, growth hormone, 3,5,3'-triiodothyronine (T(3)), and thyroxine (T(4)) were taken 2 weeks a.p., in Weeks 1-16, and 20 p.p. between 7:30 and 9:00 h. The onset of ovarian cycle was specified by weekly gynecological examination and by skim milk progesterone determination by radioimmunoassay (twice per week). Energy balance (EB) traits were calculated and expressed as accumulated negative EB from calving to EB equilibrium, EB nadir (EBN), rate of EB recovery after EBN (EBR), and time from calving to EBN and to EB equilibrium, respectively. The onset of ovarian cycle p.p. was not related to EB. However, a low degree of EBN and a fast EBR were associated with fewer DO, and EB at first service was positively related to conception. High plasma levels of T(3) and T(4) p.p. were associated with an early start of ovarian cycle, and high concentrations of glucose and cholesterol with a short calving to conception interval. Conception at first service was positively related to EB at first service and progesterone concentration 10-13 days after first service. In conclusion, thyroid hormones may play an important role in resumption of ovarian cyclicity p.p., and a good energy status enhances the chance of conception at first service and shortens DO.

Animals↗

Body condition and suckling as factors influencing the duration of postpartum anestrus in cattle: a review.

Prolonged postpartum anestrus is a main factor limiting reproductive efficiency in cattle, particularly in Bos indicus and Bos taurus/Bos indicus cows from tropical regions, because it prevents achievement of a 12 month calving interval. During anestrus, ovulation does not occur despite ovarian follicular development, because growing follicles do not mature. Although many factors affect postpartum anestrus, nutrition and suckling are the major factors influencing the resumption of postpartum ovarian cycles, as they affect hypothalamic, pituitary and ovarian activity and thus inhibit follicular development. Under-nutrition contributes to prolonged postpartum anestrus, particularly among cows dependent upon forages to meet their feed requirements and it apparently interacts with genetic, environmental or management factors to influence the duration of anestrus. The nutritional status or balance of an animal is evaluated through body condition score (BCS), as it reflects the body energy reserves available for metabolism, growth, lactation and activity. There is a converse relationship between energy balance and time to resumption of postpartum ovarian activity; inadequate nutrient intake results in loss of weight and BCS and finally cessation of estrous cycles. Suckling interferes with hypothalamic release of GnRH, provoking a marked suppression in pulsatile LH release, resulting in extended postpartum anestrus. The effects of suckling on regulation of tonic LH release are determined by the ability of the cow to identify a calf as her own or as unrelated. Vision and olfaction play critical roles in the development of the maternal-offspring bond, allowing the cow to identify her own calf, and abolition of both senses attenuates the negative effects of suckling on LH secretion. Thus, the maternal-offspring bond is essential for prolonged postpartum suckling-induced anovulation, and the suppressive influence of suckling is independent of neurosensory pathways within the teat or udder.

Anestrus↗

[The reproductive function following a hydatidiform mole].

This paper starts with a short description of the history of the discovery of the hydatidiform mole ( Tulp in 1641) and of the treatment (before 1956, hysterectomy in most cases). After 1961 chemotherapy started to be used even in patients who had cerebral metastases. 72 patients who had attended Professor Hubinont 's department in the University Hospital of Saint-Pierre in Brussels between January 1971 and December 1981 were followed up. Questionnaires were sent to the patients and to their doctors who were treating them in order to try and find out what had happened in subsequent pregnancies and what the maternal and fetal consequences and complications were. The social class and the marital status of the patients was also considered as well as their wish to become pregnant again. Of the 72 cases that were followed up after evacuation 63 (87.5%) recovered while 9(12.5%) had clinical, biological or radiological signs of persistent non-metastatic (3) and metastatic (6 cases) active disease. The department asked patients not to become pregnant in the year following evacuation of the mole. 10% were sterilised, 4 by hysterectomy and 4 by tubal ligation. 42% used the oral contraceptive pill and 34% (24 cases) condoms. Control follow-up of patients who became pregnant was compared with a group of 2 529 pregnancies in Saint-Pierre Hospital during the year 1981. 44 out of the 72 patients who were followed up after hydatidiform mole became pregnant with a total of 52 pregnancies. Ten became pregnant in the first 6 months after attempting it, 11 between 6 and 12 months and 23 after a delay of 12 months. Out of the 52 pregnancies, 34 5%) had a live baby at term. 6 were premature and 31 out of 34 babies delivered at term were delivered vaginally and 3 by Caesarean. There were 9 spontaneous abortions (17%) and 2 terminations of pregnancy (4%). Three patients had repeated non-intentional abortions and one had a still-birth for which the cause could not be found. Only one other had a second mole. When these results are compared with the histories of these patients before they had the hydatidiform mole there did not seem to be any increase in the number of spontaneous abortions or premature labours, nor was there when this group was compared with a control group. Only one of the 38 live-born children showed a major congenital abnormality which was varus equinus. There was no possibility of picking out statistically anything of value as far as congenital malformations was concerned.

Adolescent↗

Lactational control of reproduction.

In most mammalian species lactation suppresses fertility. There is no doubt that it is the suckling stimulus that provides the controlling signal, and, in human reproduction, this is the only truly physiological signal that suppresses fertility in normally nourished, healthy women. In breastfeeding women, the return of normal fertility follows a relatively well-defined path progressing through: an almost complete inhibition of gonadotrophin-releasing hormone/luteinizing hormone (GnRH/LH) pulsatile secretion in the early stages of lactation; return of erratic pulsatile secretion with some ovarian follicle development associated with increases in inhibin B and oestradiol; a resumption of apparently normal follicle growth associated with a normal increase in oestradiol, but often an absence of ovulation, or formation of an inadequate corpus luteum; and a return to normal ovulatory menstrual cycles. A key element in controlling the rate of this progression is the impact of the suckling stimulus on the GnRH pulse generator, a common feature of lactation in those species for which there is information. The variability in the duration of lactational amenorrhoea between women is related to the variation in the strength of the suckling stimulus, a unique situation between each mother and baby. Full breastfeeding can provide a reliable contraceptive effect in the first 6 to 9 months, but the precise mechanisms whereby the suckling stimulus affects GnRH pulsatile secretion remain unknown. Many studies on the hypothalamic pathways that might be involved in the translation of the neural suckling stimulus to suppression of hypothalamic GnRH secretion have been undertaken, principally in rats. In women, suckling increases the sensitivity of the hypothalamus to the negative feedback effect of oestradiol on suppressing the GnRH/LH pulse generator, a mechanism that appears to be common across species. In contrast, the role of prolactin in the control of GnRH appears to be species-dependent, with the importance varying from none to an important role in late or throughout lactation. In women, there is little evidence for a role of leptin, opioids or dopamine, although this may merely reflect the ethical dilemma of being able to give sufficient drug to test the system in the mother since these drugs will pass through the breast milk to the baby. Regardless of mechanism, practical guidelines for using breastfeeding as a natural contraceptive have been developed, which allows mothers to utilize the only natural suppressor of fertility in women as an effective means of spacing births.

Amenorrhea↗

Influence of body condition and bovine somatotropin on estrous behavior, reproductive performance, and concentrations of serum somatotropin and plasma fatty acids in postpartum Brahman-influenced cows.

Ninety-nine multiparous Brahman-influenced (1/4 to 3/8 Brahman) cows were managed to achieve low (BCS = 4.3 +/- 0.1; n = 50) or moderate (BCS = 6.1 +/- 0.1; n = 49) body condition (BC) to determine the influence of bovine somatotropin (bST) on estrous characteristics, reproductive performance, and concentrations of serum GH and plasma NEFA. Beginning 32 d postpartum, cows within each BC were assigned randomly to treatment with or without bST. Non-bST-treated cows received no treatment, and treated cows were administered bST (Posilac, 500 mg s.c.) on d -35, -21, and -7 before initiation of the breeding season. On d -7, all cows received an intravaginal, controlled internal drug-releasing (CIDR) device. On d 0 (initiation of the 70-d breeding season), the CIDR were removed and cows received prostaglandin F2alpha (PGF2alpha). Blood samples were collected from the median caudal vein of the cows at each bST treatment and at d -28 and 0. Estrous behavior was monitored by radiotelemetry during the first 30 d of the breeding season. Growth hormone was increased (P < 0.05) in low and moderate BC cows treated with bST. The percentage of cows detected in estrus during the first 30 d of the breeding season was decreased (P = 0.05) for low BC (64%) compared with moderate BC (82%) cows. The interval to first estrus tended (P = 0.07) to be shorter in low BC-bST-treated cows (3.7 +/- 1.9 d) than in moderate BC-bST-treated cows (9.6 +/- 1.8 d). During the first 30 d of the breeding season, cows in low BC had a decreased (P = 0.02) number of mounts received and increased (P = 0.001) quiescence between mounts compared with cows in moderate BC. The number of mounts received was reduced (P = 0.04) in bST-treated cows. More (P = 0.02) cows treated with bST became pregnant during the first 3 d of the breeding season compared with non-bST-treated cows. The cumulative first-service conception rate tended (P = 0.07) to be greater for bST-low BC cows than non-bST-treated cows in low or moderate BC. On d 0, NEFA were greater (P < 0.05) in bST-treated vs. non-bST-treated cows. Low BC and bST reduced the intensity of behavioral estrus in postpartum Brahman-influenced cows. However, bST increased the first-service conception rate during the first 30 d of breeding and pregnancy rates during the first 3 d of breeding in postpartum Brahman-influenced cows.

Animal Husbandry↗

Effect of photoperiod on reproductive activity and hair in mares.

The effects of photoperiod on reproductive activity and hair changes in pony mares were studied in 2 experiments. In experiment I, the effect of a fixed daily photoperiod on the onset of the breeding season was studied in 36 mares from Nov 13, 1973, to June 13, 1974. The 4 treatment groups were as follows: daily photoperiod equivalent to the normal day length (control group); constant light 24 hours a day with no dark (L24:D0 group); 16-hour daily photoperiod with 8 hours of dark (L16:D8 group); and 9-hour daily photoperiod with 15 hours of dark (L9:D15 group). The intervals from beginning of experiment to 1st ovulation of breeding season, to shedding of hair in tufts, and to appearance of a smooth coat were shorter (P less than 0.05) for L16:D8 group (107.1 +/- 11.1, 56.0 +/- 0, and 145.8 +/- 4.0 days, respectively) than for control, L24:D0, and L9:D15 groups and were shorter (P less than 0.05) for L24:D0 group (less than 156.1 +/- 12.2, 99.5 +/- 9.5, and 173.9 +/- 9.9 days, respectively) than for control group (192.1 +/- 3.3, 134.9 +/- 8.9, and 205.0 +/- 0 days, respectively) or L9:D15 group (less than 200.3 +/- 5,8, 150.6 +/- 12.9, and 201.7 +/- 3.3 days, respectively). These intervals were not significantly different between the control group and the L9:D15 group, but fewer (P less than 0.05) mares in the L9:D15 group had at least 1 ovulation by termination of the project. In experiment II, the effect of photoperiod on onset of anestrus was studied in 3 groups of 7 mares each. Mares in group A, as part of a previous experiment, were induced to enter the breeding season earlier than normal by a gradual increase in daily photoperiod beginning on Oct 13, 1972. From Feb 16, 1973, to June 22, 1973, group A mares were maintained at a fixed daily photoperiod of 15 hours 23 minutes. Mares in group B, as part of a previous experiment, were kept under environmental conditions simulating normal conditions in southern Wisconsin. On June 22, 1973 (beginning of the present experiment), the following treatments began: groups A and B were exposed to natural day length. In addition, 7 mares (group C) were allotted from a band of mares that had been exposed to natural day length and were exposed to 15-hour 23-minute daily photoperiod from the beginning of the present experiment (June 22, 1973) to the end (June 22, 1974). The interval to onset of anestrus was longer (P less than 0.05) for group C mares (234.6 +/- 35 days) than for group B mares (133.6 +/- 16.5 days). Significant difference did not exist between group A (144.0 +/- 45.9 days) and group B. A fixed daily photoperiod of 16 or 24 hours induced early onset of the breeding season and early shedding of hair, with development of a smooth coat. A photoperiod of 9 hours retarded the onset of the breeding season. Mares induced to begin the breeding season earlier than normal did not become anestrous earlier than normal. Mares kept on a long daily photoperiod in the fall became anestrous later than normal.

Anestrus↗

Perinatal exposure to genistein alters reproductive development and aggressive behavior in male mice.

Exposure to endocrine disrupting chemicals adversely affects reproductive development and behavior in males. The goal of this study was to determine if exposure to genistein, an isoflavone found in soy, during early periods of sex differentiation alters reproductive development and behavior in male mice. Female C57BL/6 mice were fed a phytoestrogen-free diet supplemented with 0, 5 or 300 mg/kg of genistein throughout gestation and lactation. Anogenital distance (AGD) and body mass of male offspring was measured weekly from postnatal days 2-21, timing of preputial separation was assessed at puberty, and in adulthood, reproductive organ masses, sperm and testosterone production, and reproductive and aggressive behaviors were assessed. Exposure to genistein resulted in smaller AGD are reduced body mass, with the low-dose diet exerting a greater effect. Timing of preputial separation, adult reproductive behavior, sperm concentrations and testosterone production were not influenced by genistein treatment at either dose. Aggressive behaviors were decreased, whereas defensive behaviors were increased, in males that received the low-dose genistein diet. Exposure to genistein during critical periods of sex differentiation results in concurrent and persistent demasculinization in male mice. Phenotypic and behavioral abnormalities induced by genistein showed a non-monotonic response, where treatment with a low dose exerted a greater effect than treatment with a high dose of genistein. Given the popularity of soy infant formulas, the influence isoflavone exposure on reproductive and behavioral health in boys and men should be considered.

Administration, Oral↗

Effect of cadmium on morphology and steroidogenesis of cultured human ovarian granulosa cells.

Cadmium (Cd) is able to decrease preovulatory luteinizing hormone (LH) levels in blood and inhibit ovulation in rats. In this study the direct effects of Cd on steroidogenesis in granulosa cells were investigated. The cells obtained from ovarian follicular aspirates of 41 women undergoing in vitro fertilization (IVF) were cultured. Cadmium-induced alterations in the cellular morphology and in the production of progesterone by the cells was determined after exposure to concentrations of 8, 16, 32 and 64 microM CdCl2 for 2, 4, 8, 24 and 48 h. Progesterone secretion by granulosa cells could be stimulated with increasing concentrations of follicle-stimulating hormone (FSH). Combined effects of Cd and FSH were also studied. Cadmium diminished progesterone production in unstimulated and FSH-supported cells depending on its concentration and the exposure time. Follicle-stimulating hormone (100 ng ml[-1]) protected against Cd-induced suppression of progesterone production. Cadmium interfered with cell-cell junctions and the adherence of cells. No protective effect of FSH on Cd-induced alteration in cell morphology could be observed. Retraction of cytoplasmic extensions occurred at a lower dose and within a shorter exposure than a decrease in progesterone production. In conclusion, Cd exerted a direct effect on both granulosa cell morphology and on steroid biosynthesis. The lowest Cd concentration (16 microM) that was able to reduce progesterone production was about 3.5 times higher than levels reported in the ovary of a female smoker. The presented data can help to define environmental, occupational and life-style (smoking) risk factors in gonadal function during the preconception period of the female reproductive lifespan.

Adult↗

Testosterone and energetics in wild chimpanzees (Pan troglodytes schweinfurthii).

Ovarian function in female hominoids is sensitive to both energy flux and energy balance, resulting in a reduced probability of conception during periods when a successful reproductive outcome is less likely. However, the extent to which energetic factors constrain gonadal function in male hominoids is not clear. We examined the effects of both acute and chronic variation in energy availability on urinary testosterone (T) levels in adult male chimpanzees. Acute changes in energy availability, which were assayed by means of observational data on feeding behavior, did not result in decreased T production for 11 individuals at Kibale National Park, Uganda. Chronic energy shortages, on the other hand, may be associated with lower T levels in this population. Adult males in Kibale (n=11), who maintain suboptimal access to energy, exhibit significantly lower urinary T levels than males in captivity (n=11), who are more sedentary and better fed. These results suggest that data on hormonal function in captive chimpanzees should be interpreted with caution because individuals may produce T at levels well above those that are typical in the wild. They also suggest that short-term variations in T levels in male hominoids are more likely to be explained by social factors than by energetic ones.

Animals↗