Female Reproductive Cycle Research Articles

Intraocular pressure in postmenopausal Nigerian women with and without systemic hypertension

Background: Mean intraocular pressure (IOP) in postmenopausal women has been reported higher than that in menstruating women. Also, intraocular pressure is said to be positively correlated with systemic blood pressure. No previous study in Nigeria has compared intraocular pressure in postmenopausal women with and without systemic hypertension. Purpose: To investigate the effects of menopause on intraocular pressure in subjects with and without high blood pressure. Methods: Normotensive and hypertensive premenopausal and postmenopausal subjects in the same agerange of 45 to 55 years were studied. Intraocular pressure was measured with the hand-held Kowa applanation tonometer. Blood pressure was taken in the sitting position at the right upper arm using a manual mercury sphygmomanometer with the right cuff size. The average of two readings was recorded. Results: Mean IOP for premenopausal normotensive women was 14.58 ± 2.56 mmHg whilethat of postmenopausal normotensive women was16.15 ± 1.80 mmHg (p<0.05). Also, the difference in mean IOP between premenopausal hypertensive (16.58 ± 3.23 mmHg) and postmenopausal hypertensive women (18.24 ± 3.89 mmHg)was statistically significant (p<0.05). A statistically significant and positive correlation was observed between IOP and systemic blood pressure in postmenopausal hypertensive women, p<0.05.Conclusion: Menopause significantly increases intraocular pressure. Mean intraocular pressure of hypertensive postmenopausal women was significantly higher than that of normotensive post-menopausal women, (p<0.05). Knowledge of the normal level of intraocular pressure during various stages of the female reproductive cycle may help during glaucoma screening. (S Afr Optom 2011 70(3) 117-122)

Impact of Sex and Gonadal Hormones on Cocaine and Food Reinforcement Paradigms.

Men and women express sexually dimorphic patterns of cocaine abuse, such that women progress faster from initially trying cocaine to becoming dependent upon the drug and display a greater incidence of relapse. Sex differences in response to cocaine are also seen in the laboratory in both humans and animal models. In this review, animal models of cocaine abuse that have reported sex differences in appetitive reinforcement are discussed. In both human and animal studies, sex differences in the subjective and behavioral effects of cocaine are often related to the female reproductive cycle and ovarian hormones. As a comparison, food reinforcement studies have shown the opposite profile of sex differences and the impact of sex steroids on food intake and response rate. In contrast, limited attention has been given to "choice" models in rodents of either sex, however, our recent studies have indicated a role of sex and estrogen in cocaine choice over food with intact females, and OVX females treated with estrogen, choosing cocaine significantly more than males. Interestingly, estrous cycle phase does not seem to impact cocaine choice as it does response rate in single-reinforcer studies, suggesting that genomic rather than neurosteroid effects of estrogen modulate sex differences in this model. Future studies should more fully explore the impact of sex hormones on concurrent reinforcement and discrete choice models of addiction.

Effect of Photoperiod on Gonadal Steroid Hormone Levels and Reproductive Cycles of Northern Fur Seals (Callorhinus ursinus)

The northern fur seal (Callorhinus ursinus) is a migratory marine mammal belonging to the family Otariidae that breeds on the islands in the North Pacific Ocean, Bering Sea, Sea of Okhotsk, and near the coast of California during summer (Peterson 1968; Gentry 1998). Their reproduction is characterized by extreme polygyny and highly synchronized annual cycles that are concentrated around the boreal summer (Peterson 1968; Trites 1992; Gentry 1998). Females arrive at breeding sites in early July, give birth within 36 hours, and then enter estrus and copulate within a few days (Peterson 1968). Although active gestation persists for approximately eight months, the total duration of gestation period is approximately one year because of the embryonic diapause (delayed implantation), which accurately synchronizes the annual reproductive cycle (Craig 1964; Boyd 1991). Males return to the breeding sites approximately one month before females, establish their territories in the breeding area, and maintain breeding activities for approximately two months (Peterson 1968). Photoperiod is commonly cited as the main trigger for the synchronization of the annual reproductive cycles of pinnipeds (Boyd 1991; Atkinson 1997; Boyd et al. 1999), and this theory is supported by several studies. Temte (1985) compared the mean dates of parturition between the two wild populations of northern fur seals in Alaska (57°N) and California (33°N) and suggested that a mean photoperiod of 12.5 h/day in autumn acts as a trigger for the termination of embryonic diapause and initiation of implantation to synchronize parturition (also see Spotte and Adams 1981). Kiyota et al. (2009) also observed a significant latitudinal variation in the parturition of captive northern fur seals in Japan, which supported the theory of photoperiodic control of the reproductive cycle. The effect of photoperiod on reproductive cycles has been only experimentally demonstrated in harbour seals (Phoca vitulina) (Bigg and Fisher 1975). Bigg and Fisher (1975) demonstrated that estrus occurred earlier than usual during extended photoperiods and was delayed during shortened photoperiods. However, Daniel (1981) did not detect any effect of a shortened photoperiod on the rate of blastocyst development in northern fur seals. Boyd (1991) interpreted the finding of Daniel’s study to be the result of the relatively insignificant shortened photoperiod and/or the short study period. Seasonal changes that occurred in the testicular activity of male fur seals in captivity corresponded with those that occurred in males in the wild (Kohyama et al. 1999; Tsubota et al. 2001). These studies indicate that photoperiodic control of the male reproductive cycle is similar to that of female reproductive cycle, but this photoperiodic effect has not been extensively studied (Boyd 1991). Photoperiod has been reported to control the timing of implantation and parturition in pinnipeds (Temte 1985). However, this interpretation has not been applied to the timing of estrous and ovulation of non-pregnant females or the testicular activities of males. Other mammals, such as Siberian hamsters (Phodopus sungorus) and gray mouse lemurs (Microcebus murinus), are defined as long-day breeders because their reproductive activities increase in response to day length as the seasons change from spring to summer (Goldman 1991, 1999; Perret and Aujard 2001). Therefore, we aimed to determine whether the reproductive cycles of both female and male northern fur seals would be altered under experimentally induced conditions of extended photoperiods. Seasonal changes in gonadal steroid hormone levels and body weight were used as indicators of the reproductive cycle indices, because changes in these factors in relation to the reproductive cycle have previously been described (Kiyota et al. 1999; Kohyama et al. 1999). The effects of photoperiod on seasonal changes in reproductive cycles

Hormonal Monitoring of Reproductive Status in Monogamous Wild Female Owl Monkeys (Aotus azarai) of the Argentinean Chaco

The Neotropical owl monkeys (Aotus spp.) are a good model for evaluating the hypothesis that monogamy may arise if female reproductive cycles limit the mating potential of males. To evaluate this hypothesis, we first needed to assess the feasibility of using fecal sampling for monitoring the reproductive status of females. We collected fecal samples (n = 242, from 7 females) from wild adult Aotus azarai females in the Gran Chaco forests of Argentina during 3 years. Fecal estrone-1-glucuronide (E₁C) and pregnenadiol-3-glucuronide (PdG) tended to rise in parallel during the luteal phase. The average cycle length was 22 ± 3 days (n = 5 females, 10 cycles). We identified 2 conceptive cycles and characterized the E₁C and PdG profiles of 2 pregnancies. This report is the first of its kind on wild female owl monkeys. Despite the difficulties in sample collection and processing in the field and providing a species-specific validation in the laboratory, we show that fecal samples from A. azarai can be used for monitoring female reproductive status and function.

Farnesoic acid and methyl farnesoate production during lobster reproduction: Possible functional correlation with retinoid X receptor expression

Farnesoic acid (FA) and methyl farnesoate (MF) are juvenile hormone-related compounds secreted by the mandibular organ (MO) of crustaceans and play an important role in stimulation of ovarian maturation. To better understand how the MO activity influences female reproduction by secretion of FA and MF, the biosynthesis and release of these two compounds were measured in vitro by the incorporation of l-[ 3H-methyl]methionine into MF and [2- 14C]acetate into FA by the MO of Homarus americanus. The production of FA is 7.5 times that of MF, and most FA and MF synthesized remained within the gland, and was not released into the surrounding medium. Most FA and MF were synthesized in the anterior fan-fold region of the MO. The rates of biosynthesis of FA and MF were stage-related, with maximal production occurring during secondary vitellogenesis (i.e. stages 4 and 5). A potential juvenoid receptor, retinoid X receptor (RXR), HaRXR, was characterized using PCR cloning techniques. HaRXR belongs to the nuclear hormone receptor superfamily and its deduced amino acid sequence shares a high homology to other RXRs of crustaceans, insects, and vertebrates. Transcripts of HaRXR can be detected in many tissues, and significant high expression level was detected in the MO, especially in the anterior fan-fold region. Expression of HaRXR was also related to reproductive stage, and maximal level of expression was observed at stage 4, in which secondary vitellogenesis is occurring. Changes in transcript level of HaRXR and the rates of FA/MF biosynthesis in the female reproductive cycle indicate that HaRXR and FA/MF may play important roles in crustacean reproduction.

Medicalizing the female reproductive cycle in rural Ireland, 1926-56*

This article highlights the parameters of a lifecycles project that was funded by the Irish Research Council for the Humanities and Social Sciences, entitled ‘From the cradle to the grave: lifecycles in modern Ireland (pilot study: maternity)’. The project used individual hospital records to bring the regional effects of ‘medicalization’ outside metropolitan areas into a sharper focus. With an emphasis on rural Ireland from 1926 to 1956, this ‘pilot’ study used longitudinal data modelling to explore the medicalization of the female reproductive cycle in a general hospital and again in a psychiatric hospital setting. The project team chose disparate clinical settings to test how people understood their functions, to see, for example, if medical cases were presenting to the psychiatric setting. This article describes the digitization and data modelling processes and the parameters of the research agenda. It locates the broader medical and statistical findings of the project in their socio-economic context to highlight whether such matters conditioned when and how women resorted to medical care. It discusses the analytical challenges that the project posed and points to avenues of further research and future publications. It concludes that for historical reasons, in the rural Irish context, people engaged more freely with the asylum than the general hospital setting.

A Computational Tool for Quantitative Analysis of Vascular Networks

Angiogenesis is the generation of mature vascular networks from pre-existing vessels. Angiogenesis is crucial during the organism' development, for wound healing and for the female reproductive cycle. Several murine experimental systems are well suited for studying developmental and pathological angiogenesis. They include the embryonic hindbrain, the post-natal retina and allantois explants. In these systems vascular networks are visualised by appropriate staining procedures followed by microscopical analysis. Nevertheless, quantitative assessment of angiogenesis is hampered by the lack of readily available, standardized metrics and software analysis tools. Non-automated protocols are being used widely and they are, in general, time - and labour intensive, prone to human error and do not permit computation of complex spatial metrics. We have developed a light-weight, user friendly software, AngioTool, which allows for quick, hands-off and reproducible quantification of vascular networks in microscopic images. AngioTool computes several morphological and spatial parameters including the area covered by a vascular network, the number of vessels, vessel length, vascular density and lacunarity. In addition, AngioTool calculates the so-called “branching index” (branch points / unit area), providing a measurement of the sprouting activity of a specimen of interest. We have validated AngioTool using images of embryonic murine hindbrains, post-natal retinas and allantois explants. AngioTool is open source and can be downloaded free of charge.

A Modified Hai–Murphy Model of Uterine Smooth Muscle Contraction

We extend and analyze the Wang and Politi modified Hai-Murphy model of smooth muscle cell contractions to capture uterine muscle cell response to variations in intracellular calcium concentrations. This model is used to estimate values of unknown parameters in uterine smooth muscle cell cross-bridging. Uterine motility is responsible for carrying out important processes throughout all phases of the nonpregnant female reproductive cycle, including sperm transport, menstruation, and embryo implantation. The modified Hai-Murphy partial differential equation model accounts for the displacement of myosin cross-bridge heads relative to their binding sites. This model was originally developed for the study of airway contractions; we now extended it for use in modeling nonisometric uterine contractions. Our extended model incorporates cross-bridge position and contractile velocity into the original model, resulting in more accurate modeling of the initial stages of contraction and modeling nonisometric contractions. Numerical simulations show that the contraction rate in our extended model is faster than the original Hai-Murphy model. These simulations provide quantitative estimates for the increased level of responsiveness of our extended model to intracellular calcium concentrations. The extended model and new parameter estimates for the cross-bridging can be coupled with uterine flow models to advance our understanding of embryonic motility and intrauterine flow.

Lipophorin acts as a shuttle of lipids to the milk gland during tsetse fly pregnancy

During pregnancy in the viviparous tsetse fly, lipid mobilization is essential for the production of milk to feed the developing intrauterine larva. Lipophorin (Lp) functions as the major lipid transport protein in insects and closely-related arthropods. In this study, we assessed the role of Lp and the lipophorin receptor (LpR) in the lipid mobilization process during tsetse reproduction. We identified single gene sequences for GmmLp and GmmLpR from the genome of Glossina morsitans morsitans, and measured spatial and temporal expression of gmmlp and gmmlpr during the female reproductive cycle. Our results show that expression of gmmlp is specific to the adult fat body and larvae. In the adult female, gmmlp expression is constitutive. However transcript levels increase in the larva as it matures within the mother’s uterus, reaching peak expression just prior to parturition. GmmLp was detected in the hemolymph of pregnant females and larvae, but not in the uterine fluid or larval gut contents ruling out the possibility of direct transfer of GmmLp from mother to offspring. Transcripts for gmmlpr were detected in the head, ovaries, midgut, milk gland/fat body, ovaries and developing larva. Levels of gmmlpr remain stable throughout the first and second gonotrophic cycles with a slight dip observed during the first gonotrophic cycle. GmmLpR was detected in multiple tissues, including the midgut, fat body, milk gland, spermatheca and head. Knockdown of gmmlp by RNA interference resulted in reduced hemolymph lipid levels, delayed oocyte development and extended larval gestation. Similar suppresion of gmmlpr did not significantly reduce hemolymph lipid levels or oogenesis duration, but did extend the duration of larval development. Thus, GmmLp function as the primary shuttle for lipids originating from the midgut and fat body to the ovaries and milk gland to supply resources for developing oocytes and larval nourishment, respectively. Once in the milk gland however, lipids are apparently transferred into the developing larva not by lipophorin but by another carrier lipoprotein.

Sperm Utilization Patterns and Reproductive Success in Captive Loggerhead Turtles (Caretta caretta)

Abstract We investigated the effects of the order of sequential matings in captive female loggerhead turtles (Caretta caretta) on the paternity of their successive clutches. Paternity analysis revealed that only 3 of the 7 successive clutches were multiply sired, although all egg-laying females were observed to copulate with multiple males prior to egg-laying. In multiply sired, successive clutches of particular females, the relative paternal contributions of different males did not vary, although some potentially successful matings were observed during internesting intervals. Prior to nesting periods, males showed mating in response to the female reproductive cycle in which the cumulative durations of mountings observed by highly sensitive cameras peaked at 21–40 days before any individual female laid her first clutch. A regression line between cumulative duration of mountings and relative parental contributions for 21–40 days before laying the first clutch fit a predictive equation for sperm competition...

Estrogen regulation of the dopamine-activated GIRK channel in pituitary lactotrophs: implications for regulation of prolactin release during the estrous cycle

Prolactin (PRL), synthesized and secreted from lactotrophs of the anterior pituitary gland, is tonically inhibited by hypothalamic dopamine (DA) throughout the female reproductive (estrous) cycle. Our laboratory has shown that DA hyperpolarizes these cells by activating G protein-coupled inwardly rectifying K(+) (GIRK) channels; however, this response is only observed on proestrus. While the cellular mechanisms that allow for functional expression of this unique DA-signaling pathway are unclear, we hypothesized that activation of the DA-GIRK effector pathway is due to the rise in circulating estrogen (E₂) during the preceding day of diestrus. Thus, we examined the effects of E₂ on primary lactotrophs isolated from female rats. Treatment with a physiological concentration of E₂ (40-80 pg/ml, in vivo or in vitro) induced a proestrous phenotype in diestrous lactotrophs. These cells exhibited a DA-induced membrane hyperpolarization, as well as a secretory rebound of PRL following DA withdrawal (characteristic of proestrous cells). Internal dialysis of GTPγS demonstrated that E₂ exposure enabled functional expression of GIRK channels, and this regulation by E₂ did not involve the D₂R. The effect of E₂ was blocked by the receptor antagonist, ICI 182,780, and by the protein synthesis inhibitor, cycloheximide. Single-cell analysis revealed increased mRNA expression of GIRK channel subunits in E₂-treated lactotrophs. While E₂ is known to have multiple actions on the lactotroph, the present findings illuminate a novel action of E₂ in lactotrophs-regulation of the expression of a DA effector, the GIRK channel.

Reproduction in the threatened crayfish Austropotamobius pallipes (Decapoda, Astacidae) in the Licenza brook basin (central Italy)

Austropotamobius pallipes is a vulnerable crayfish, and therefore it is necessary to analyse reproduction in the extant populations. Details of the female annual reproductive cycle in a Mediterranean population are provided for two consecutive years. Maternal-size-related variables and date of collection have been considered in relation to the number of ovarian and pleopodal eggs. Reproductive data from 2587 females collected by hand and traps are reported. In total, 204 (14.69%) and 231 (15.93%) individuals in 2003 and 2004, respectively, were ovigerous. Demonstrable differences exist between ovarian and pleopodal egg counts. In particular, ovarian egg counts were considerably higher than expected pleopodal egg numbers. Mating begins in November and is followed by egg laying in early December–January. Berried females occur until May–June, when hatching occurs. The numbers of both ovarian and pleopodal eggs are correlated with the size of females, although fecundity slightly decreases in larger females. The histology of the reproductive organs of both sexes is also analysed.

Regulation of the female rat estrous cycle by a neural cell-specific epidermal growth factor-like repeat domain containing protein, NELL2.

NELL2, a protein containing epidermal growth factor-like repeat domains, is predominantly expressed in the nervous system. In the mammalian brain, NELL2 expression is mostly neuronal. Previously we found that NELL2 is involved in the onset of female puberty by regulating the release of gonadotropin-releasing hormone (GnRH), and in normal male sexual behavior by controlling the development of the sexually dimorphic nucleus of the preoptic area (POA). In this study we investigated the effect of NELL2 on the female rat estrous cycle. NELL2 expression in the POA was highest during the proestrous phase. NELL2 mRNA levels in the POA were increased by estrogen treatment in ovariectomized female rats. Blocking NELL2 synthesis in the female rat hypothalamus decreased the expression of kisspeptin 1, an important regulator of the GnRH neuronal apparatus, and resulted in disruption of the estrous cycle at the diestrous phase. These results indicate that NELL2 is involved in the maintenance of the normal female reproductive cycle in mammals.

Mammary stem cells and their regulation by steroid hormones

Sustained exposure to estrogen and progesterone is a well-established risk factor for breast cancer. These hormones play a central role in the female reproductive cycle, in which they control morphogenesis of the mammary gland during puberty, ovulatory cycles and pregnancy. Mouse mammary stem cells (MaSCs) have recently been discovered to be highly responsive to female hormones, despite lacking expression of the estrogen and progesterone receptors. The inhibition of MaSCs by hormone receptor antagonists further suggests that these cells contribute to oncogenesis. Identification of paracrine mediators of hormone signaling to MaSCs may lead to the development of novel inhibitors that drive MaSCs into a more quiescent state. In this context, inhibition of the receptor activator of NF-κB/receptor activator of NF-κB ligand signaling pathway has profound implications for the prevention of breast cancer.

Abstract 4542: Dose-dependent effects of progestins on progesterone receptor activity and target gene expression: less is more

Abstract While the molecular mechanisms by which the progesterone receptor (PR) regulates breast tumor growth and metastasis have not been fully elucidated, recent studies highlight the fact that PR has a complex role in breast cancer progression that may be dependent on ligand dose. For example, data from the Women's Health Initiative trial suggest that low-dose progestins used in combination with estrogen are associated with an increased risk of invasive breast cancer compared to estrogen alone. On the other hand, high-dose progestin therapy has been used as an effective front-line and second-line treatment for advanced, metastatic breast cancer. To investigate this paradox, we undertook studies to identify aspects of PR biology that respond differently to treatment with low or high doses of progestins. Interestingly, we found that treatment of T47D breast cancer cells with low-dose progestins generates a significantly more robust induction of a subset of PR target genes, including the cell cycle regulators cyclin D1 and E2F1, than treatment with high-dose progestins. Furthermore, we show that varying doses of progestins have differential effects on the receptor itself, including the subcellular localization, phosphorylation and subsequent turnover of PR. At the level of transcriptional regulation, our ChIP analyses have led us to hypothesize that the strength of PR activation of target gene expression may hinge upon the ratio of phospho-PR versus unmodified PR that is recruited to enhancer elements. This dose-dependent effect may result in the formation of different PR transcriptional complexes and explain the diverse downstream biologies that are regulated by varying levels of progestins throughout the female reproductive cycle and in diseases such as breast cancer. Given the wide range of medical therapies that utilize progestins, our findings may have important clinical implications. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4542. doi:10.1158/1538-7445.AM2011-4542

Gametogenic Cycle and the Spawning Season by Quantitative Statistical Analysis and the Biological Minimum Size of Cyclina sinensis in Western Korea

The gametogenic cycle and the spawning season in female and male Cyclina sinensis were investigated by quantitative statistical analysis using an image analyzer system, and the biological minimum size (the size at 50% of sexual maturity) was calculated by combination of quantitative data by size and von Bertalanffy's equation. Compared the gametogenic cycle by quantitative statistical analysis with the previous qualitative results in female and male C. sinensis, monthly changes in female and male gametogenic cycles calculated by quantitative statistical analysis showed similar patterns to the gonadal stages in female and male reproductive cycles by qualitative histological analysis. Comparisons of monthly changes in the portions (%) of each area to eight kinds of areas by quantitative statistical analysis in the gonads in female and male C. sinensis are as follows. Monthly changes in the portions (%) of the ovary areas to total tissue areas in females and also monthly changes in the portions of the testis areas to total tissue areas in males increased in March and reached the maximum in May, and then showed a rapid decrease from June to October. Monthly changes in the portions (%) of oocyte areas to ovarian tissue areas in females and also monthly changes in the portions of the areas of the spermatogenic stages to testis areas in males began to increase in March and reached the maximum in June in females and males, and then rapidly dropped from July to October in females and males when spawnig occurred. From these data, it is apparent that the number of spawning seasons in female and male C. sinensis occurred once per year, from July to October. Monthly changes in the number of the oocytes per mm2 and in the mean diameter of the oocyte in captured image which were calculated for each female slide showed a maximum in May and reached the minimum from December to February. Therefore, C. sinensis in both sexes showed a unimodal gametogenic cycle during the year. The percentage of sexual maturity of female and male clams ranging from 25.1 to 30.0 mm in length was over 50% and 100% for clams over 40.1 mm length. In this study, the biological minimum size (sexually mature shell lengths at 50% of sexual maturity) in females and males were 26.85 and 26.28 mm, respectively.

WNT signaling and the regulation of ovarian steroidogenesis

One of the major functions of the ovary is the biosynthesis of steroid hormones, which are essential for the development of secondary sexual characteristics at puberty, for subsequent ovarian function, and for the establishment and maintenance of pregnancy. Increases in our understanding of the molecular mechanisms governing the control of ovarian steroidogenesis have greatly improved our understanding of the female reproductive cycle, as well as the pathogenesis of reproductive disorders such as polycystic ovarian syndrome and premature ovarian failure. The pituitary gonadotropins follicle stimulating hormone (FSH) and luteinizing hormone (LH) are the main endocrine regulators of ovarian steroidogenesis, and act by directly or indirectly modulating the activity of a multitude of intracellular signaling pathways. The WNT/CTNNB1 pathway, which is now believed to be a significant contributor to the regulation of ovarian steroidogenesis, could be one of the pathways modulated by gonadotropin signaling. This review will focus on the emerging role of WNT/CTNNB1 signaling in the regulation of steroidogenesis, with emphasis on potential mechanisms of interaction with FSH/LH signaling in ovarian granulosa and luteal cells.

Can male white-faced saki monkeys (Pithecia pithecia) detect female reproductive state?

Abstract For mammalian males, copulating with females during ovulation is critical to reproductive success. However male knowledge of ovulation may not always be advantageous for females, as it could hinder mate choice or promote harassment. White-faced saki monkeys live in variably monogamous and polygamous social groups and hence females may have multiple motivations to conceal ovulatory timing. White-faced sakis further show no obvious physical or behavioral signs of ovulation, although they do use scent in a variety of contexts, including sexual behavior. We collected data on three wild groups of white-faced sakis at Brownsberg Naturepark, Suriname in order to assess whether male copulations are coordinated with female ovulatory timing. We recorded all occurrences of copulations and genital inspections, and collected fecal samples from females which were radioimmunoassayed to obtain estradiol and progesterone levels. We found that males copulated throughout the female reproductive cycle, although the association between copulation and reproductive state varied between dyads. Only one male–female dyad showed significantly more copulations than expected during ovulation. However four of five dyads copulated less than expected with pregnant females, suggesting that males may be able to differentiate cycling from non-cycling females. While genital inspections were distributed randomly with regard to female reproductive state, the decision to copulate was not: males were more likely to mate with both ovulating and cycling females than with non-cycling females after genital inspection. Regardless, males were not more likely to copulate with an ovulating vs. a cycling (non-ovulating) female. These data indicate that while males may receive olfactory information on female hormonal status, they do not make entirely accurate decisions with regard to copulation timing. This inaccuracy may be due to males' inability to detect ovulation, or alternately a lack of motivation to limit copulations solely to conceptive periods. Pair familiarity and sexual experience may also play a role in copulation accuracy.

Ecology of Southern African Sandveld Lizards (Lacertidae, Nucras)

Sandveld lizards (genus Nucras) are widespread in southern Africa, but are generally secretive and poorly known. We examined 385 preserved specimens from five species of Nucras collected over a broad time span (104 years) and a geographic area covering most of South Africa and Swaziland. We had three main objectives: to test for sexual size dimorphism, to quantify male and female reproductive cycles, and to determine diet. In addition, we examined the importance of scorpions in the diet of Nucras based on previous studies reporting an unusually high incidence of scorpions in the diet of Kalahari N. tessellata. Males of all species except N. lalandii had significantly larger heads than females of the same body size, although females had significantly greater snout–vent length than males in three of the five species examined. The general reproductive pattern was for females to contain vitellogenic eggs during late spring and early summer. No females simultaneously contained oviductal and vitellogenic eggs, which suggests that females produce only one clutch per season. Clutch size was unrelated to female body size in all species examined. Female follicle volume generally coincided with male testicular volume, indicating for the most part synchronized reproductive cycles between the sexes. Testis volume was generally highest during spring–early summer, with only N. holubi showing a second peak in autumn. We recorded 15 arthropod orders in the diet of Nucras. All species feed on invertebrates, primarily insects, and, to a lesser degree, spiders and centipedes. Termites, grasshoppers, and beetles both numerically and volumetrically dominated their diet. We found no evidence that scorpions form a major part of the diet of any of these five species of Nucras, including N. tessellata from biomes outside the Kalahari Desert.

The Fate and Function of Therapeutic Antiaddiction Monoclonal Antibodies across the Reproductive Cycle of Rats

During preclinical development of neuroprotective antiaddiction therapeutic monoclonal antibodies (mAbs) against phencyclidine (PCP) and (+)-methamphetamine, we discovered novel, gestation stage-specific changes in mAb disposition spanning the entire reproductive cycle of female rats. Each pharmacological change was independent of mAb dose and antigen target but was precisely coincident with transitions between the gestational trimesters, parturition, and lactation periods of the female reproductive cycle. Whereas anti-PCP mAb6B5 terminal elimination half-life (t(1/2λz)) in nonpregnant females was 6.6 ± 1.6 days, the mAb6B5 t(1/2λz) significantly changed to 3.7 ± 0.4 days, then 1.4 ± 0.1 days, then 3.0 ± 0.4 days in the second trimester, third trimester, and postpartum periods, respectively (p < 0.05 for each change). Initially, these evolving changes in mAb6B5 clearance (3.3-fold), distribution volume (1.8-fold), and elimination half-life (4.7-fold) affected our ability to sustain sufficient mAb6B5 levels to sequester PCP in the bloodstream. However, understanding the mechanisms underlying each transition allowed development of an adaptive mAb-dosing paradigm, which substantially reduced PCP levels in dam brains and fetuses throughout pregnancy. These mAb functional studies also revealed that antidrug mAbs readily cross the placenta before syncytiotrophoblast barrier maturation, demonstrating the dynamic nature of mAb pharmacokinetics in pregnancy and the importance of maintaining maternal mAb levels. These studies provide the first preclinical pregnancy model in any species for chronic mAb dosing and could have important implications for the use of antibody therapies involving blood organ barriers (such as addiction) or other chronic diseases in women of childbearing age (e.g., irritable bowel diseases, multiple sclerosis, breast cancer, rheumatoid arthritis).