Telocytes damage in endometriosis‐affected rat oviduct and potential impact on fertility

Women with endometriosis (EMs) have unexplained infertility. The recently identified telocytes (TCs) might participate in the maintenance of structural and functional integrity of oviduct tissue, but so far the involvement of TCs in EMs‐affected oviduct tissue and potential impact on fertility capacity remain unknown. By an integrated technique of haematoxylin and eosin staining, in situ immunohistochemistry and double‐labelled immunofluorescence staining and electron microscopy approach, TCs were studied in the autotransplantation Sprague–Dawley rat model of EMs‐affected oviduct tissue and in sham control, respectively, together with determination of iNOS, COX‐2, LPO and estradiol. TCs were found in perivascular connective tissue and smooth muscle bundles in sham oviduct, with typical ultrastructural features (a slender piriform/spindle/triangular cell body, and one or more extremely long prolongations, emerged from cell bodies and extend to various directions), and specific immunophenotype of CD34‐positive/vimentin‐positive/c‐kit‐negative. However, in EMs‐affected oviduct tissue (grade III), extensive ultrastructural damage (degeneration, discontinue, dissolution and destruction), significant decrease or loss of TCs and interstitial fibrosis were observed, together with elevated level of iNOS, COX‐2, LPO and estradiol, thus suggestive of inflammation and ischaemia‐induced TCs damage. Based on TCs distribution and intercellular connections, we proposed that such damage might be involved in structural and functional abnormalities of oviduct, such as attenuated intercellular signalling and oviduct contractility, impaired immunoregulation and stem cell‐mediated tissue repair, 3‐D interstitial architectural derangement and tissue fibrosis. Therefore, TCs damage might provide a new explanation and potential target for EMs‐induced tubal damage and fertility disorders.     

Effect of hormonal status and metabolic changes of restricted ewes during late pregnancy on their fetal growth and development

This study investigated the effects of hormonal status and metabolic changes of restricted ewes during late pregnancy on the ovine fetus growth and development. One hundred Mongolian ewes, synchronized for oestrus and mated, were divided into three groups and offered 0.175 MJME·kgw^−0.75·d⁻¹ (Restricted Group 1, RG1), 0.33 MJME·kgw^−0.75·d⁻¹ (Restricted Group 2, RG2) and ad libitum access to feed (Control Group, CG) during their late pregnancy respectively. The results suggested that with the supply of exogenous energy decreasing during late pregnancy, maternal body weight and net body weight loss in RG2 and RG1 were lower than those of CG (Ps0.01). The insulin and IGF-1 concentrations of ewes in RG2 and RG1 tended to be lower than those of CG (P>0.05), but the GH concentrations in RG2 and RG1 were enhanced and there was significant difference between RG1 and CG on d 120 of gestation (P<0.05). The glucose concentration of ewes in RG2 and RG1 was decreased throughout the feed restriction period, and the differences were observed between RG1 and CG on d 120 of gestation (P<0.05). In addition, the nonesterified fatty acid (NEFA) and total amino acid (TAA) concentrations of ewes in RG2 tended to increase, but there was no significant difference (P>0.05). However, the NEFA and FAA concentrations of ewes in RG1 were reduced from d 90 to d 120 of gestation, then enhanced from d 120 to d 140 of gestation. During the late pregnancy, with the supply of nutrition decreasing, the negatively physiological and biochemical maternal reactions to restriction became worse, which significantly reduced the average lamb birth weight and daily growth rate of fetus in RG2 (P<0.05) and RG1 (P<0.01).     

SHOULD RAPID TESTS FOR HIV INFECTION NOW BE MANDATORY DURING PREGNANCY? GLOBAL DIFFERENCES IN SCARCITY AND A DILEMMA OF TECHNOLOGICAL ADVANCE

Since testing for HIV infection became possible in 1985, testing of pregnant women has been conducted primarily on a voluntary, 'opt-in' basis. Faden, Geller and Powers, Bayer, Wilfert, and McKenna, among others, have suggested that with the development of more reliable testing and more effective therapy to reduce maternal-fetal transmission, testing should become either routine with 'opt-out' provisions or mandatory. We ask, in the light of the new rapid tests for HIV, such as OraQuick, and the development of antiretroviral treatment that can reduce maternal-fetal transmission rates to <2%, whether that time is now. Illustrating our argument with cases from the United States (US), Kenya, Peru, and an undocumented Mexican worker in the US, we show that when testing is accompanied by assured multi-drug therapy for the mother, the argument for opt-out or mandatory testing for HIV in pregnancy is strong, but that it is problematic where testing is accompanied by adverse events such as spousal abuse or by inadequate intrapartum or follow-up treatment. The difference is not a 'double standard', but reflects the presence of conflicts between the health interests of the mother and the fetus--conflicts that would be abrogated by the assurance of adequate, continuing multi-drug therapy. In light of these conflicts, where they still occur, careful processes of informed consent are appropriate, rather than opt-out or mandatory testing.     

The effect of hypoxia in development

There is increasing evidence that the oxygen supply to the human embryo in the first trimester is tightly controlled, suggesting that too much oxygen may interfere with development. The use of hypoxia probes in mammalian embryos during the organogenic period indicates that the embryo is normally in a state of partial hypoxia, and this may be essential to control cardiovascular development, perhaps under the control of hypoxia-inducible factor (HIF). A consequence of this state of partial hypoxia is that disturbances in the oxygen supply can more easily lead to a damaging degree of hypoxia. Experimental mammalian embryos show a surprising degree of resilience to hypoxia, with many organogenic stage embryos able to survive 30-60 min of anoxia. However, in some embryos this degree of hypoxia causes abnormal development, particularly transverse limb reduction defects. These abnormalities are preceded by hemorrhage/edema and tissue necrosis. Other parts of the embryo are also susceptible to this hypoxia-induced damage and include the genital tubercle, the developing nose, the tail, and the central nervous system. Other frequently observed defects in animal models of prenatal hypoxia include cleft lip, maxillary hypoplasia, and heart defects. Animal studies indicate that hypoxic episodes in the first trimester of human pregnancy could occur by temporary constriction of the uterine arteries. This could be a consequence of exposure to cocaine, misoprostol, or severe shock, and there is evidence that these exposures have resulted in hypoxia-related malformations in the human. Exposure to drugs that block the potassium current (IKr) can cause severe slowing and arrhythmia of the mammalian embryonic heart and consequently hypoxia in the embryo. These drugs are highly teratogenic in experimental animals. There is evidence that drugs with IKr blockade as a side effect, for example phenytoin, may cause birth defects in the human by causing periods of embryonic hypoxia. The strongest evidence of hypoxia causing birth defects in the human comes from studies of fetuses lacking hemoglobin (Hb) F. These fetuses are thought to be hypoxic from about the middle of the first trimester and show a range of birth defects, particularly transverse limb reduction defects.     

Deep genealogical history without population differentiation: discordance between mtDNA and allozyme divergence in the zebra-tailed lizard (Callisaurus draconoides)

The peninsula of Baja California has a complex geological history that has strongly affected the regional biota. Genealogical histories of many species have revealed congruent patterns, which suggest that the peninsula was temporarily submerged at two locations. We sequenced a total of 1953 base pairs (bp) of the mitochondrial genome for 42 specimens of the zebra-tailed lizard (Callisaurus draconoides). The resulting maternal genealogy supports the former existence of a mid-peninsular seaway and a Plio-Quaternary seaway across the Isthmus of La Paz. In addition, a genealogical break is revealed in the vicinity of Loreto. This genealogical break may have resulted from prolonged submergence of the Loreto Basin during Pliocene. The mid-peninsular seaway may have occurred as early as late Miocene, at a time significantly earlier than previously hypothesized. Comparison with other genealogies and geological evidence suggests that current models on the evolution of Baja California's fauna are temporally shallow. The deep genealogical patterns of C. draconoides also disagree with the very limited population differentiation previously reported for allozyme markers, suggesting that maternal history may not be an appropriate approximation for population differentiation.     

Oxidative stress promotes the increase of matrix metalloproteinases-2 and -9 activities in the feto-placental unit of diabetic rats

Maternal diabetes increases the risk of congenital malformations, placental dysfunction and diseases in both the neonate and the offspring's later life. Oxidative stress has been involved in the etiology of these abnormalities. Matrix metalloproteases (MMPs), involved in multiple developmental pathways, are increased in the fetus and placenta from diabetic experimental models. As oxidants could be involved in the activation of latent MMPs, we investigated a putative relationship between MMPs activities and oxidative stress in the feto-placental unit of diabetic rats at midgestation. We found that H₂O₂ enhanced and that superoxide dismutase (SOD) reduced MMPs activities in the maternal side of the placenta and in the fetuses from control and diabetic rats. MMPs were not modified by oxidative status in the fetal side of the placenta. Lipid peroxidation was enhanced in the maternal and fetal sides of the placenta and in the fetus from diabetic rats when compared to controls, and gradually decreased from the maternal placental side to the fetus in diabetic animals. The activities of the antioxidant enzymes SOD and catalase were decreased in the maternal placental side, catalase activity was enhanced in the fetal placental side and both enzymes were increased in the fetuses from diabetic rats when compared to controls. Our data demonstrate changes in the oxidative balance and capability of oxidants to upregulate MMPs activity in the feto-placental unit from diabetic rats, a basis to elucidate links between oxidative stress and alterations in the developmental pathways in which MMPs are involved.     

Diverse patterns of poly(A) tail elongation and shortening of murine maternal mRNAs from fully grown oocyte to 2-cell embryo stages

We previously succeeded in constructing a cDNA library, CPF7, enriched with cDNA derived from maternal RNAs with the extended poly(A) tail in mouse fertilized eggs. In this study, we performed RNA blot analysis to examine the elongation in maternal RNAs using 20 representative clones isolated from CPF7 as probes. Various patterns of elongation, shortening, and/or degradation of maternal RNAs were observed from fully grown oocytes to early 2-cell embryos and could be roughly classified into three types and seven subtypes. These findings indicate that poly(A) elongation and shortening of maternal RNAs are not restricted to certain types of maternal RNAs but occur in many of them, and suggest a complex mechanism governing modification of the 3' end of maternal RNAs during the oocyte-to-embryo transition.     

Estradiol receptor-alpha expression in hypothalamic and limbic regions of ewes is influenced by physiological state and maternal experience

The influence of estrus, pregnancy, parturition, and maternal experience on the expression of estrogen receptor-alpha (ERalpha) was investigated in hypothalamic and limbic regions of the sheep brain, using immunocytochemistry. Four days before parturition, previous maternal experience was associated with a higher density of ERalpha-labeled neurons in the paraventricular and supraoptic nuclei, the medial preoptic area, and the medial amygdala, but not in the mediobasal hypothalamus. Furthermore, an interaction was found between physiological state and experience in the peripartum period as the effect of experience existing 4 days prepartum was not found at parturition, when densities were lowest both in primiparous and in multiparous ewes. An additional effect of physiological state was also observed between parturition and estrus, densities being significantly lower at parturition than at estrus in the SON, PVN, and MPOA, but not in the medial amygdala. These results indicate that in sheep ERalpha expression is influenced by previous physiological and/or maternal experience at specific times of the reproductive cycle. They are also congruent with the higher ability of multiparous than nulliparous ewes to show maternal behavior several days prepartum.     

Opportunistic mothers: female marmosets (Callithrix kuhlii) reduce their investment in offspring when they have to, and when they can

All female primates incur energetic costs associated with producing and caring for offspring, but females belonging to the New World primate family Callitrichidae, the marmosets and tamarins, appear to face even further demands. In fact, the energetic demands of rearing callitrichid infants are thought to have led to the evolution of cooperative infant care in these species. If this explanation is true, then one might expect that natural selection should also have shaped patterns of maternal behavior to be sensitive to the costs of reproduction and equipped females to reduce their investment in offspring under certain conditions. Therefore, we examined the maternal effort and postpartum endocrine profiles of individual female marmosets (Callithrix kuhlii) across conditions that represented two hallmarks of callitrichid reproduction-conception during the early postpartum period and alloparental assistance. When females conceived during the early postpartum period and faced the upcoming demands of caring for their newly conceived litters (Study 1), they significantly reduced their caregiving effort and had significantly higher postpartum levels of estradiol relative to breeding attempts in which conception occurred later in the postpartum period. Postpartum estradiol was negatively correlated with maternal carrying effort. When experienced alloparents were present (Study 2), females again reduced their caregiving effort relative to breeding attempts in which experienced alloparents were not present. Postpartum cortisol, however, did not vary as a function of experienced alloparental assistance. The results of these studies suggest that female marmosets have been subjected to similar selection pressures as females of other primate taxa--to maximize their reproductive success by reducing their investment in offspring under the worst and best of conditions--and suggest that hormones may mediate within-female variation in maternal care. These studies also provide support for the notion that mothers are "flexible opportunists" when it comes to providing care to their young.