Aging and reproductive potential in women.

Reproductive potential in women declines with age. Age-related changes in the ovary account for most of this loss of reproductive function. Oocytes, all of which are present at birth, decline in number and quality with age. The endocrine function of the ovary also declines with age, and the ovary becomes unable to sustain its normal function in the neuroendocrine axis. The neuroendocrine axis may be further affected by primary changes occurring in the hypothalamus and pituitary during aging, although this has not been established in humans. Aging also affects the function of the uterus as the endometrium loses its ability to support implantation and growth of an embryo. Diminished uterine function during aging may be due to changes in the uterine vasculature or to changes in the hormone-dependent development of the endometrium. Finally, aging increases a woman's risk of developing medical, gynecologic or obstetric conditions that may impair her fertility. Knowledge of these affects of aging on a woman's reproductive function is essential to advise and treat the growing number of women seeking pregnancy at advanced reproductive age.     

Secretory proteins in the reproductive tract of the snapping turtle, Chelhydra serpentina

SDS-polyacrylamide gel electrophoresis was used to separate the secretory proteins produced by the epithelial and endometrial glands of the uterine tube and uterus in the snapping turtle Chelydra serpentina. The proteins were analyzed throughout the phases of the reproductive cycle from May to August, including preovulatory, ovulatory, postovulatory or luteal, and vitellogenic phases. The pattern of secretory proteins is quite uniform along the length of the uterine tube, and the same is true of the uterus, but the patterns for uterine tube and uterus are clearly different. We identify 13 major proteins in C. serpentina egg albumen. Bands co-migrating with 11 of these are found in the uterine tube, but at most 4 are found in the uterus, suggesting that the majority of the albumen proteins are most likely secreted in the uterine tube, not in the uterus. Although some of the egg albumen proteins are present in the uterine tube only at the time of ovulation, most of the bands corresponding to albumen proteins are present throughout the breeding season even though the snapping turtle is a monoclutch species. These results suggest that the glandular secretory phase in the uterine tube is active and quite homogeneous in function regardless of location or phase of the reproductive cycle.     

Unusual membranous network with spines in the uterus of Xiphinema coomansi (Nematoda: Longidoridae)

An ultrastructural study of the uterus of Xiphinema coomansi reveal that the numerous uterine spines present in this species are not anchored to the inner wall of the tubular uterus, but are symmetrically arranged and attached in a membranous network suspended throughout the entire length of the uterus. The spines are solid, hexagonal structures enveloped and connected in tri-radial fashion to each other, as well as to the inner uterine wall by a continuous thin undulating membrane. The network membrane thus formed encloses numerous compartments on the luminal side of the uterus, which seems to create a type of barrier between the plicated uterine wall and a rather constricted central lumen. No such membranous intrauterine network has been reported previously in the reproductive system of nematodes.     

Cryoablation used in fertility-sparing treatment for early endometrial cancer: A pig model experiment using a new designed balloon cryoprobe

Young patients with early endometrial cancer have a strong desire to retain reproductive function, which require us to develop a therapeutic method that can not only assure the complete resection of tumor but also retain the uterine integrity. In the present study, we proposed a fertility-sparing surgery option that combined hysteroscopic resection with cryoablation to achieve this goal. To verify the safety and effectiveness of cryoablation for local uterine wall, we designed the experiment in pig model using a novel cryoablation balloon probe. In the process of freezing and thawing, the temperature of different parts of the uterus was measured in real time. The uterus was harvested immediately, three weeks after cryotherapy for histological evaluation. The results demonstrated cryoablation using the new cryoprobe is safe and effective. The effective freezing range can cover a range of 2 cm in diameter at least. This study provided us evidence before cryoablation could be applied in clinical practice of fertility-sparing treatment for young women with early endometrial cancer.     

Noradrenergic and cholinergic nerves in the uterus of the Japanese long-fingered bat,Miniopterus schreibersii fuliginosus,change with reproductive cycle

The pattern of uterine innervation by noradrenergic (NA) and acetylcholinesterase-positive (AChE) nerves in different reproductive stages of the adult Japanese long-fingered bats were investigated histochemically and immunohistochemically. In the non-pregnant bat, the uterine horn was supplied with abundant NA and AChE nerves. These two types of nerves were closely associated with the uterine arteries and myometrial smooth muscles. In the pregnant bat, NA and AChE nerves supplying the uterus did not degenerate much during hibernating period, but reduced markedly after arousal. In the postpartum bat, the density of nerves recovered progressively. The significant change in the innervation pattern of uterine NA and AChE nerves in the pregnant bats under and after hibernation, and in the postpartum bat must be considered in relation to the adrenergic and cholinergic controlling mechanisms on the uterine function that is matched for the unique reproductive cycle of this bat.     

Disruption of the tissue inhibitor of metalloproteinase-1 gene results in altered reproductive cyclicity and uterine morphology in reproductive-age female mice

Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a multifunctional protein expressed in the uterus of essentially all species, yet the function of this protein is uncertain. To assess the role of TIMP-1 in the uterine events that occur during the murine estrous cycle, mature female TIMP-1 wild-type and null mice were monitored for reproductive cyclicity. Mice were sacrificed in each stage of the estrous cycle, and peripheral blood was collected and assayed for serum estradiol and progesterone content by RIA. Uterine morphology and TIMP-1, TIMP-2, TIMP-3, and TIMP-4 mRNA expression were also examined between genotypes in each stage of the estrous cycle. Disruption of the TIMP-1 gene product was associated with an altered reproductive cycle characterized by a significant decrease in the length of the estrus period in the null mice. Also during the period of estrus, null mice expressed significantly lower levels of uterine TIMP-3 mRNA expression, altered uterine morphology, significantly higher serum estradiol levels, and significantly lower serum progesterone levels compared to their wild-type counterparts. It is concluded from this study that TIMP-1 has a multifaceted role in regulating the murine reproductive cycle, and this control appears to be at the level of both the uterus and the ovary.     

Uterine epithelial-sperm interaction, endometrial cycle and sperm storage in the terminal zone of the oviducal gland in the placental smoothhound, Mustelus canis.

The fate of spermatozoa deposited within the female reproductive tract has been described in the smoothhound, Mustelus canis. Evidence of uterine epithelial-sperm interaction is presented, as well as documentation of sperm storage specifically in the terminal zone of the oviducal gland. Sperm fate is correlated with morphology of the endometrial cycle and specificity of storage in the oviducal gland. The endometrium of M. canis undergoes dramatic tissue remodeling associated with gestation. In females harboring fertilized ova or preimplantation yolk-reliant embryos, the uterine epithelium is simple cuboidal with mucous droplets for lubrication. The presence of the embryo elicits a response from the uterus, which becomes modified for nutrient and respiratory exchange into vascular uterine attachment sites that abut the distal aspect of the yolk sac. Areas of the uterus adjacent to the uterine attachment sites are termed paraplacental sites. Uterine attachment sites are simple squamous while the paraplacental epithelium is simple columnar. Paraplacental cells have basal metachromatic vesicles and a dense array of apical cytoplasmic filaments. Immediately postpartum the uterine attachment sites, now termed uterine or placental scars, begin to remodel to a mucous epithelium for the next gestational cycle. Paraplacental cells slough off the apical filamentous portion, and sperm become embedded in the epithelium. Bundled sperm occur throughout gestation in the terminal zone of the oviducal gland. Sperm are not embedded in the terminal zone epithelium as in the uterus. Following sperm release from the uterus, the paraplacental epithelium reverts to a mucous epithelium for the next reproductive cycle. Fertilization is presumed to occur in the anterior oviduct above the oviducal gland. The physiological mechanisms that mediate sperm-uterus attachment, release, and storage in the terminal zone of the oviducal gland are currently under investigation.     

Anatomy and histology of the reproductive tract of the female Babirusa (Babyrousa celebensis)

The anatomy and histology of the female reproductive tract of the Indonesian wild pig Babyrousa celebensis was studied by means of reproductive tracts obtained from seven animals aged between two and 22 years of age. The ovary appeared to have the ability to ovulate up to four ova at one time. However, the combined ovarian output seemed to average 1.86 ova. Ovulation can take place at any time from puberty to old age (22 years). The opening to the uterine tube was indicated by a ‘flower-like' array of tall, broad epithelial ‘petals' arising from the luminal surface of the funnel. The mucosal surfaces of these structures were covered in a mixture of prominent ciliated cells and bulbous secretory cells. The uterine tube followed a tightly convoluted path to the tip of the uterine horn. The uterus was proportionately short. The anatomical construction of the uterus was similar to those of other suids in that the columnar endometrium was heavily folded, there was a rich supply of uterine glands in the lamina propria, and the uterus was provided with a good blood supply. The cervix was thick walled and had a spiral lumen.     

Molecular mechanisms involved in progesterone receptor regulation of uterine function

The ovarian steroid hormone progesterone is a major regulator of uterine function. The actions of this hormone is mediated through its cognate receptor, the progesterone receptor, Pgr. Ablation of the Pgr has shown that this receptor is critical for all female reproductive functions including the ability of the uterus to support and maintain the development of the implanting mouse embryo. High density DNA microarray analysis has identified direct and indirect targets of Pgr action. One of the targets of Pgr action is a member of the Hedgehog morphogen Indian Hedgehog, Ihh. Ihh and members of the Hh signaling cascade show a coordinate expression pattern in the mouse uterus during the preimplantation period of pregnancy. The expression of Ihh and its receptor Patched-1, Ptc1, as well as, down stream targets of Ihh-Ptch1 signaling, such as the orphan nuclear receptor COUP-TF II show that this morphogen pathway mediates communication between the uterine epithelial and stromal compartments. The members of the Ihh signaling axis may function to coordinate the proliferation, vascularization and differentiation of the uterine stroma during pregnancy. This analysis demonstrates that progesterone regulates uterine function in the mouse by coordinating the signals from the uterine epithelium to stroma in the preimplantation mouse uterus.     

Dominant activation of the hedgehog signaling pathway alters development of the female reproductive tract

The role of hedgehog (HH) signaling in reproductive tract development was studied in mice in which a dominant active allele of the signal transducer smoothened (SmoM2) was conditionally expressed in the Müllerian duct and ovary. Mutant females are infertile, primarily because they fail to ovulate. Levels of mRNA for targets of HH signaling, Gli1, Ptch1, and Hhip, were elevated in reproductive tracts of 24-day-old mutant mice, confirming overactivation of HH signaling. The tracts of mutant mice developed abnormally. The uterine luminal epithelium had a simple columnar morphology in control mice, but in mutants contained stratified squamous cells typical of the cervix and vagina. In mutant mice, the number of uterine glands were reduced and the oviducts were not coiled. Expression of genes within the Hox and Wnt families that regulate patterning of the reproductive tract were altered. Hoxa13, which is normally expressed primarily in the vagina and cervix, was expressed at 12-fold higher levels in the uterus of mutant mice compared with controls. Wnt5a, which is required for development of the cervix and vagina and postnatal differentiation of the uterus, was expressed at higher levels in the oviduct and uterus of mutant mice compared with controls. Mating mutant females with fertile or vasectomized males induced a severe inflammatory response in the tract. In summary, overactivation of HH signaling causes aberrant development of the reproductive tract. The phenotype observed could be mediated by ectopic expression of Hoxa13 in the uterus and elevated levels of Wnt5a in the oviducts and uterus.     

Calcium ATPase expression in the oviducts of the skink, Lampropholis guichenoti

Lampropholis guichenoti is an oviparous lizard that lays eggs with a calcareous outer shell. We used immunofluorescence microscopy to describe the occurrence and distribution of Ca2+ ATPase pumps in the uterus of L. guichenoti at different stages of the reproductive and egg-shelling cycles. Ca2+ ATPase pumps were not demonstrated by immunofluorescent techniques in any uterine tissue until egg-shelling had commenced and at least partly calcified eggs were in the uterus. During egg-shelling, Ca2+ ATPase pumps occur on the apical and baso-lateral surfaces of uterine epithelial cells, and those of associated shell glands in the stroma of the uterus. We conclude that Ca2+ ATPase pumps provide a major mechanism for deposition of the calcareous eggshell of L. guichenoti and that the pumps are up-regulated when required in the reproductive cycle. Furthermore, it is likely that specific calcium glands in the stroma of the uterus are involved in the rapid transport required for egg-shelling, but the differential contribution of luminal and glandular epithelial cells is not known.     

Depression of estrogen-induced uterine peroxidase in alloxan-diabetic rats

The influence of alloxan diabetes on reproductive function and the estradiol-stimulated increase in uterine peroxidase was investigated. Alloxan monohydrate in a dose of 75 mg/kg body weight effectively produced permanent diabetes. In adult rats, 20 days of diabetes resulted in cessation of the estrous cycle and a significant reduction in the gain of body weight, the weights of anterior pituitary gland, ovary, uterus, the level of serum progesterone and the activity of the estradiol-stimulated uterine peroxidase (P less than 0.05). After 10 days of insulin treatment, the ovarian weight, the estrous cycle and the level of ovarian hormones were restored to normal whereas the uterine weight and the estradiol-stimulated uterine peroxidase activity were only partially recovered. Persistent depression of the uterine response in the insulin-treated diabetic rats to both endogenous and exogenous ovarian hormone stimulation suggests that the uterus was directly affected by diabetes. The direct effect of diabetes upon the uterus was further demonstrated in the ovariectomized immature rat in which diabetes depressed the stimulatory action of estradiol on both uterine weight and uterine peroxidase activity.     

Comparative morphology and evolution of the female reproductive tract in macroglossine bats (mammalia,chiroptera)

Comparative morphological analysis of the female reproductive tract in macroglossine bats was undertaken to test the hypothesis that nectarivory arose at least twice within Old World fruit bats. Given that features of the female reproductive tract are not directly involved in adaptations for feeding, this data set should provide a test of the monophyly of macroglossine bats. A cladistic analysis of variation in the structure of the ovaries, oviducts, uterus, and external genitalia supports the hypothesis that Megaloglossus has developed a nectar-feeding habit independent of other macroglossine genera. Most of the variation in female reproductive organs among pteropodids is found in the development of derived external and internal features of the uterus. Fusion of uterine cornua, expansion of the common uterine body, and elaboration of the cervical region are found in a group which includes species of Pteropus, Dobsonia, Nyctimene, and the macroglossines (excluding Megaloglossus). Results of this study are concordant with independent data sets, thus providing a phylogenetic framework to evaluate critically structural and functional design in the evolution of pteropodid feeding mechanisms.     

A histochemical study of the secretions of reproductive glands and of the egg envelopes of Achatina fulica (Pulmonata: Stylommatophora)

Histochemical investigations of the secretions of reproductive glands—albumen gland, apical uterus, basal uterus and prostate gland—indicate the presence of galactogen in the albumen gland, acid mucopolysaccharide in the apical uterus, and lipoprotein in the basal uterus and prostate gland of A. fulica. The proteinaceous secretions produced by the glands do differ in their terminal reactive sites. Intense alkaline phosphatase reaction is found in albumen gland and apical uterus; carbonic anhydrase activity could be detected mainly in the uterine glands. The cyclical secretory activity of the reproductive glands has been studied preparatory to egg-laying and in the spent phase. Histochemical characteristics of the egg envelopes—albumen, shell membrane and egg-shell—suggest a possible sequential deposition of glandular products during the descent of eggs through the repv. ductive tract. The factors contributing to the stability and resistant nature of the egg envelopes, and the possible role of nutritive materials contained in reproductive gland secretions in the development of the embryo (even while the eggs are inside the uterus), are discussed.     

Reproductive Aging Drives Protein Accumulation in the Uterus and Limits Lifespan in C. elegans

Aging in Caenorhabditis elegans is characterized by widespread physiological and molecular changes, but the mechanisms that determine the rate at which these changes occur are not well understood. In this study, we identify a novel link between reproductive aging and somatic aging in C. elegans. By measuring global age-related changes in the proteome, we identify a previously uncharacterized group of secreted proteins in the adult uterus that dramatically increase in abundance with age. This accumulation is blunted in animals with an extended reproductive period and accelerated in sterile animals lacking a germline. Uterine proteins are not removed in old post-reproductive animals or in young vulvaless worms, indicating that egg-laying is necessary for their rapid removal in wild-type young animals. Together, these results suggest that age-induced infertility contributes to extracellular protein accumulation in the uterus with age. Finally, we show that knocking down multiple age-increased proteins simultaneously extends lifespan. These results provide a mechanistic example of how the cessation of reproduction contributes to detrimental changes in the soma, and demonstrate how the timing of reproductive decline can influence the rate of aging.     

Morphology and ultrastructure of reproductive organs of <Emphasis Type="Italic">Monocercus arionis</Emphasis> (Sibold, 1850) Villot, 1982 (Cestoda: Cyclophyllidea)

The morphology of the reproductive system at different stages of ontogenesis and ultrastructural peculiarities of the copulatory organs and uterine in Monocercus arionis (Sibold, 1850) Villot, 1982 (Cyclophyllidea) have been studied. The muscle of the outer wall of the cirrus bag has a higher organizational level than typical smooth-muscle cells in cestodes. The cirrus is armed with typical filamentous and bladelike microtriches. The uterine epithelium contacts the thin capsule of the developing embryos located closely to the uterus wall, and the embryos contact each other in the uterine cavity in what can be interpreted as placental interactions. The specificity of the structure and arming of the copulatory apparatus has been considered, and the ultrastructural peculiarities of the uterus in the members of different orders of cestodes have been compared and analyzed.     

Alligators provide evidence for the evolution of an archosaurian mode of oviparity.

The female reproductive tract of birds is different from that of other oviparous amniotes in that the eggshell membranes and calcareous layer are formed in separate regions of the uterus; the isthmus and shell gland, respectively. Phylogenetically, birds are included among the archosaurs, along with crocodilians and dinosaurs. Many dinosaurs were oviparous, producing hard-shelled eggs, yet the reproductive system of dinosaurs has proven difficult to investigate, due to poor preservation of soft anatomy. In this study, we examined functional morphology and eggshell formation in a reptilian archosaur, the American alligator, and demonstrated that the crocodilian reproductive tract has separate uterine regions for formation of the eggshell membranes and calcareous layer. These uterine regions are ultrastructurally comparable to the isthmus and shell gland of birds, and may be homologous. This similarity of reproductive functional morphology between crocodilians and birds may implicate the evolution of an archosaurian mode of oviparity that may shed light on dinosaur reproduction.