Reproductive System and Mammary Gland
Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard in Toxicologic Pathology, 2018
The smallest follicles, the primordial follicles, are generally located in the outer portion of the cortex and consist of a small oocyte, arrested at the dictyate stage of meiosis I, encircled by a single layer of flattened, pre-granulosa cells and an outer basal lamina. The factors maintaining the primordial follicles in their arrested state of development are not well understood. During each estrous cycle, a small cohort of primordial follicles is “activated” and begins to enlarge as primary follicles; growth of the oocytes is initiated and the pre-granulosa cells become cuboidal, begin to display receptors for FSH, and start to proliferate. This continued growth results in secondary follicles, which have two or more layers of granulosa cells that encircle the enlarging oocyte. A thick coat of glycoproteins (the zona pellucida) separates the oocyte and adjacent granulosa cells (Wassarman et al. 1999). In response to factors released by the growing follicle, elongated cells recruited from the surrounding stroma form a sheath, the theca, outside of the follicular basement membrane (Magoffin 2005). Those cells nearest the follicular basement membrane, the theca interna, exhibit ultrastructural features of steroid-secreting cells consistent with their role in androgen production. The outermost thecal cells, the theca externa, in contrast are a loosely organized band of non-steroidogenic cells with ultrastructural features of fibroblasts and smooth muscle cells (Magoffin 2005; O’Shea 1981; Young and McNeilly 2010).
The Signaling between Embryo and Mother as a Basis for the Development of Tolerance
Howard J.A. Carp in Recurrent Pregnancy Loss, 2020
In mammalian gestation, immunologic acceptance and tolerance are paramount for the successful interaction between the embryo/graft and its maternal host. Initial immunologic awareness must take place prior to implantation. The semipermeable zona pellucida forms rapidly post fertilization and protects the embryo until it reaches the endometrium. The zona is surrounded by maternal immune cells, and this unit transmits the message that fertilization has occurred. However, in in vitro fertilization (IVF) and embryo transfer this mechanism is not operative. The main question is when and how the embryo-maternal communication initiates and creates maternal recognition of pregnancy. Advances in assisted reproduction suggest that the embryo is the dominant element in the reproductive process; its viability and ability to signal are critical for embryo-maternal recognition. Furthermore, genetics does not appear to play a predominant role; donor embryos or xeno-transfer embryos fare very well following transfer with no discernable difference to semi-allogenic embryos.
Multiple gestation
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
The vast majority of MZ conceptions result in singleton birth. In only a small fraction of the cases (0.4% of all natural conceptions), the zygote splits to form an MZ twin gestation. Available hypotheses proposed to explain the mechanism of zygotic splitting fail to explain why MZ twins are more prevalent after all methods of assisted reproduction (3) and which structure is likely to control this phenomenon. It was hypothesized (4) that a small proportion of oocytes might have an inborn propensity to undergo splitting upon fertilization leading to the constant prevalence of spontaneous MZ twins among different populations. Ovarian stimulation—the common denominator of all infertility treatments—would then predictably increase the number of available splitting-prone oocytes and as a result would increase the chance for such oocytes to develop upon fertilization into MZ twins. An intact zona pellucida seems to be required to control embryonic division into two distinct cell lines and to prevent ill-timed hatching. Human fertilized oocytes are able to undergo binary fissions, just as in the nine-banded armadillo (the only other mammal that produces MZ quadruplets), and to produce a variety of combinations of MZ pregnancies. Importantly, this hypothesis does not negate previous genetically sound hypotheses, but places them into a broader perspective in light of observations from modern infertility treatment (4).
Protein transduction domain of translationally controlled tumor protein: characterization and application in drug delivery
Published in Drug Delivery, 2022
Jeehye Maeng, Kyunglim Lee
Delivery of siRNA using TCTP-PTD across zona pellucida (ZP) in mouse oocytes was reported by Jeon et al (Jeon et al., 2019). The zona pellucida, a glycoprotein matrix that surrounds the biological membranes of embryos and oocytes, limits the permeation of exogenous molecules into mammalian embryos and oocytes during prolonged in vitro culture (Wassarman, 2008; Gupta et al., 2012). This group previously found that overexpression of TCTP can attenuate the time-dependent quality deterioration and apoptosis of oocytes (Jeon et al., 2017). Here, the exogenous TCTP, a form of recombinant TCTP-mCherry, also relieved the quality decline of oocytes when added to culture media, which in turn improved the fertilization capacity and subsequent development of early embryos (Jeon et al., 2019). TCTP-mCherry protein devoid of PTD showed impermeability, confirming the PTD-dependent translocation of TCTP.
Chronic cholestasis is associated with hypogonadism and premature ovarian failure in adult rats (cholestasis causes ovarian hypogonadism)
Published in Ultrastructural Pathology, 2018
Yomna I. Mahmoud
Transmission electron microscopy: Ultrastructural assessment revealed that the ovaries of Sham-operated rats showed no morphological defects. The ovarian surface epithelium consisted of a single layer of cuboidal cells resting on a basal lamina. These cells contained apical microvilli, numerous mitochondria, and large oval and indented nuclei (Figure 4a). Early antral follicles had distinct structural components including the theca externa, theca interna, granulosa cells, and an oocyte. The thecal cells were relatively thin, displaying flattened cells that had elongated spindle-shaped nuclei (Figure 4b). Granulosa cells were arranged in several layers. The basal layer was composed of tall cells resting on a basal lamina (Figure 4b). Other granulosa cells appeared cuboidal with abundant mitochondria, relatively thin cytoplasm and centrally located, ovoid in shape but often indented, euchromatic nucleus (Figure 4c). The inner layer of granulosa cells has thick prolongations that penetrate a smooth and relatively wide zona pellucida. The membrane of the oocyte showed numerous microvilli also penetrating the zona pellucida (Figure 4d). The ooplasm was populated with loosely clustered organelles. Mitochondria appear round or oval, rather dark with small numbers of shelf-like cristae. Cytoplasmic lamellae and electron-lucent vesicular bodies were dispersed throughout the cytoplasm (Figure 4e).
Comparison of the pregnancy and obstetric outcomes between single cleavage-stage embryo transfer and single blastocyst transfer by time-lapse selection of embryos
Published in Gynecological Endocrinology, 2019
Shanshan Wang, Lei Chen, Junshun Fang, Weihua Jiang, Ningyuan Zhang
Several reported findings suggest that delayed transfer of the embryo in the blastocyst stage could have an effect on embryo and fetal development, such as increasing monozygotic twining rates [9,15]. With significantly higher perinatal morbidity and mortality rates than dizygotic twins, monozygotic twins may further affect the safety of mother and baby including pregnancy complications, premature birth, twin transfusion syndrome, and birth weight loss. The results of this study indicated that the incidence of MZT in the SBT group was significantly higher than that in SCT group (6.90% versus 0), which were consistent with the above findings. Possible explanations for the increased incidence of MZT rates of SBT were as follows [16,17]. Firstly, in vitro culture conditions may harden the zona pellucida (ZP) of embryos. The hardening of ZP presumably stimulate the splitting of the inner cell mass (ICM) and thus the production of two identical twins. Prolonged culture to the blastocyst stage in sequential medium may directly affect the adhesion between ICM cells and further make an embryo more susceptible to MZT. In addition, MZT of SBT may be related to the effect on ICM induced by higher glucose content and calcium imbalance in sequential culture media.