Hirohiko Watanabe

Bcl-2 and Fas expression in eutopic and ectopic human endometrium during the menstrual cycle in relation to endometrial cell apoptosis

OBJECTIVEnOur purpose was to investigate Bcl-2 and Fas expression in human eutopic and ectopic endometrium during the menstrual cycle in relation to endometrial cell apoptosis.nnnSTUDY DESIGNnEutopic and ectopic endometrial samples were obtained from 29 patients with endometriosis, and eutopic endometrial tissue samples were obtained from 9 patients with uterine myoma. Bcl-2 and Fas expression were examined by immunohistochemical staining with specific monoclonal antibodies; Bcl-2 expression in eutopic endometrium was also examined by Western blotting and apoptotic cells were detected by the labeling of deoxyribonucleic acid fragments.nnnRESULTSnIn eutopic endometrium Bcl-2 was strongly expressed during the proliferative phase. Endometrial glandular cells showed evidence of cyclic changes in Bcl-2 expression, but cyclic changes were not apparent in peritoneal and ovarian endometriotic tissue. Fas expression was observed on glandular cells but not on stromal cells, and no cyclic changes in expression occurred in either ectopic or eutopic endometrium. Apoptotic cells were observed primarily in the glandular cells of the basal layer in eutopic endometrium during the late secretory and menstrual phases.nnnCONCLUSIONnThe current study indicated that there was no apparent correlation between Bcl-2 or Fas expression with endometrial cell apoptosis. The absence of cyclic changes in Bcl-2 expression in ectopic endometrium implied a difference in the mechanisms of proliferation or differentiation between eutopic and ectopic endometrium.

Adiponectin and its receptors modulate granulosa cell and cumulus cell functions, fertility, and early embryo development in the mouse and human.

OBJECTIVEnTo study the expression and function of adiponectin and its receptors in mouse and human follicle cells and in early embryo development.nnnDESIGNnWhole ovaries, granulosa cells, and cumulus-oocyte complexes isolated from immature mice before and during hormone-induced ovulation were used to analyze the expression of adiponectin, its receptors, and ovulation-related genes; human cumulus cells and granulosa cells were isolated from patients undergoing in vitro fertilization (IVF) procedures.nnnSETTINGnMulticenter.nnnPATIENT(S)nWomen in IVF programs in Japan and the United States.nnnINTERVENTION(S)nNone.nnnMAIN OUTCOME MEASURE(S)nExpression of adiponectin receptors and fertility.nnnRESULT(S)nAdiponectin expression is absent/low in mouse and human granulosa cells and cumulus cells. Adiponectin receptors are hormonally regulated in mouse granulosa and cumulus cells in vivo and in culture. Adiponectin differentially alters the expression of Adipor1/Adipor2 as well as genes related to steroidogenesis, ovulation, and apoptosis in cumulus cells versus granulosa cells. Adiponectin enhances oocyte maturation and early embryo development in mouse and human IVF procedures.nnnCONCLUSION(S)nAdiponectin can modulate not only follicle growth but also embryo development in mice and humans.

Assessment of human oocyte developmental competence by cumulus cell morphology and circulating hormone profile

The predictive value of the morphology of the cumulus--oocyte complex (COC) has not yet been explored as a possible factor contributing to the success of human in-vitro maturation (IVM). In the present study, development-supporting competency of oocytes encircled in a large ( > or = 5) (grade A), moderate (3 approximately 4) (grade B) or small ( < or = 2) (grade C) number of cumulus cell layers was assessed, together with changes in hormonal profile following a truncated course of 150 IU pure FSH administration for 3 days prior to aspiration on laparoscopy indicated for endometriosis. FSH priming increased the number of COC aspirated without changing the proportion of the three morphological types of COC, which were then subjected to IVM in the presence of 200 mIU/ml FSH plus 1000 mIU/ml human chorionic gonadotrophin, followed by intracytoplasmic sperm injection. The highest development-supporting competence was observed not with oocytes in grade A COC harvested from natural cycles, but with oocytes in grade B COC from FSH-primed cycles. Hormonal profiles in patients bearing grade B COC were characterized by moderate response in oestradiol and progesterone production following FSH, with LH/FSH ratio being below 1.0. It is concluded that an optimal window of hormonal profile(s) may exist for follicle aspiration to obtain grade B COC in FSH-stimulated human IVM cycles.

Expression of Apg-1, a member of the Hsp110 family, in the human testis and sperm

Apg‐1 encodes a heat shock protein belonging to the Hsp110 family and is inducible by a 32°C to 39°C heat shock in somatic cells. In mouse testicular germ cells Apg‐1 mRNA is constitutively expressed depending on the developmental stage. As human Apg‐1 has recently been identified, the expression of Apg‐1 in the human testis and sperm was investigated.

Human leukocyte antigen may predict outcome of primary recurrent spontaneous abortion treated with paternal lymphocyte alloimmunization therapy.

Recurrent spontaneous abortion (RSA) is defined by at least three consecutive abortions in otherwise healthy couples. Paternal lymphocyte alloimmunization therapy (PLAT) is an effective therapy for RSA in some cases, but there are no predictive markers about the effectiveness of PLAT.

Developmentally retarded frozen blastocysts can be rescued by synchronizing culture prior to transfer

Asynchrony between embryo development and endometrial differentiation is the limiting step of successful pregnancy in assisted reproduction. The aim of this study was to investigate whether or not post-thaw synchronization culture of day 5-6 frozen embryos, prior to transfer, with endometrial differentiation resulted in pregnancy. A total of 142 cycles of 134 patients were transferred in three protocols. Blastocysts with cavities larger than half of the entire blastocyst volume were transferred without synchronizing culture on day 5 or 6 of progesterone commencement (P5/6) in hormone replacement treatment cycles (protocol 1). Blastocysts with cavitation below half of the entire blastocyst were cultured for 1 or 2 days after thawing prior to transfer on P5 or P6 (protocol 2). Morulae and very early stage blastocysts were thawed on the days corresponding to P5 and P6, and only the embryos that reached expanded or hatching blastocysts were transferred on P7 without synchronizing culture (protocol 3). Pregnancy rate in protocol 2 (32.0%) was comparable with that of protocol 1 (35.0%). It is concluded that developmentally retarded frozen embryos can be rescued with synchronizing culture prior to transfer by evading asynchrony.

Morphogenesis of polycystic ovaries as assessed by pituitary–ovarian androgenic function

Despite polycystic ovaries (PCO) being a common morphology in women with polycystic ovary syndrome and regular menstruation, the regulatory principles in the morphogenesis of antral follicles have not yet been elucidated. In recognition of the complementary interaction between androgen-induced expression of the FSH receptor and FSH-augmented expression of the androgen receptor in granulose cells of antral follicles, a possible correlation of antral follicle count (AFC) and pituitary-ovarian androgenic function was investigated in 180 infertile women over days 3-5 of the menstrual cycle. Six discrete types of PCO with decreasing pituitary-ovarian androgenic function were identified: Type I (classical Stein-Leventhal syndrome), Type II (hyperandrogenemism), Type III (singular hyper-LH), Type IV (cryptic hyperandrogenism), Type V (relative LH dominancy) and Type VI (relative FSH dominancy), in parallel to a diminishing number of AFC from Type I to Type VI. Because during the early follicular phase of the cycle until the selection of the dominant follicle, antral follicles are composed of newly emerged healthy follicles plus atretic antral follicles that remain non-ovulated from previous cycles, it is proposed that the six types of PCO may represent the folliculogenetic spectra along which PCO morphogenesis proceeds.

Ethical considerations on indications for gender selection in Japan.

Gender selection is a matter of great concern to a cohort of parents. To what extent the methods available are ethically acceptable at present differs depending upon the society and times the couples live in. In the present communication, the current situation in Japan in use for gender selection by empirical methods without sperm separation, conventional methods with sperm separation and preimplantation genetic diagnosis of human embryos has been provided and considered in the light of human dignity as well as human right.